Podcasts about tysabri

I recently enjoyed speaking with the incredible Dr. Summer about her remarkable story. I've been following her journey on TikTok, and I was eager to dive into her experiences with neuromyelitis optica (NMO), a condition that was initially misdiagnosed as multiple sclerosis (MS). Summer's resilience and determination to overcome her challenges are truly inspiring.In the first part of a two-part interview, Summer shared her journey from being misdiagnosed with MS to receiving the correct diagnosis of NMO. She explained that NMO is often confused with MS due to their similarities, but it has distinct characteristics that can lead to more severe symptoms. Summer described her initial experiences with various treatments, including Gilenya and Tysabri, and how they didn't work for her condition. It was only after multiple attacks that her doctors reconsidered her diagnosis and adjusted her treatment plan.During our conversation, we discussed Dr. Summer's journey through misdiagnosis and the impact of her condition on her medical career, the emotional challenges of living with a chronic illness and the fear of unpredictability, advances in treatment options for NMO and the hope they bring to patients, and the power of resilience and determination in overcoming health challenges.DISCLAIMERThe information in this podcast is for informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions you may have regarding a medical condition or treatment.Links and resources:Sign up for the 10 Weeks to Disrupt MS ProgramFollow Dr. Summer on TikTok Visit Summer Banzhaf, DO at Fairfield Medical Center If you're interested in having Kathy speak at your event, learn more hereFind out more about the DMAT Fitness Training programYou can find Kathy Chester at: msdisrupted@gmail.comdisruptfitnessgym@gmail.com moveitorloseit109@gmail.com Connect with @msdisrupted on Instagram, Facebook, TikTok Here are some additional products that help Kathy beat the Heat and Migraines.  Take advantage of the coupon code.Koldtec - Cool Head WrapKOLD10To save $10 off every item in-store.2 items = $20 savings3 items = $30 savingshttps://www.koldtec.com/  Cold bean bag Releafpack15% discount use code Disrupt15https://www.releafpack.com  

Natalizumab (Tysabri, Tyruko) wird für aktive schubförmig remittierende MS eingesetzt als Infusion oder Spritze und wirkt sehr schnell. Den kompletten Beitrag zum Nachlesen findest Du auf meinem Blog: https://ms-perspektive.de/266-natalizumab Heute geht es um Natalizumab, das unter den Handelsnamen Tysabri und Tyruko bekannt ist. Die Immuntherapie wird bei aktiven, schweren Verläufen von schubförmiger MS eingesetzt. Natalizumab ist ein migrationshemmendes Medikament, das die Einwanderung von T- und B-Zellen in das zentrale Nervensystem verhindert. Bitte denke daran, dass ich hier nur einen Überblick geben kann. Dein Neurologe und deine MS-Schwester sollten dich bei der Wahl der richtigen Therapie ausführlich beraten. Denn sie kennen deinen allgemeinen Gesundheitszustand und du solltest auch über deine Ziele, Wünsche, Ängste und Vorlieben sprechen, damit diese berücksichtigt werden können. Inhaltsverzeichnis Allgemeine Informationen Wie wird Natalizumab (Tysabri, Tyruko) bei den Immuntherapien eingestuft? Wofür ist Natalizumab (Tysabri, Tyruko) zugelassen? Wie sieht die Situation für spezielle Patientengruppen aus? Wer sollte Natalizumab meiden? Wie wirkt Natalizumab? Wie wird es eingenommen? Wie wirksam ist Natalizumab (Tysabri, Tyruko)? Risiken und Nebenwirkungen von Natalizumab (Tysabri, Tyruko) Impfungen Quellen Schlussbemerkung Quellen Für die Erstellung der Inhalte habe ich die folgenden Quellen verwendet: Vorlesung zu Natalizumab von Prof. Dr. Thomas Berger im Rahmen des Masterstudiengangs Multiple Sklerose Management Qualitätshandbuch der deutschen KKNMS zu Natalizumab (Tysabri, Tyruko) MS-Selfie Infokarten von Prof. Dr. Gavin Giovannoni Deutsches Multiple Sklerose- und Kinderwunsch-Register (DMSKW) Informationen aus dem deutschen Interview mit Prof. Dr. Barbara Kornek über pädiatrische MS Deutsche DECIMS-Informationen zu Natalizumab --- Vielleicht möchtest du auch einen Blick auf die Beiträge zu den anderen Immuntherapien werfen: #256: Dimethylfumarat (Tecfidera) und Diroximelfumarat (Vumerity) #258: Glatirameracetat (Copaxone, Brabio) #261: Interferon-beta (Avonex, Betaferon, Extavia, Plegridy, Rebif) #264: Teriflunomid (Aubagio) Bis bald und mach das Beste aus Deinem Leben, Nele Mehr Informationen und positive Gedanken erhältst Du in meinem kostenlosen Newsletter. Hier findest Du eine Übersicht zu allen bisherigen Podcastfolgen.

Discover the intricate world of pharmacovigilance as Colleen Walsh, the Vice President of Global Patient Safety Operations at Alnylam, unveils her personal journey through the ever-evolving landscape of patient safety. In this enthralling episode of Innovation and the Future of Pharmacovigilance, I sit down with Colleen to unravel the complexities she's encountered, from the pivotal Tysabri incident at BioGen to leading R&D compliance at Alexion. Her story is a testament to the resilience required in the face of regulatory upheavals and the innovative spirit needed to navigate from clinical trials to post-market safety.In a field where the stakes are as high as the patients' lives, Colleen sheds light on the arduous task of merging companies within the rare disease sector, specifically the AstraZeneca acquisition of Alexion. Through her insights, we gain an understanding of the delicate balance between patient support programs and the scrutiny of global pharmacovigilance regulations. Colleen's expertise reveals the pressing need to bridge the gap between regulatory intent and its real-world application, ensuring that patient safety remains paramount while fostering a culture of innovation.Our discussion veers into the future of pharmacovigilance technology, examining how AI could revolutionize the industry yet poses unique challenges for both behemoths and fledgling companies in the pharmaceutical world. Colleen proposes an intriguing shift in perspective, advocating for pharmacovigilance to transition from a cost burden to a revenue generator by incorporating safety measures early in drug development. Join us on this episode as we probe into a future where pharmacovigilance not only safeguards patients but also drives value and progress in the realm of medicine.

In this episode of the new fortnightly series, the MS Boost, we discuss a new subcutaneous delivery mode for Tysabri, with MS nurse Louise Rath and the things you need to consider when making a switch, including the practical considerations, efficacy, logistics to costs and potential side effects.Check out a copy of the transcript here.With thanks to Louise Rath, MS NurseLouise Rath is the MS neuroimmunology nurse consultant at Alfred Health in Melbourne, Victoria. She has over 20 years' experience in public neurology services including outpatient appointments. Louise is the nurse clinical lead at the Alfred Multiple Sclerosis & Neuroimmunology Clinic focusing on patient experience, promoting engagement in health care and developing health literacy documents for the service with consumers.For more information about medications, call MS Plus Connect to speak with an MS Nurse Advisor.Reach out for support:MS Plus Connect 1800 042 138 or email connect@msplus.org.auGet in touch to share your comments and suggestions about this episode, or for future guests and episode topics by emailing education@ms.org.au 

Welcome to Living Well with MS. In this episode, we are sharing the highlights from one of our ‘Ask Aaron' webinars, where neurologist, Dr Aaron Boster, answers questions about MS from the community. In this episode, Dr Boster covers a range of topics, including heat intolerance, when to start a DMT and his tips for self-managing MS. You can watch the original webinar here. Keep reading for the key episode takeaways.   Topics and Timestamps: 02:13 Considerations for changing to a less stressful job and stronger DMTs. 05:09 Talking to clinicians about stress. 06:25 Hyperbaric oxygen therapy. 08:11 Stem cell transplants for PPMS. 10:35 Tysabri during pregnancy and breastfeeding. 12:23 MS and Stroke. 13:52 MRI showing brain cysts. 16:57 Betaferon and slow progression. 19:45 Changing from Tysabri to Ocrevus. 21:41 Vertigo. 23:05 Ampyra for walking, spasticity, and nerve pain. 25:50 Types of inflammation. 28:05 Anesthetic or epidural and MS. 30:15 B-cell depletion therapy and allergies. 31:17 Tips for self-managing MS. 37:42 Heat intolerance. 40:30 When to start on a DMT. 41:22 Ocrevus and low lymphocyte levels. 43:40 Diet and MS. 48:50 Nausea as an MS symptom. 51:30 CBD for MS. 52:45 Bursitis and MS. 53:36 Choosing a DMT and considering side effects. 55:16 Invisible illness in an ableist world. Selected Key Takeaways: Exercise as part of your daily lifestyle  34:42 “Exercising as part of a lifestyle means that if you do it, you're not rewarded. There's no reward for doing something as part of your lifestyle and if you don't do it, there's no punishment - you're not sent to the naughty corner. So, for example, I have a lifestyle of brushing my teeth. I don't tweet about it. I don't make YouTube videos about it. I don't even talk about it when I get to work. It's just something I do every morning and if I happen to forget to brush my teeth before I head off to the office, I'll run upstairs and do it. This is part of my lifestyle. So, I need people impacted by MS to exercise as part of their lifestyle.” Plan your day to minimise symptoms like heat intolerance 39:43 “We can conserve energy during those times when it's really hot out. Whereas I would normally encourage a patient to park at the back of the parking lot to get their steps in. If it's the middle of the day, [walking that far is] going to sap all your energy so that when you get to the grocery store you can't shop, that doesn't really work very well, does it? And so that's an example where we would have someone drop us off at the threshold of the grocery store so that you can be successful in your shopping.” Be brave in using mobility aids and seeking accommodations. 57:27 “I tell people who are embarrassed by their cane, ‘Don't you dare be embarrassed by your cane, a cane is a sign of intelligence.' A person with a cane would like to not fall. So, when a little boy is walking with [his] mum, and says, ‘Mummy, why is she using a cane?' That's an opportunity for the mother to say, ‘Well, she doesn't want to fall, she has a problem with her leg and the cane helps her.' It normalises it. So, one of the things that we need to do is to be brave. I'll remind you of the definition of bravery, ‘doing something despite being scared'. The second thing is, I want you to be very selfish. You need to be selfish; you live your life once. You're not living your life so some stranger, you don't know, thinks nice polite things about you.” Want to learn more about living a full and happy life with multiple sclerosis? Sign up to our newsletter to hear our latest tips. More info and links: Watch the original webinar here. Dr Boster was on three previous Living Well with MS episodes: S1E11: Making the Right Medication Choices   S2E17: Lifestyle Choices and Their Impact on MS  S3E43: Let's Talk About Sex (and MS) Check out Dr Boster's popular YouTube channel covering all aspects of MS. New to Overcoming MS? Visit our introductory page  Connect with others following Overcoming MS on the Live Well Hub Visit the Overcoming MS website Follow us on social media: Facebook Instagram YouTube Pinterest Don't miss out:  Subscribe to this podcast and never miss an episode. Listen to our archive of Living Well with MS episodes here. If you like Living Well with MS, please leave a 5-star review. Feel free to share your comments and suggestions for future guests and episode topics by emailing podcast@overcomingms.org. Make sure you sign up to our newsletter to hear our latest tips and news about living a full and happy life with MS. Support us: If you enjoy this podcast and want to support the ongoing work of Overcoming MS, we would really appreciate it if you could leave a donation here. Every donation, however small, helps us to share the podcast with more people on how to live well with MS.

Summary: In this week's New FDA Approval's podcast episode, Dr. Emma Hitt Nichols discusses the latest FDA approvals from August 21, 2023 – August  25, 2023.  Please check back every Monday morning so that you can stay up to date. See more details summaries and links to prescribing information at nascentmc.com/podcast Here are the highlights:  FDA Approves Tyruko as First Biosimilar to TysabriThe FDA approved Tyruko as the first biosimilar to Tysabri for treating relapsing forms of MS in adults. It has similar risks and side effects as Tysabri and is also approved for treating certain Crohn's Disease patients. The product is available from Sandoz Inc. Source Abrysvo RSV Maternal Immunization ApprovedThe FDA approved Abrysvo, a vaccine for preventing respiratory disease caused by RSV in infants through maternal immunization. The approval is based on Phase 3 MATISSE trial results. Abrysvo was also approved for older adults earlier this year. Source sBLA Filed for Rybrevant in Advanced NSCLCAn sBLA was filed for expanded approval of Rybrevant, combined with certain drugs, for treating advanced non–small cell lung cancer with EGFR exon 20 insertion mutations. The approval was granted to Janssen Pharmaceuticals. Source Priority Review of Xtandi in Early PCaXtandi received Priority Review by the FDA for an expanded use in early-stage prostate cancer. The sNDA is based on a Phase 3 EMBARK trial, where Xtandi showed significant benefits. The product is manufactured by Pfizer, Inc.  Intro and outro music Garden Of Love by Pk jazz Collective    

Experiencing difficulty walking is one of the most common mobility challenges faced by people living with MS. The good news is that there are things you can do -- both with a physical therapist and by yourself, at home -- that can make a real difference. Joining me to discuss improving your gait, avoiding falls, and what experts are learning from the latest research in this area is the Director of Research for the Department of Health Care Sciences at Wayne State University School of Medicine, Dr. Nora Fritz. We're also sharing the results of a study that looked at whether disease-modifying therapies had an impact on the number of hospitalizations or visits to the doctor someone with MS might experience over a 22-year period. We'll tell you about a study that measured the outcome for people with relapsing-remitting MS who were treated with autologous hematopoietic stem cell transplantation (aHSCT) compared with the outcome for people with relapsing-remitting MS who were treated with Gilenya, Tysabri, or Ocrevus. We'll share the results from a study that analyzed 56 other studies to determine the prevalence of sexual dysfunction among women living with MS. We'll tell you about a nationwide study that's about to get underway that will try to answer the question, 'Should people with MS over the age of 65 discontinue their disease-modifying therapy?' And we'll remind you about how you can join us in Napa Valley this Saturday, July 29th, for Crush MS. We have a lot to talk about! Are you ready for RealTalk MS??! This Week: Improving your balance and gait  :22 A research team analyzed the risk of hospitalization over a 22-year period for people with MS who were on a disease-modifying therapy and compared those results to people with MS who weren't on a DMT  1:21 Researchers compared patient outcomes associated with autologous hematopoietic stem cell transplantation (aHSCT) and compared them with outcomes associated with Gilenya, Tysabri, and Ocrevus  4:40 A research team in Iran analyzed results from 56 separate studies about sexual dysfunction in women with MS   8:29 Should someone over the age of 65 discontinue their disease-modifying therapy?   11:40 Dr. Nora Fritz discusses gait, balance, fall prevention and more   15:20 Share this episode  33:49 I'll be at Crush MS! Will I see you there?  34:09 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/308 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.com Phone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com STUDY: Disease-Modifying Drugs for Multiple Sclerosis and Subsequent Health Service Use https://pubmed.ncbi.nlm.nih.gov/34949130 Tremlett's MS Research Explained: Disease-Modifying Drugs for Multiple Sclerosis and Subsequent Health Service Use https://tremlettsmsresearchexplained.wordpress.com/category/ms-disease-modifying-drug-research STUDY: Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis https://pubmed.ncbi.nlm.nih.gov/37437240 STUDY: Prevalence and Risk of Developing Sexual Dysfunction in Women with Multiple Sclerosis (MS): A Systematic Review and Meta-Analysis https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-023-02501-1 RealTalk MS Episode 255: Aging With MS with Dr. John Corboy https://realtalkms.com/255 Crush MS https://crushms.org If you're living with MS, email info@crushms.org for special deep discount code Crush MS 10% Discount Code for everyone is Realtalkmsdiscount (case sensitive) Join the RealTalk MS Facebook Group https://facebook.com/groups/realtalkms Download the RealTalk MS App for iOS Devices https://itunes.apple.com/us/app/realtalk-ms/id1436917200 Download the RealTalk MS App for Android Deviceshttps://play.google.com/store/apps/details?id=tv.wizzard.android.realtalk Give RealTalk MS a rating and review http://www.realtalkms.com/review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 308 Guest: Dr. Nora Fritz Privacy Policy

Welcome to this week's episode of the Multiple Sclerosis Weekly Update, where we cover the most recent and impactful news related to MS. This week, we delve into a groundbreaking study that reveals a genetic variant influencing the severity and progression of MS in certain patients. We also unpack a legal dispute between Biogen and Novartis over the biosimilar of Tysabri and explore what this means for branded biologic-drug makers. Additionally, we discuss the surprising impact of myelin on axons in MS, compare the efficacy of rituximab and ocrelizumab, and reflect on Christina Applegate's journey with MS. Stay tuned for these stories and more in this week's episode.Here are the like to the articles: https://www.healthline.com/health-news/ms-symptoms-progress-more-quickly-in-certain-people-researchers-think-they-know-whyhttps://news.bloomberglaw.com/health-law-and-business/details-emerge-in-biogens-failure-to-block-biosimliar-tysabrihttps://www.news-medical.net/news/20230630/Myelin-can-be-harmful-to-axons-in-multiple-sclerosis.aspxhttps://www.physiciansweekly.com/comparing-the-efficacy-of-rituximab-and-ocrelizumab-for-relapsing-remitting-multiple-sclerosis/https://www.sportskeeda.com/health-and-fitness/news-david-faustino-speaks-christina-applegate-s-struggle-multiple-sclerosis-diagnosisThe Just MS (Multiple Sclerosis) Show, w host Justin Loizos, is a podcast that connects, educates and tries to uplift others living with multiple sclerosis. It provides real-life stories, interviews, and information about DMTs (disease modification therapies) and updates on research developments.www.justmultiplesclerosis.com

Dr. Terry Wahls discusses how to Reverse Multiple Sclerosis with Dr. Ben Weitz. [If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.]    Podcast Highlights 2:00  Dr. Wahls was diagnosed with Multiple Sclerosis 23 years ago, so she went to the best MS center in the country and saw their best physician and took the recommended latest drugs. Three years later she was going downhill and she was in a tilt, recline wheelchair despite taking the newest, disease modifying drugs, including Tysabri and Novantrone.  For her, these drugs did not help. She continued to worsen, as did the electrical face pains that she had.  She decided to dive deep into the research on her condition and she concluded that the mitochondria are the drivers of disability and she created a supplement cocktail for her mitochondria.  She changed her diet from vegan to paleo to provide protein and additional nutrients. She also discovered a study using electrical stimulation of muscles and added that to her physical therapy.  She then discovered the Institute of Functional Medicine and took their course on neuroprotection and developed a longer list of supplements.  Her condition was improving but she was not where she wanted to be. She then had an aha moment and decided to redesign her paleo diet to be able to get all of these nutrients in the supplements from her food. She did more research and then figured out the Wahls Paleo diet by December. At that point, she was so weak that she could only sit up for about 10 minutes in a regular chair before she had to be either in bed or a zero gravity chair and she could only take a few steps with walking sticks.  Her electrical face pain was much worse and she was beginning to have trouble with brain fog.  She started eating this way on December 26th. By the end of January, her pain is less, her brain fog is less, and her fatigue is also less. By the end of February, her physical therapist noticed that she was getting stronger, so he advanced her exercise. By the end of March, she was walking with walking sticks. And by the end of April, she wanted to try riding her bike and she had an emergency family meeting with her wife Jackie and her two children.  Her 13 year old daughter and her 16 year old son jogged along side on either side of her bike and she rides around the block on her bike and they are all crying.  And then every day she rides her bike more and more.  And in October, Jackie signs her up for the Courage Ride, 18.5 miles, which she completed.  This fundamentally changed how Dr. Wahls thinks about disease and health and it changes the way she practices medicine and it will change the focus of her clinical research.  She has now conducted seven clinical trials and is now starting her eighth clinical trial on multiple sclerosis. She's published over 70 peer reviewed posters, abstracts, scientific papers and nearly 30 of them on multiple sclerosis. And she has really made it her mission to let people know there is so much that we can do that can change the course of this disease. 6:50  Dr. Wahls was able to regain her health using a Functional Medicine approach focused on diet, lifestyle, and physical therapy.  Dr. Wahls noted that she is an academic doctor who believes in the best and newest drugs, technology, and devices. And she treated her disease very aggressively because she did not want to become a burden, but she continued to go downhill. When she read the package insert in the drugs she was taking, it said that she had a 2% risk of getting leukemia each time she took the drug.  She took Tysabri and it did not help, but her program of diet, targeted supplements, and electrical stimulation of muscles enabled her to achieve a remarkable level of function.  With the guidance of her neurologist, she was weaned off the drugs and has been off ...

If you've listened to this podcast before, you already know that we avoid hype, and we stick to talking about evidence-based science. So, let me say right up front -- today, the cause of multiple sclerosis is unknown. However, a research team has identified a bacterial toxin that may prove to be the cause of MS onset as well as MS relapses. Joining me for an exclusive conversation about this discovery is Dr. Timothy Vartanian, who leads the team that made the discovery, and Dr. Richard Rudick, whose career has focused on experimental therapeutics for MS, playing a key role in the development of both Avonex and Tysabri. We're also talking about a stem cell therapy called MSC-NP that, in a Phase 1 clinical trial, delivered positive outcomes among people living with progressive MS. We'll tell you about a study that demonstrated why EDSS alone does not accurately define an individual's MS journey. We're sharing news from the International Progressive MS Alliance about a new research pipeline that will focus on improving well-being for people living with progressive MS. And we'll tell you where you can catch a replay of the International Progressive MS Alliance's latest webcast, Developing Treatments to End MS Progression. We have a lot to talk about! Are you ready for RealTalk MS??! This Week: Is this the cause of MS?  :22 STUDY: MSC:NP, a stem cell therapy for MS, delivers a positive outcome among people living with progressive MS  1:33 STUDY: Does EDSS tell the whole story of your MS status?   5:03 The International Progressive MS Alliance funds a research pipeline focused on improving well-being among people living with progressive MS  8:42 Webcast Replay: Developing Treatments to End MS Progression   10:24 Dr. Richard Rudick and Dr. Timothy Vartanian discuss a new discovery that may lead scientists to the cause of MS   11:36 Share this episode  29:25 Have you downloaded the free RealTalk MS app?  29:46 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/292 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.com Phone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com STUDY: Epsilon Toxin-Producing Clostridium Perfringens Colonize the MS Gut and Epsilon Toxin Overcomes Immune Privilege https://www.jci.org/articles/view/163239 STUDY: Mesenchymal Stem Cell-Derived Neural Progenitors Attenuate Proinflammatory Microglial Activation Via Paracine Mechanisms https://futuremedicine.com/doi/10.2217/rme-2023-0005 STUDY: Cognitive Impairment, Fatigue and Depression in Multiple Sclerosis: Is There a Difference Between Benign and Non-Benign MS? https://msard-journal.com/article/S2211-0348(23)00134-7/fulltext#%20 International Progressive MS Alliance: Well-Being in Multiple Sclerosis Research Funding Opportunity https://progressivemsalliance.org/2023/03/15/well-being-in-multiple-sclerosis-research-funding-opportunity Prioritizing Progressive MS Rehabilitation Research: A Call from the International Progressive MS Alliance https://journals.sagepub.com/doi/pdf/10.1177/1352458521999970 Webcast Replay: Developing Treatments to End MS Progression https://www.facebook.com/watch/live/?ref=watch permalink&v=748824966910470 Join the RealTalk MS Facebook Group https://facebook.com/groups/realtalkms Download the RealTalk MS App for iOS Devices https://itunes.apple.com/us/app/realtalk-ms/id1436917200 Download the RealTalk MS App for Android Deviceshttps://play.google.com/store/apps/details?id=tv.wizzard.android.realtalk Give RealTalk MS a rating and review http://www.realtalkms.com/review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 292 Guests: Dr. Richard Rudick and Dr. Timothy Vartanian Tags: MS, MultipleSclerosis, MSResearch, MSSociety, RealTalkMS Privacy Policy

Welcome to Living Well with MS. In this episode, Geoff meets with Kathy Chester, a certified fitness trainer and podcaster with MS.   Keep reading for the key episode takeaways and Kathy's bio.  Make sure you sign up to our newsletter to hear our latest tips and news about living a full and happy life with MS. And if you're new to Overcoming MS, visit our introductory page to find out more about how we support people with MS.  Bio:  Kathy Chester hosts the Move it or Lose it Podcast and leads Women Who Disrupt MS, a support group facilitated through the Multiple Sclerosis Foundation (MSF). She is the owner and lead trainer of Disrupt Fitness Gym.  Fitness has always played a big role in her life. She became an aerobics and boot camp coach and went on to manage various studios. In 2015, she established Disrupt Fitness Gym: a program combining circuit and interval training to create the most efficient workout.  Kathy was diagnosed with Multiple Sclerosis more than 20 years ago. Her MS symptoms began with numb hands and feet, migraines, and cognitive issues. The DMT's and MS treatments she has tried include Avonex, steroids, chemotherapy, Tysabri, and now, Ocrevus. Taking these medications further confirmed her belief that movement and exercise is crucial for optimal health, strength, and mobility.  Her expertise has allowed her to train people with MS all over the world. She developed a new program called DMAT (Disrupt Move and Transform). DMAT targets joints and muscles to slow down advancement of the disease. The program is based on a one-on-one or group session. Both standing and seated moves are demonstrated and trained in real-time. The results are increased strength and confidence in everyday movements which leads to more independence, and therefore, a better quality of life.  Selected Key Takeaways  Understanding exercise to improve MS symptoms  As the MS changed, and as I grew in my knowledge and more certifications, then I was able to understand what moves needed to be done to strengthen our bodies, our legs, the foot drop, keeping the MS hug away, and things like that. So I started working with the MS and the autoimmune world.  The benefits of live exercise classes – giving feedback I also do it [exercise classes] via Zoom, where there could be seven to 10 people, and I'm showing seated moves and standing moves. I'm able to watch and say 'Hold on. Stop that. Let's do this instead.' So I can watch [and] ask, 'Is it cool enough where you are? Do you have water?' And I think that's a personal touch that I'm able to give.  Producing a podcast   I wanted to do a podcast for a long time. The gym just took so much of me. I listened to several different podcasts for years and tried to get my [own] idea of what I wanted it to be. I decided I wanted to have guests on with autoimmune diseases, a lot of them have MS. And then to get something that is inspirational, something that they do, and then have a doctor come on and really talk about the issue.  Related Links:  Try an Overcoming MS exercise video  Find out more about Kathy's Disrupt Move and Transform exercise program   Listen to Kathy's podcast Move It or Lose It   Don't miss out:  Subscribe to this podcast and never miss an episode. You can catch any episode of Living Well with MS here or on your favourite podcast listening app. If you like Living Well with MS, please leave a 5-star review on Apple Podcasts or wherever you tune into the show. Feel free to share your comments and suggestions for future guests and episode topics by emailing podcast@overcomingms.org.  Make sure you sign up to our newsletter to hear our latest tips and news about living a full and happy life with MS.  If you enjoy this podcast and want to support the ongoing work of Overcoming MS, you can leave a donation here. 

Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, reads a news article on how stem cell transplant is superior to Gilenya and Tysabri at preventing relapses and easing disability in RRMS patients. 
He also reads another report on how early use of DMTs may lead to lower levels of disability but does not appear to slow disability progression over time. =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/

Biogen has agreed to pay $900 million to resolve allegations that it violated federal law by paying kickbacks to doctors to persuade them to prescribe its multiple sclerosis drugs, federal prosecutors said. The agreement settled a whistleblower lawsuit brought by former Biogen employee Michael Bawduniak, according to a statement from the office of U.S. attorney for Massachusetts, Rachael Rollins. Under the terms of the settlement, Biogen will pay more than $843 million to the federal government and more than $56 million to 15 states for overbilling Medicare and Medicaid insurance programs. Bawduniak will receive a portion of the federal recovery. The Cambridge, Massachusetts-based pharmaceutical company in a statement said it settled so it can focus on “our patients and strategic priorities” and said the settlement does not include an admission of liability. “Biogen believes its intent and conduct was at all times lawful and appropriate and Biogen denies all allegations raised in this case,” the company's statement said. The lawsuit alleged that from January 2009 through March 2014, Biogen paid physicians speaking fees, consulting fees and bought them meals that were actually kickbacks, to get them to prescribe Avonex, Tysabri and Tecfidera in violation of the Anti-Kickback Statute. “We thank Mr. Bawduniak for uncovering this behavior and bringing it to light,” Rollins said. “This matter is an important example of the vital role that whistleblowers and their attorneys can play in protecting our nation's public health care programs.” This article was provided by The Associated Press.

Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, discusses how a newsletter's first issue is providing information on ways to manage pseudobulbar affect, one of the most underrecognized MS symptoms. He also reads “MS News That Caught My Eye Last Week: COVID-19 Vaccines, Robot Training, Bladder Treatment, Tysabri”, a column by Ed Tobias. =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/

Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, reads a news article on how Tysabri outperformed other MS treatments at lessening symptoms and improving work productivity. He also reads “Sometimes Pushing Boundaries With My MS Management Pays Off” by Beth Ullah, from her column “Through the Looking Glass.” =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/

Host: Barry A. Singer, MD Patients living with MS can experience hidden or invisible symptoms that may not be apparent to others but can affect how they feel and function. In this podcast, Dr. Barry Singer, the Director at the Multiple Sclerosis Center for Innovations in Care, and Rosario, a patient who has been living with MS for 10 years, discuss their clinical and personal experiences with MS, and the impact that MS can have on a patient's QoL. In the 2-year AFFIRM pivotal trial: Relapsing MS patients received 300 mg TYSABRI every 28 days (n=627) or placebo (n=315). Patients with PPMS, SPMS, and PRMS were excluded.2,3 83% of patients taking TYSABRI had no sustained disability progression for 12 weeks vs 71% with placebo (primary endpoint: 17% vs 29%; p

Host: Barry A. Singer, MD Patients living with MS can experience hidden or invisible symptoms that may not be apparent to others but can affect how they feel and function. In this podcast, Dr. Barry Singer, the Director at the Multiple Sclerosis Center for Innovations in Care, and Rosario, a patient who has been living with MS for 10 years, discuss their clinical and personal experiences with MS, and the impact that MS can have on a patient's QoL. In the 2-year AFFIRM pivotal trial: Relapsing MS patients received 300 mg TYSABRI every 28 days (n=627) or placebo (n=315). Patients with PPMS, SPMS, and PRMS were excluded.2,3 83% of patients taking TYSABRI had no sustained disability progression for 12 weeks vs 71% with placebo (primary endpoint: 17% vs 29%; p

Jenna Green worked for 15 yrs in corporate marketing, when she realized that she had to leave for the sake of her mental health! So she began working freelance - but the hustle culture, combined with chronic pain she experienced following a car accident, led her to a diagnosis of Multiple Sclerosis in 2016.On what should have been her first Tysabri infusion, she learned that her insurance wouldn't cover the treatment. This was Jenna's first experience of Step Therapy or Fail First practices - where, in order to control costs, insurance companies restrict coverage of expensive therapies unless patients have already failed treatment with a lower-cost alternative. And we all know that a failed treatment for MS means more relapses, leading to more irreparable damage, increased disability, and worse outcomes! Jenna is now a patient advocate, content creator, consultant, and public speaker. She has used her experience in marketing to help bring awareness, support, education, and community to those who live with invisible illnesses, chronic pain, and fatigue, primarily on Instagram @thejennagreen. AND she's devoted to helping to change public policy via her volunteer work with the MS Society. GO JENNA!Topics covered in this episode include:Jenna's life before her MS diagnosis, and her experience of Step Therapy or Fail First policiesHer belief that privilege equates to responsibilityThe alternative therapies that Jenna uses alongside conventional medicineHow Jenna became an MS advocate, and how this work makes her feelInformation about Jenna's exciting patient resource about Public Speaking For Patient Advocates (coming soon) Full show notes and resources at https://fumsnow.com/fums107/See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, reports on how Canadians with multiple sclerosis said cannabis was highly effective in treating sleep issues, pain, stress, fatigue, and muscle spasms. He also reads “MS News That Caught My Eye Last Week: Cannabis, Keto Diet, Tysabri, MS Unknowns”, from Ed Tobias' column, "The MS Wire." =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/

Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, explains how Tysabri given every six weeks was found as effective as the standard dosing at stopping nervous system damage in RRMS patients. He also reads “Recovering My Self-esteem After Adapting to MS-related Incontinence”, from Beth Ullah's, regular column "Through the Looking Glass." =================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/

Prof. Dr. Mathias Mäurer erklärt, wie die MS funktioniert, wie man sie am besten unter Kontrolle bekommt und wie Therapietreue schützt.   Hier geht es zum Blogbeitrag: https://ms-perspektive.de/therapietreue-bei-ms/ Willkommen zu Folge #132 vom MS-Perspektive-Podcast. Heute begrüße ich erneut Prof. Dr. Mathias Mäurer zu Gast im Interview. Wir sprechen über die Bedeutung der verlaufsmodifizierenden Therapie und wie wichtig es ist, seine Therapie auch langfristig so durchzuführen, wie es gedacht ist. Gerade im Social Media Bereich gibt es leider so einige Influencer, die zwar Patienten, aber eben keine Experten auf dem Gebiet der Behandlung von MS sind und Empfehlungen aussprechen, die wissenschaftlich betrachtet kompletter Unfug sind. Diese Folge soll helfen, wissenschaftlich basierte Fakten einfach verständlich zu erklären und Dir auf Deinem Weg mit der Erkrankung sinnvolle Tipps mitzugeben. Inhaltsverzeichnis Begrüßung Was passiert denn genau im Körper, wenn die MS aktiv ist? Wie viel von dieser Aktivität spürt man denn als Patient bewusst im schubförmigen Verlauf? Verkürzt die Kortison-Stoßtherapie vor allem die Dauer eines Schubes oder hat sie einen Einfluss auf die Langzeitprognose? Gibt es einen Unterschied was die Langzeitprognose angeht, bei der Blutwäsche? Können Sie bitte erklären, was man genau mit der verlaufsmodifizierenden Therapie erreichen will? Und wie sie wirkt? Was bedeutet denn genau Therapietreue? Welche medizinisch sinnvollen Gründe gibt es, eine verlaufsmodifizierende Therapie zu wechseln oder gar auszusetzen? Welche Therapieoptionen haben Frauen mit Kinderwunsch, die eine aktive MS haben? Was passiert denn, wenn ich eine aktive MS mit einer verlaufsmodifizierenden Therapie zum Stillstand gebracht habe und denke, jetzt ist alles gut und jetzt setze ich die Medikamente ab? Welche Risiken sind mit einem wiederholten Wechsel von Therapie und Therapieabbruch verbunden? Welcher Prognose sehen Menschen entgegen, die die MS mit, in Anführungsstrichen, nur einer gesunden Lebensweise eindämmen wollen? Wie sieht die Prognose von MS-Patienten aus, die eine wirksame Therapie nutzen, wo wirklich die Aktivität komplett unterdrückt wird, auch im subklinischen Bereich? Wie umkehrbar sind Spätfolgen, die sich im progredienten Verlauf der MS zeigen, nach aktuellem Stand der Forschung und Behandlungsoptionen? Sind Ihnen denn schon Patienten begegnet, die ihre frühere Entscheidung gegen verlaufsmodifizierende Medikamente bereut haben? Möchten Sie den Hörerinnen und Hörern noch was mit auf den Weg geben zum Schluss? Begrüßung Nele Handwerker: Hallo Herr Professor Mäurer, ich freue mich sehr, dass Sie da sind und heute den Hörerinnen und Hörern noch mal was zum Thema Therapietreue sagen. Muss ich nur Medikamente nehmen, wenn die MS aktiv ist? Danke, dass Sie sich so spontan Zeit genommen haben. Prof. Mathias Mäurer: Ja, sehr gerne, Frau Handwerker. Schön, dass ich mal wieder dabei sein darf. Und ich freue mich natürlich auf Ihre Fragen. Nele Handwerker: Wer Professor Mäurer nicht kennt, er hat einen Master of Health Business Administration, ist Chefarzt der Neurologie und neurologischen Frührehabilitation am Klinikum Würzburg Mitte, am Standort Juliusspital. Und ich hatte ihn schon mal zu Gast, In Folge 89 hat er sich ein kleines bisschen mehr vorgestellt. Hör gerne noch mal in die Folge rein. Aber kommen wir zu dem, worum es heute geht. Was passiert denn genau im Körper, wenn die MS aktiv ist? Prof. Mathias Mäurer: Ja, also letztlich ist der Schub ja an sich das, was die MS ausmacht. Den merkt der Patient und danach richtet sich natürlich so ein bisschen das, wie die MS bewertet wird. Aber im Endeffekt muss man natürlich sagen, was die MS wissenschaftlich ausmacht, ist die Attacke des Immunsystems auf das zentrale Nervensystem. Das kann nicht nur im Sinne von Schüben manchmal passieren, sondern wir haben generell eine entzündliche Aktivität, die wir teilweise nur im Kernspintomogramm sehen. Man kann ungefähr rechnen, dass auf einen klinischen Schub circa zehn Läsionen in der Kernspintomographie kommen. Das heißt, der Schub alleine ist jetzt kein unbedingt ausreichender Maßstab, um die Aktivitäten der MS zu bewerten, sondern meistens ist es die Kombination aus dem, was klinisch passiert, der Kernspintomographie und dem, wie sich der Patient fühlt. Da werden ja auch teilweise bei uns Screening Methoden gemacht wie die Gehstrecke, das Stäbchen stecken oder auch kognitive Tests, und Fatigue-Skalen, wo man insgesamt bewerten kann, wie aktiv die Erkrankung zum Zeitpunkt ist. Nele Handwerker: Hmm, okay. Genau dieses 1:10, das kannte ich auch. Das hatte mich damals auch ein bisschen schockiert, aber auch sofort davon überzeugt, dass ich besser was gegen die MS bei mir unternehmen sollte. Wie viel von dieser Aktivität spürt man denn als Patient bewusst im schubförmigen Verlauf? Nele Handwerker: Also Sie haben es jetzt schon im Prinzip gesagt und im verborgenen…. Prof. Mathias Mäurer: Ja, wobei ich, ich kann es gerne auch noch so ein bisschen spezifizieren. Es ist ja tatsächlich so, das zentrale Nervensystem ist groß. Gerade das Gehirn hat natürlich Regionen, wo es Stellen gibt, wo Sie Entzündungen haben können, ohne das jetzt direkt zu merken. Also Sie merken die Entzündung in der Regel meistens nur dann, wenn Sie einen Entzündungsherd in einer eloquenten Region haben. Unter eloquent verstehen wir Regionen, die wirklich klar einer Funktion zugeordnet sind. Also wenn Sie irgendwo in einer motorischen Bahn was haben, dann haben Sie eine Lähmung. Wenn Sie im Sehnerv was haben, sehen Sie nichts. Aber wenn das irgendwo im Parietallappen liegt oder irgendwo periventrikulär , dann müssen Sie nicht unbedingt von einer entzündlichen Aktivität was merken. Es gibt Theorien, dass man sagt, dass vielleicht die Fatigue sozusagen auch so eine Art, ja, Summenmarker für Entzündungsaktivität ist. Also wenn Patienten auch merken, sie fühlen sich irgendwie doch sehr leistungsgemindert, dass es unter Umständen auch ein Zeichen dafür sein kann, dass sich da irgendwas tut. Aber in der Regel können gerade Läsionen im Gehirn selber häufig stumm sein. Im Rückenmark merkt man sie eher, weil da viele wichtige Bahnen eng beieinander liegen. Aber im Gehirn selber ist es manchmal als Patient gar nicht wahrscheinlich, dass man merkt, was da passiert. Nele Handwerker: Passt genau zu dem, was ich erlebt habe, auch wenn mein einer Fall nicht statistisch relevant ist. Bevor ich mit einer Therapie begonnen habe, hatte ich mit der Fatigue total Probleme. Nachdem meine Therapie nach drei Monaten gegriffen hat, hat sich zum Glück alles zurückentwickelt. Da geht es auch so ein bisschen um die neurologische Reserve. Das Gehirn hat gewisse Kapazitäten zum Umbauen und wenn die aufgebraucht sind, rutscht man in den chronischen Verlauf. Prof. Mathias Mäurer: Genau, die Sache mit der neurologischen Reserve oder Brain Reserve, wie es auch genannt wird, in der Fachliteratur, das ist schon eine ganz, ganz wichtige Sache. Und das muss man sich eben auch vor Augen halten, dass man natürlich als junges Gehirn, und bei vielen MS-Patienten fängt die Erkrankung ja doch in sehr jungen Jahren an, eine extrem große Kompensationsreserve hat. Also man kann vieles was dann passiert, gerade in den jungen Jahren, einfach wegstecken. Und dadurch letztlich zwischen den Schüben überhaupt nichts merken. Man fühlt sich vielleicht bis auf die Fatigue relativ gesund. Es gibt aber sehr schöne Studien. Ich weiß nicht, ob ich die mal schildern darf. Das ist so funktionelle Kernspintomographie, wo man letztlich sehen kann, wie viel Hirn muss eigentlich jemand aktivieren, um eine bestimmte Aufgabe durchzuführen. Da gibt es sehr schöne Untersuchungen. Bei einem Gesunden, wenn der eine Bewegung macht, dass Finger so hin und her tappen, da wird im Prinzip nur der motorische Cortex und ein paar prämotorische Areale aktiviert. Wenn das gleiche ein MS-Patient macht und der muss überhaupt nicht irgendwie im Bereich der Handfunktion betroffen sein, das reicht, wenn es jemand war, der eine Sehnervenentzündung hatte und vielleicht ein paar entzündliche Flecken, dann sieht man, dass der für die selbe Motoraufgabe letztlich viel mehr Hirnsystem aktivieren muss. Das heißt, der nutzt schon viel mehr von seiner Reserve um das gleiche auszuführen. Ich vergleiche das immer mit so einem Motor, der letztlich viel, viel höher dreht als der Motor von einem Gesunden. Und genauso wie beim Auto, wenn Sie das lange machen, dann haben Sie irgendwann einen Motorschaden. Und das ist es, was bei der MS passieren kann. Wenn sie lange immer wieder ihre Kompensationsfähigkeit belasten, ist sie irgendwann aufgebraucht. Und in dem Moment merkt man die MS dauerhaft. Und das ist häufig, aber erst im mittleren Lebensalter der Fall. Sprich, derjenige, der die MS früh bekommt und seine Reserve aufbraucht, weil er halt sonst nichts machen möchte, der wird nach einer gewissen Zeit in Schwierigkeiten laufen. Jetzt ist mir auch ganz wichtig, ich möchte nicht mit Ketten rasseln, weil das immer ein bisschen doof ist, wenn man mit irgendwelchen Konsequenzen droht. Nicht jede MS ist gleich und das heißt nicht bei jedem, wenn er jetzt, sagen wir mal, therapeutisch komplett ablehnend ist, dass das gleich im Desaster landen muss. Aber es gibt halt, sagen wir mal, vielleicht so prozentual allenfalls 20 bis 30 %, die auch da Glück haben mit der Erkrankung. Bei der überwiegenden Mehrzahl läuft es halt doch so, wie ich es sage, ja, dass man eben unter Umständen in Probleme reinläuft, wenn man das System zu sehr stresst. Nele Handwerker: Und das ist dann schon arg, quasi Roulette spielen mit der eigenen Gesundheit. Jetzt kommen wir mal zur Kortison-Stoßtherapie. Ich habe oft genug von Leuten gehört, die denken, dass es ganz wichtig ist, super hilft, und auch die Langzeitprognose positiv beeinflusst. Verkürzt die Kortison-Stoßtherapie vor allem die Dauer eines Schubes oder hat sie einen Einfluss auf die Langzeitprognose? Prof. Mathias Mäurer: Es gibt keine verlässlichen Studien, die irgendwie zeigen, dass Kortison an der Langzeitprognose der Multiplen Sklerose was macht. Das hat sich nie in Studien wirklich beweisen lassen. Es ist noch nicht mal so, dass man jetzt unbedingt sagen kann, dass Kortison auch im Schub irgendwas macht. Es gibt sogar Arbeiten, also im Tiermodell, die zeigen, dass Kortison schädlich sein kann bei einer Opticus Novartis. Wir gehen davon aus, dass Kortison schon in der Lage ist, gerade hoch dosiert, bestimmte Entzündungszellen in den programmierten Zelltod zu schicken. Also dass die Entzündungszellen Selbstmord begehen, und dass dieser Selbstmord, relativ positiv ist für die Entwicklung des Schubes. Aber eben nur als Akutmaßnahme und sicherlich nicht als Langfrist-Maßnahme. Ich weiß, dass viele Patienten auf diese wiederholten Kortisonstöße schwören, gerade auch in späteren Krankheitsphasen. Das hat aber unter Umständen damit zu tun, dass Kortison auch ein bisschen euphorisierend wirkt, dass es anti-spastisch wirkt und dass es natürlich so einen doch kurzen Effekt hat, das man sich besser fühlt. Aber diese langfristigen Effekte, die manche auch propagieren, die sind wirklich nie bewiesen worden. Also man kann das Kortison, und das machen wir ja auch im akuten Schub, natürlich einsetzen und das ist auch eine wichtige therapeutische Maßnahme, aber für die Langzeitprognose der Erkrankung und für den Langzeitverlauf zählt eigentlich nur die immunmodulatorische Therapie und da zählt das Kortison gar nicht dazu. Weder als Hochdosis und schon gar nicht als orale Dauertherapie. Auch diese Meinung ist manchmal noch anzutreffen und da schlage ich immer die Hände über dem Kopf zusammen. Weil das, was wir bei der MS machen, das funktioniert ja auch nur bei diesen wirklich sehr, sehr hohen Dosen. Kortison niedrig dosiert, da nimmt man nur die Nebenwirkungen mit und hat eigentlich diesen Vorteil, dass man Entzündungszellen in den programmierten Zelltod schickt überhaupt nicht. Da braucht man Hochdosis-Konzepte dafür und nicht diese niedrig dosierten oralen Konzepte. Also ich würde ganz klar propagieren Kortison bitte aus der Liste der Langzeitprophylaxen komplett streichen. Das ist eine Schubtherapie. Nele Handwerker: Ja. So hatte ich es auch verstanden. Aber Ihre Erläuterungen dazu sind nochmal sehr wertvoll. Gibt es einen Unterschied was die Langzeitprognose angeht, bei der Blutwäsche? Nele Handwerker: Wenn man die vornimmt, ist da schon irgendwas klar? So lange wird die Blutwäsche ja noch nicht eingesetzt. Prof. Mathias Mäurer: Ja, also das ist gar nicht so einfach zu beantworten die Frage. Es gibt natürlich bestimmte MS-Pathologien, wo auch Antikörper eine Rolle spielen. Das kann man aber im Moment jetzt noch nicht unbedingt von außen festlegen. Deswegen ist es so, die Blutwäsche spielt dann eine Rolle, wenn die Kortisontherapie in einem Schub keine deutliche Verbesserung bringt. Das Schema ist ja so, dass man erst mal einen Kortisonstoß geben soll. Wenn das nicht zu einer Verbesserung führt, dann kann man so nach ein zwei Wochen entweder den Steroidschuss wiederholen oder alternativ die Blutwäsche einsetzen. Und wenn man da sehr gute Erfolge dann hat, dann ist es unter Umständen auch bei den nächsten Schüben sinnvoll man fängt gleich mit der Blutwäsche an, weil dann scheinbar die Antikörperpathologie im akuten Schub eine größere Rolle spielt als die T-Zell-Pathologie. Wahrscheinlich ist es bei jedem irgendwo eine Mischung sein. Aber vermutlich gibt es individuell Unterschiede, wie viel Anteil pathologische Antikörper im Schub haben, um eine Funktionsstörung hervorzurufen und wie viele Anteile die zelluläre Immunität hat. Das ist dann leider ein bisschen Versuch und Irrtum. Man kann nicht von außen vorhersagen, wer auf was besser anspricht. Deswegen ist es zumindest bei den ersten schweren Schüben immer Versuch und Irrtum. Aber da die Blutwäsche ein bisschen invasiver ist als die Kortisongabe, man braucht ja in der Regel einen sehr großvolumigen Katheter in der Jugularvene, das ist nicht so angenehm, wird man das nicht bei milder Schubsymptomatik machen. Das sind Maßnahmen, die für schwere Schübe mit Erblindung, mit schwerer motorischer Störung, mit einer schweren Gleichgewichtsstörung vorbehalten sind. Wenn es nur kribbelt, verzichtet man auf Blutwäsche. Das wissen vielleicht auch viele Zuhörer, so ein sensibler Schub, der kann manchmal hartnäckig sein und länger dauern, bis er wirklich komplett weggeht. Kortison ist k eine Garantie dafür, dass das Kribbeln weggeht. Da muss man manchmal ein bisschen Geduld haben. Denn wir müssen immer Nutzen und Risiko gegeneinander abwägen, auch in der Schubtherapie. Deswegen die Blutwäsche hat eine wichtige Bedeutung, vor allen Dingen eben bei schweren Schüben, wenn das mit dem Kortison nicht so klappt, wie man es sich wünscht. Nele Handwerker: Ja, so war es bei mir auch. Ich hatte vor Therapiebeginn einen Sensibilitätsschub. Da wurde nichts gemacht, sondern einfach gesagt, okay, jetzt bitte die verlaufsmodifizierende Therapie beginnen, weil beim Abwägen von Nutzen und Risiko, entschwieden wurde auf Kortison zu verzichten. Und die Blutwäsche habe ich zum Glück bisher noch nicht benötigt. Meine Therapie wirkt. Prof. Mathias Mäurer: Ja, das ist tatsächlich eine Methode, die eher seltener angewandt wird auf die Gesamtzahl von Schüben. Wie gesagt, die meisten Schübe der MS sind ja so, dass man sie unter Kontrolle kriegt. Und häufig haben sie nicht so ein ganz extremes Ausmaß. Nele Handwerker: Ja, zum Glück. Jetzt haben Sie schon die verlaufsmodifizierende Therapie angesprochen. Können Sie bitte erklären, was man genau mit der verlaufsmodifizierenden Therapie erreichen will? Und wie sie wirkt? Prof. Mathias Mäurer: Na ja, alle verlaufsmodifizierenden Therapien, also die ganze Palette von, ich glaube, jetzt mehr als 17 Medikamenten, die wir haben, sind Medikamente, die versuchen das Immunsystem ein wenig zu unterdrücken. Also MS ist ja eine Erkrankung, wo kein Immundefekt vorliegt, im Gegenteil, MS-Patienten haben eher ein Immunsystem, was ein bisschen zu gut funktioniert. Und alle diese Medikamente versuchen dieses etwas zu gut funktionieren wegzunehmen, die Spitzen wegzunehmen, und dennoch die normale Immunfunktion zu erhalten. Das Prinzip ist letztlich bei allen das Gleiche, das Immunsystem auf irgendeine Art und Weise zu beruhigen. Und da gibt es verschiedene Strategien. Unterschiedliche Wirkstoffklassen haben unterschiedliche Ansätze. Grundsätzlich ist es so, dass man versucht, diese Überaktivität des Immunsystems langfristig runterzufahren. Und das ist genau das, was dabei hilft, dass es nicht zu Attacken auf das zentrale Nervensystem kommt und das auch die subklinische Krankheitsaktivität unterbunden wird, die man vielleicht als Patient gar nicht merkt. Letztlich geht es langfristig darum, Entzündungsaktivität, egal ob das jetzt Schübe sind oder neue MRT-Läsionen möglichst effizient zu unterdrücken. Nele Handwerker: Und damit auch die neurologische Reserve zu schonen, damit es dann bitte nie in den chronischen Verlauf übergeht. Prof. Mathias Mäurer: Genau, Sie können jetzt nämlich eigentlich fragen, ja, was bringt mir das, wenn ich jetzt selten Schübe habe und vielleicht auch gar nicht so viele MRT-Läsionen, ist das dann wirklich sinnvoll, so was auch zu machen? Das Problem ist, dass wir mittlerweile ganz gut wissen, dass diese Entzündungseinwirkungen auf das Gehirn auch am Hirngewebe selber wahrscheinlich irgendeine Art von, ich sage mal, Sollwertverstellung macht. Also irgendwie wissen wir, dass wohl die ortständigen Entzündungszellen im Gehirn anfangen überzureagieren. Und dass es dann sogar unabhängig von Schüben, die ja von außen, also im peripheren Immunsystem getriggert werden, auch im Hirn selber eben gewisse Veränderungen des ortständigen Immunsystems gibt. Wir haben vor allen Mikrogliazellen im Verdacht, dass sind so ortständige antigenpräsentierende Zellen, Unterstützungszellen für Entzündungszellen, dass die anfangen so ein bisschen durchzudrehen. Und die drehen umso mehr durch, je mehr man letztlich auch Entzündungsreaktionen hat einwirken lassen. Man hat im Moment schon die Ahnung, dass das wahrscheinlich bereits mit Beginn der Erkrankung losgeht, diese Gefahr, dass man so eine, ja, wir nennen das Entzündung im Hirnkompartement selber bekommt. Deswegen bin ich ein Freund davon, auch wenn das sich am Anfang vielleicht harmlos anlässt, so eine MS, von Anfang an wirklich sehr, sehr konsequent zu therapieren, weil die Konsequenzen wahrscheinlich noch umfangreicher sind, als wir bisher gedacht hatten. Und der Nutzen, den man gerade früh erreichen kann, der scheint noch größer zu sein, als wir bisher gedacht haben. Ich bin wirklich dafür, von Anfang an Therapien zu empfehlen. Und dieses ‚Watch and Wait‘ ist nicht mein Ding, ja, weil ich einfach die MS doch als ernsthafte Bedrohung für die langfristige Gesundheit sehe. Nele Handwerker: Ich auch. Und diese Aufklärung, wie sie es gerade machen, ist mit ein Grund, warum ich diesen Podcast mache. Prof. Mathias Mäurer: Wie gesagt, am Anfang wird das alles gut weggesteckt. Am Anfang ist das kein Problem. Da tut man die paar Schübe, die paar Entzündungsläsionen mit seiner Hirnreserve relativ gut kompensieren, also ungeschehen machen. Aber man verbraucht natürlich einen Kredit. Und das halte ich für sehr gefährlich. Deswegen ist mein Ansatz, bei allem, sagen wir mal Verständnis, dass man natürlich als junger Mensch nicht unbedingt dauerhaft Medikamente nehmen will oder dass man auch Angst hat, sich da irgendwie zu belasten oder unnötige Nebenwirkungen einzukaufen, dass man eben nicht vergessen soll, dass dagegen durchaus eine Bedrohung von einer Erkrankung steht, die einem im Laufe des Lebens einfach Ärger machen kann. Und man ist ja nicht immer 20. Also ich kann es jetzt sagen, man möchte auch mit Mitte 50 noch ein gutes Leben haben. Und nicht unbedingt an irgendwelchen Symptomen leiden, auch wenn es nur Kleinigkeiten sind. Auch eine Blasenstörung kann einem das Leben vermiesen zu dem Zeitpunkt. Und wenn eine Chance hat, das zu unterdrücken, dann würde ich die nehmen und würde mich nicht auf irgendein Achtsamkeitsgeschwurbel einlassen, dass man auf die Therapie auch verzichten kann und dass man selber entscheiden kann. Natürlich kann man selber entscheiden, was man macht, aber bitte auf einer Wissensbasis entscheiden und nicht auf irgendeinem Blödsinn, der verbreitet wird. Oder was, was man sich vielleicht selber ausdenkt oder sich von irgendwelchen Influencern im Internet abgeguckt hat. Bitte mal die Fachliteratur lesen. Ich bin total liberal, wenn ich merke, der Patient hat sich sorgfältig informiert und trifft die Entscheidung wirklich auf einer informierten Basis. Da gehe ich mit. Weil letztlich jeder für sich selber entscheiden muss. Aber wo ich echt aggressiv werde ist, wenn man mir irgend so einen Scheiß erzählt, der überhaupt keinerlei Entsprechung hat in dem, was wir wissenschaftlich im Moment wissen. Irgendein Mist, der so mit Allgemeinplätzen und, ja, ich sag mal, Wellness-Blabla bestückt ist. Also da kann ich überhaupt nicht mit. Nele Handwerker: Ja, das habe ich ja auch schon zum Teil angesprochen. Es ist eine Sache, wenn man wissend, sehenden Auges da reinläuft und sagt, ich kann damit leben, dass ich irgendwann mal chronisch belastet sein könnte. Prof. Mathias Mäurer: Oder auch sagt, ich gehe das Risiko ein. Das ist in Ordnung. Aber nicht praktisch mit so einer kompletten Beschränktheit. Also dann erwarte ich schon, wenn man sagt, ich stehe für mich selber ein, dass ich mich dann auch anständig informiert habe. Und anständig informieren heißt eben auch nicht irgendeinem, sagen wir mal, Laien auf den Leim gehen, sondern sich wirklich bei denen informieren, die auch ein bisschen Ahnung haben von dem Thema. Nele Handwerker: Ja, übrigens, was Sie angesprochen haben, ist ja diese ‚Hit Hard and Early‘-Strategie. Für dich da draußen, falls du es noch nicht kennst. Dazu hatte ich eine Folge mit Professor Schwab aufgenommen. Er erklärt darin sehr schön, warum man zeitig mit einer hochwirksamen Therapie einsteigen sollte und das ganze Drumherum. Und ich hatte jetzt neulich erst von einem guten amerikanischen Podcast gehört, dass die eine Studie in Schweden durchgeführt wurde, wo Daten mit Dänemark verglichen wurden. Ähnliche Gesundheitssysteme und Rahmenbedingungen, und wer zeitig und stark einsteigt… Prof. Mathias Mäurer: Ja das ist eine sehr, sehr, sehr spannende Geschichte der skandinavischen Register, die sind ja sehr, sehr gut. Da wird jeder Patient auch sehr sorgfältig eingeschlossen, also die Datenqualität ist super. Und es ist tatsächlich so, dass die Schweden wesentlich aggressiver therapieren als der Rest von Europa. Die haben halt Rituximab für sich entdeckt, also so eine B-Zellen depletierende Therapie, die wird da auch staatlich unterstützt, dass man sie gibt. Und da ist ein sehr, sehr hoher Prozentsatz der schwedischen MS-Patienten, die Rituximab kriegen. Ich glaube, um die 34 %, wohingegen in Dänemark mit so einer Therapie nur in knapp 7 % der Fälle begonnen wird. Und wenn man die Dänen und die Schweden einfach so nebeneinander laufen lässt ge-machted, dann haben die Schweden ein wesentlich niedrigeres Progressionsrisiko als die Dänen. Und das ist echt eine gut gemachte Studie. Die finde ich auch von der Anzahl her gut. Es wurde eine hohe Anzahl an Patienten eingeschlossen. Bei anderen Studien gab es immer die Kritik, das sind viel zu wenig Patienten, die ihr da aus den Registern rauszieht, aber bei diesen beiden Registern, das sind schon so knapp 2000 Datensätze, die man miteinander vergleichen kann, das ist schon ein Wort. Und dementsprechend verhärtet sich die Theorie, dass eine konsequente Therapie gleich am Anfang wirklich Sinn macht. Was bedeutet denn genau Therapietreue? Prof. Mathias Mäurer: Ja, also sagen wir mal, man kann das wissenschaftlich als sogenannte Medikation Procession Rate ausdrücken. Praktisch bedeutet es, dass man einfach die eingenommene Medikation mit den Tagen abgleicht, wo sie hätte eingenommen werden sollen. Man sagt eine gute Therapietreue ist, wenn 80 % der Medikation genommen wurde. Mehr wäre wünschenswert, aber man weiß ja, wie das Leben so ist, dass man das nicht immer auf die Reihe kriegt ein Medikament regelmäßig zu nehmen. Und dementsprechend sind wir mit 80 % schon ganz zufrieden. Aber man weiß auch, wenn der Wert unter 80 % fällt, dann kriegt man nicht mehr die volle Wirkung des Medikamentes. Also Therapietreue ist schon ein ganz entscheidender Punkt, weil Medikamente, die nicht genommen werden können nicht wirken. Und natürlich ist es dann auch entscheidend, was habe ich für eine ‚Burden of Therapy‘, also eine Therapiebelastung habe. Die steht immer dagegen. Deswegen sind wir durchaus begeistert von Medikamenten, die nur relativ selten gegeben werden müssen. Wo man eventuell mit halbjährlichen Infusionen oder eben auch mit Tabletteneinnahmen zweimal im Jahr gute Ergebnisse erzielt. Denn da hat man meistens eine sehr hohe Adherenz. Ich bin mir manchmal nicht so sicher, ob Tysabri auch gerade deswegen so ein Knaller war als Medikament ist, weil es eben immer von Ärzten gegeben wurde. Schließlich hat man die Patienten somit immer voll unter Kontrolle. Und da war die Therapietreue natürlich wahnsinnig hoch. Wohingegen wir wissen, dass zum Beispiel Interferon, was ja auch unangenehm zu nehmen ist, manchmal nur so eine Medikation Possession Rate von um die 40 % hat. Und da können Sie natürlich die Wirkung vergessen. Also von daher Adhärenz, ist ganz wesentlich. Natürlich entdecke ich manchmal auch dieses Schema. Ich gehe immer davon aus, dass ein Patient sich bemüht, die Medikamenteneinnahme ganz gut zu machen. Dennoch frage ich auch immer nach, ob man es geschafft hat, das einzuhalten. Ich gehe gar nicht davon aus, dass das regelmäßig ist. Jemand, der mir sagt, ich habe es immer genommen, dem glaube ich sowieso nicht, weil das geht nicht. Geht mir auch selber so, ich versage schon bei Antibiotika, die regelmäßig einzunehmen, was ja wirklich wichtig ist und kurz. Von daher fragt man eher, wie viel haben Sie jetzt versäumt oder hat es ganz gut geklappt oder nicht? Und ja, das ist letztlich schon ein wesentlicher Punkt mit der Therapietreue, dass man verhindert, dass dann so Schemata aufkommen wie, ich nehme das nur, wenn es mir schlecht geht. Also wenn man so was entdeckt, dann muss man noch mal ernsthaft miteinander reden, dass das so nicht gedacht ist. Und man kann ja auch über alles reden. Wenn das Schema wirklich zu anstrengend ist für jemanden durchzusetzen, dann muss man schauen, was noch an Alternativen möglich ist. Es gibt ja durchaus die Möglichkeit zu einer individualisierten Therapie, eben weil wir so viele Präparate haben. Irgendwas wird man finden, was mit dem persönlichen Leben gut vereinbar ist. Aber dieses, ich mach das mal so zwischendurch, wenn es mir nicht so gut geht oder mal nach einem Schub, das geht am Ziel vorbei. Nele Handwerker: Ja, da bin ich doch froh, dass meine Eltern mir klare Linie beigebracht haben. Ich musste mein Medikament die ersten Jahre siebenmal die Woche spritzen, irgendwann wurde das Präparat angepasst und seitdem muss ich mir nur noch dreimal die Woche spritzen. Und ja, ich habe mir dann mal zum Geburtstag frei gegeben oder zu Weihnachten. Aber ansonsten, wenn es ging, nachgeholt. Prof. Mathias Mäurer: Da habe ich auch ganz hohen Respekt, wenn das jemand so durchzieht. Ich finde das schon bewundernswert und ich kann mir vorstellen, dass das schwierig ist. Deswegen, versuche ich meine Patienten immer zu ermuntern, dass sie klar sagen, was sie meinen zu schaffen und was eben nicht. Grundsätzlich ist das, wie wir eben besprochen haben, mit der Therapietreue eine ganz, ganz wesentliche Sache, um auch Therapieerfolge zu erzielen. Und ich finde, jeder Patient hat das Recht zu sagen, ja, das schaffe ich oder das schaffe ich nicht. Es macht ja keiner mir zuliebe. Davon sollte man sich lösen. Mir tut niemand einen Gefallen damit, wenn er seine Medikamente regelmäßig einnimmt. So erwachsen muss man sein, dass man sagt, das ist letztlich für mich. Ich bin nur dafür da, um zu helfen, wie man es möglichst optimal hinbekommt. Welche medizinisch sinnvollen Gründe gibt es, eine verlaufsmodifizierende Therapie zu wechseln oder gar auszusetzen? Nele Handwerker: Es gibt ja bestimmt welche, wo Sie sagen, das ist okay an der Stelle. Prof. Mathias Mäurer: Na ja, wir haben über den Convenience-Aspekt gesprochen. Da darf man natürlich wechseln. Man darf wechseln oder man soll sogar wechseln, wenn das Medikament nicht das macht, was es tun soll. Man darf natürlich auch wechseln, wenn irgendwie Nebenwirkungen nicht beherrschbar sind. Das sind alles Gründe. Und natürlich darf man auch das Absetzen mal ins Feld führen. Wir haben da auch von den Leitlinien schon eine klare Vorstellung, wo man sagen kann, hier kann ich auf ein Medikament verzichten. Also wenn tatsächlich jemand über Jahrzehnte mit einer Basistherapie komplett stabil war und auch nach den initialen Schüben nichts mehr gekommen ist, kann man selbstverständlich auch mit dem Patienten, wenn es dann schon ein höheres Lebensalter ist, über 45, besprechen, dass man es absetzt. Es gibt die Leitlinien die sagen, nach fünf Jahren mit einer moderat wirksamen Therapie kann man darüber sprechen. Ich habe viele gesehen, die dann doch wieder Schübe bekommen haben. Von daher, bin ich da etwas vorsichtiger, auch bei den moderat wirksamen und würde sagen, eigentlich sollte man vor dem 45. Lebensjahr die Diskussion nicht unbedingt beginnen. Aber wenn es in diese Altersklasse geht und die MS war lange stabil und es war jetzt auch keine allzu schwere Verlaufsform, dann kann man darüber reden. Ein bisschen anders ist es bei den hochaktiven Patienten, die von Anfang an eine sehr hohe Krankheitlast gehabt haben, die man nur mit sehr hochwirksamen Medikamenten still bekommt. Da wäre ich insgesamt sehr, sehr zurückhaltend überhaupt abzusetzen, weil das häufig in die Hose geht. Letztlich muss man sich ja auch vor Augen halten, wenn so eine MS stabil ist, die einen als chronische Erkrankung begleitet über zumindest das mittlere Lebensalter, dann hat man genau das erreicht, was man will. Und dann ist das Absetzen zwar ein verständlicher Wunsch, aber eigentlich hat man wahrscheinlich nur durch das Medikament diese Situation erreicht und dementsprechend sollte man es beibehalten. Also ich bin immer so ein bisschen zurückhaltend, aber klar, man kann auch Absetzen besprechen unter bestimmten Voraussetzungen. Nele Handwerker: Also ich kann dazu nur sagen, bei mir war die MS auch lange stabil und ich nutze quasi Medikamentenklasse 1, Basismedikation. In der Schwangerschaft habe ich anderthalb Jahre ausgesetzt und ich hatte nach der Geburt auch eine kleine sensitive Störung und habe meine Therapie dann wieder fortgesetzt. Nun habe ich noch nicht die 45 erreicht. Dreieinhalb Jahre habe ich noch bis dahin. Aber ich persönlich rechne im Moment auch damit, dass ich das bis an mein Lebensende nehme. Und hoffe dann darauf, dass ich dank funktionierender Therapie und gesunder Lebensweise mit 80 Jahren fitter bin als meine Klassenkameraden, die über die Stränge geschlagen haben. Das ist meine Hoffnung. Welche Therapieoptionen haben Frauen mit Kinderwunsch, die eine aktive MS haben? Nele Handwerker: Denn da kenne ich mich wirklich nicht aus. Gibt es da Möglichkeiten von den hochwirksamen Medikamenten oder macht es Sinn zumindest auf eine weniger wirksame Therapie zu wechseln? Wie verträgt sich das? Prof. Mathias Mäurer: Genau, man muss da ein bisschen unterscheiden. Also in der Regel ist es so, man sollte stabil in eine Schwangerschaft reingehen, weil man weiß, da ist eine ganz gute Korrelation zwischen der Schubhäufigkeit vor Beginn der Schwangerschaft und dem, was man nach Entbindung zu erwarten hat, wo ja manchmal die Schubhäufigkeit auch etwas steigt. Also wenn man stabil reingeht, ist die Chance, dass man auch stabil rauskommt aus der Schwangerschaft ziemlich gut. Und jetzt muss man unterscheiden, es gibt ja wie gesagt auch moderate MS-Formen, die jetzt gar nicht so eine hohe Entzündungsaktivität haben. Bei denen ist die Schwangerschaft meistens auch ausreichend, um die Medikation zu ersetzen, weil die Schwangerschaft per se ja auch ein bisschen immunsublimierend wirkt. Man muss ja das Kind tolerieren, was ja zur Hälfte vom Vater ist, deswegen reguliert sich das Immunsystem selber runter. Und das führt auch dazu, dass man eben mit zunehmender Schwangerschaft immer weniger Schübe bekommt. Man holt das dann zwar statistisch wieder auf in der Perinatalphase. Aber grundsätzlich, wenn man eine moderate MS hat, kann man eigentlich bis zum Eintritt der Schwangerschaft so ein Medikament nehmen und dann setzen es viele ab und das funktioniert mit der Schwangerschaft ganz gut. Ein bisschen anders ist es, wenn man eine sehr hoch aktive MS hat, die nur mit hoch aktiven Medikamenten stabil ist. Zum Beispiel die Frauen, die unter Tysabri sind, das sind ja meistens Frauen, die eine sehr hochaktive MS haben, denen empfehlen wir heutzutage, das Tysabri auch über die Schwangerschaft zu nehmen. Nur kurz vor Entbindung sollte es abgesetzt werden, um danach gleich wieder zu starten. Auch bei Therapien wie Ocrelizumab, die alle halbe Jahr gegeben werden, kann man eigentlich die Schwangerschaft ganz gut mit den Infusionen planen. Man kann letztlich die Schutzwirkung, die man durch diese zyklischen Infusionen hat, so ausnutzen, dass man auch in der Schwangerschaft noch ganz gut protegiert ist. Auch da haben wir mittlerweile ganz gute Konzepte. Nele Handwerker: Super. Schön. Prof. Mathias Mäurer: Deswegen einfach den Neurologen fragen, wie man da in der individuellen Phase mit Kinderwunsch verfahren kann. Aber unsere Maßgabe ist, wir wollen natürlich jeder Frau, auch mit MS, eine ganz normale Schwangerschaft ermöglichen und natürlich auch ihren Kinderwunsch absolut realisieren lassen. Das war ja früher furchtbar mit den ganzen Verboten, die es da gab. Und ich möchte nicht wissen, wie viele Schicksale da zerstört worden sind mit komplett falschen Empfehlungen. Wir versuchen heute alles möglich zu machen, aber man sollte halt vorher drüber sprechen, wie man das am besten realisiert. Nele Handwerker: Okay, super. Das heißt, es gibt Medikamente, die kann man nehmen. Das finde ich sehr schön. Was passiert denn, wenn ich eine aktive MS mit einer verlaufsmodifizierenden Therapie zum Stillstand gebracht habe und denke, jetzt ist alles gut und jetzt setze ich die Medikamente ab? Nele Handwerker: Das lese ich leider immer mal wieder, auch bei Social Media. So nach dem Motto, jetzt ist es super und jetzt kann ich endlich wieder auf diese, in Anführungsstrichen, bösen Medikamente verzichten. Prof. Mathias Mäurer: Na ja, die Krankheitsaktivität wird wiederkommen. Das kann, wie gesagt, bei einer moderaten MS auch klappen, dass man nicht unbedingt sofort irgendwas bekommt oder dass es lange dauert. Obwohl, wenn man so in Studien guckt, auch Absetzstudien mit Interferonen, merkt man schon, dass eben die Gruppe, die abgesetzt hat, schlechter läuft. Also zumindest im statistischen Mittel. Im Einzelfall kann es natürlich klappen, genauso wie es im Einzelfall auch ziemlich in die Hose gehen kann. mit Einzelfällen kann man sowieso nichts entscheiden. Es wird immer jemanden geben, der sagt, bei mir hat das ganz gut geklappt, aber das kann man eben nicht auf die Allgemeinheit ausrollen. Wenn man aber eine hochaktive Therapie oder eine hochwirksame Therapie stoppt, da kann man ziemlich auf die Nase fallen. An der Stelle sei gesagt, zum Beispiel Patientinnen, die auf Fingolimod sind oder auf den S1P-Modulatoren, wenn die absetzen, die machen halt gerne mal einen Rebound, also das er dann so richtig zuschlägt der Schub. Auch bei Tysabri hat man häufig eine Wiederkehr der Krankheitsaktivität und Rebound-Phänomene. Das Absetzen sollte man in der Tat mit seinem Neurologen sehr gut besprechen und zusammen durchsprechen, wie das persönliche Risiko ist, zumindest statistisch, wenn ich jetzt das Medikament weglasse? Wie gesagt, ich habe teilweise auch diese Beiträge im Internet gesehen. Da gruselt es mir natürlich ein bisschen. Das sind einfach ziemlich dämliche Empfehlungen. Welche Risiken sind mit einem wiederholten Wechsel von Therapie und Therapieabbruch verbunden? Nele Handwerker: Also ich mache jetzt Therapie, weil ich einen Schub hatte und sobald die Aktivität gestoppt ist, höre ich wieder auf damit. Anstatt dankbar zu sein und das weiter zu nutzen, höre ich auf und spiele dieses Ping Pong Spiel. Prof. Mathias Mäurer: Na ja, zum einen gibt es tatsächlich Medikamente, dazu gehören die S1P-Modulatoren, so First Dose Effekte. Das heißt, man bringt sich dann natürlich mit so einem On/Off-Schema auch immer wieder in eine blöde Situation, weil man halt diese First Dose Effekte als Nebenwirkung mitnimmt. Das ist nicht besonders klug bei solchen Medikamenten. Dann ist es natürlich auch so, Medikamente müssen sich auf ein gewisses Steady State einpendeln. Die meisten Basismedikamente zum Beispiel, die brauchen eine gewisse Zeit, bis sie die volle Wirksamkeit entfalten. Also wenn man diese Medikamente drei Monate nimmt, dann absetzt, dann irgendwann mal wieder drei Monate nimmt, dann wird man nie den Effekt haben, den man eigentlich versprochen bekommt durch das Medikament. Deswegen sollte man es so nehmen, wie es auch im Beipackzettel drinsteht. Das haben wir ja am Anfang schon durchgegangen, es geht um eine Art Prophylaxe. Das ist nichts, was die akute Entzündung bremst. Sondern diese Medikamente sind dafür da, um für die Zukunft weniger Entzündungslast auf das Hirn einwirken zu lassen. Das heißt, diese Medikamente sind wie eine Versicherung. Ist ja auch nicht so, dass sie ständig Ihre Reiseversicherung kündigen, wenn sie mal gerade nicht im Urlaub sind. Das macht man ja auch nicht. Man lässt sie weiterlaufen. Und so muss man das auch bei den MS-Medikamenten betrachten. Das ist eine Art Versicherung, die lässt man einfach laufen und freut sich, wenn das gut funktioniert. Und wenn es nicht gut funktioniert, dann kann man nach Alternativen suchen. Und nicht funktionieren können eine mangelnde Wirksamkeit oder zu viele Nebenwirkungen sein. Aber eben keine, aus meiner Sicht, eigenen Ideen verwirklichen. Nele Handwerker: Ja, das bitte für den kreativen Bereich lassen, nicht für die medizinische Behandlung. Prof. Mathias Mäurer: Genau. Nicht kreativ werden mit den Medikamenten. Also, das sage ich auch ärztlichen Kollegen. Das ist auch manchmal so der Fall, dass man sich dann irgendwelche Schemata ausdenkt. Bitte nicht. Welcher Prognose sehen Menschen entgegen, die die MS mit, in Anführungsstrichen, nur einer gesunden Lebensweise eindämmen wollen? Prof. Mathias Mäurer: Ich glaube, das wird nicht funktionieren. Also ich habe überhaupt nichts gegen natürlich diese supportiven Konzepte, gesunde Lebensweise, Achtsamkeit, viel Sport, auch wegen mir, alles mögliche Komplementäre, wenn es guttut, geschenkt. Aber bitte immer als zusätzliches Konzept. Die Basistherapie für jede MS ist, dass man das Immunsystem in seiner Wirksamkeit bremst, in seiner Auswirkung. Und dem Immunsystem ist ziemlich egal, wie sie sich ernähren. Also das ist vielleicht jetzt ein bisschen vollmundig ausgedrückt. Es gibt natürlich schon so gewisse Ideen, was jetzt dem Immunsystem besser und schlechter gefällt, aber sie brauchen da keine speziellen Diäten. Es reicht einfach, wenn man gesunden Menschenverstand walten lässt und eigentlich den Gesundheitsempfehlungen folgt, die eigentlich für alles gelten, wenn man im Leben gut zurechtkommen will. Das ist auch als MS-Patient absolut ausreichend. Aber wie gesagt, wenn jemand Spaß an bestimmten Diäten hat, Spaß an bestimmten Nahrungsergänzungsmitteln, solange es nicht gefährlich ist, ist das von meiner Seite aus kein Problem. Aber wie gesagt, bitte mit einer vernünftigen Immuntherapie, angepasst an den Schweregrad der Erkrankung. Nele Handwerker: Und eine gegensätzliche Frage: Wie sieht die Prognose von MS-Patienten aus, die eine wirksame Therapie nutzen, wo wirklich die Aktivität komplett unterdrückt wird, auch im subklinischen Bereich? Nele Handwerker: Wo auch die MRTs, keine Aktivität zeigen, möglichst noch ergänzt durch einen gesunden Lebenswandel. Prof. Mathias Mäurer: Ich glaube, dass es denen langfristig wahrscheinlich besser gehen wird. Ich meine auch das kann man jetzt individuell nicht für jeden sagen, weil es gibt in der Tat auch wirklich schon sehr, sehr aggressive Verläufe, wo man auch manchmal der Erkrankung bei bestem Willen auch als Arzt so ein bisschen hinterherläuft. Aber ich sage mal, mit einer normalen MS, die vernünftig behandelt ist, erzielen wir schon heute doch ganz gute Verläufe. Wenn ich mir zum Beispiel jetzt Daten angucke, was die Transition in diese sekundär chronisch progrediente Erkrankungsphase angeht, da gibt es ja noch diese alten Daten, die auch noch in den alten Lehrbüchern drinstehen und meistens auch in irgendwelchen Ratgebern, dass so nach zehn Jahren doch 50 % eben eine sekundäre, chronisch progrediente Verlaufsform auch in Kauf nehmen müssen. Also die letzten Daten, die ich gesehen habe, die das systematisch ausgewertet haben, also nach der Ära der Immunmodulatoren, die ist mittlerweile schon weit unter 20 %. Und wenn man hochwirksame Therapien anguckt, kann man sogar das noch weiter drücken, sogar in den einstelligen Bereich. Und die Studie, die Sie eben angesprochen haben, Dänemark/Schweden, die zeigt ja auch, dass man letztlich Progression durch eine frühe, konsequente Therapie ganz gut verhindern kann. Und dann gibt es auch noch einige Registerauswertungen, die zeigen, dass es von Vorteil ist, je früher man anfängt mit der Therapie, desto weniger wahrscheinlich eben den Übergang auch in so progressive Phasen zu erleben. Es gibt schon einige, wirklich gut gemachte Daten, die zeigen, dass das vernünftig ist da auch was zu machen. Noch mal, im Endeffekt ist es natürlich immer die eigene Entscheidung. Und wenn die eigene Entscheidung auf der Basis von Wissen und Evidenz getroffen ist, ist das alles in Ordnung. Ich würde dann zwar auch versuchen, dagegen zu argumentieren. Aber da kann ich gut mit umgehen, wenn ich jemanden gegenüber habe, der mir letztlich evidenzbasiert versichert, dass er das verstanden hat, wie MS funktioniert. Wo ich aber, wie gesagt, gar nicht mit kann, das ist mit irgend so einem Geschwurbel, wo ich merke, da hat sich eigentlich niemand die Mühe gemacht, sich mal damit auseinanderzusetzen, was das eigentlich bedeutet und dass das eben doch eine chronische Erkrankung ist, die auch nicht zwischen den Schüben weg ist. Sondern die ist da und die ist auch bei den meisten aktiv da und es lohnt sich, diese Aktivität auch langfristig gesehen zu unterdrücken. Wie umkehrbar sind Spätfolgen, die sich im progredienten Verlauf der MS zeigen, nach aktuellem Stand der Forschung und Behandlungsoptionen? Nele Handwerker: Vielleicht gibt es ja irgendwelche Leute, die denken, ach und dann erfindet die Forschung was in zehn Jahren und dann kann das alles wieder rückgängig gemacht werden, mein Gehirn wird wieder größer, alles wird wieder toller. Und ich kann hüpfen wie ein Kind. Prof. Mathias Mäurer: Da wird natürlich dran gearbeitet und das ist auch eine große Hoffnung. Das wünschen sich ja viele, dass man die Sache wieder reparieren kann. Irgendwelche Remyelinisierungsstrategien oder auch Neuroprotection oder vielleicht sogar auch ein Wiederaufbau mit Stammzellen oder so. Klar, da wird dran geforscht. Nur da muss man ganz klar sagen, das ist noch so weit weg von einer klinischen Realität, dass ich da nicht drauf warten würde. Da geht nämlich viel Zeit ins Land. Also natürlich ist das mal ein Ziel, dass man eben auch denjenigen helfen kann, die durch die Erkrankung ernst zu nehmende Symptome bekommen haben. Aber im Moment können wir das nicht zurückdrehen. Was passiert ist, ist häufig dann auch fixiert. Man kann das zwar durch Reha auch kompensieren, das Gehirn ist ja wirklich sehr leistungsfähig, auch sogar in späteren Phasen der Erkrankung kann man da noch viel durch Kompensation erledigen. Aber man wird bestimmte Dinge nicht zurückdrehen können oder hat auch noch keine Möglichkeiten in der Hand, das zurückzudrehen. Das erfolgreichste Konzept ist in der Tat eben die frühe entzündungshemmende Therapie. Das ist das, wo wir eigentlich doch in den letzten Jahren gesehen haben, das hat eine ganze Menge Fortschritt gebracht bei der Erkrankung. Nele Handwerker: Jetzt sind Sie schon eine Weile MS-Spezialist. Sind Ihnen denn schon Patienten begegnet, die ihre frühere Entscheidung gegen verlaufsmodifizierende Medikamente bereut haben? Prof. Mathias Mäurer: Ich mache das jetzt seit fast 25 Jahren, dass ich in der MS-Ambulanz arbeite und ich habe wahrscheinlich schon mehrere 1000 Patienten gesehen. Ich bin niemand, der zurück guckt. Natürlich denkt man sich manchmal, Mensch, das hätten wir besser machen können oder hätten wir irgendwie ein bisschen früher begonnen. Aber das interessiert mich eigentlich in so einer Situation nicht mehr. Ich nehme jeden so, wie er kommt und versuche das Beste rauszuholen. Dieser Blick zurück, der ist sowohl von Arztseite Schwachsinn als auch von Patientenseite. Sie können es ja nicht mehr ändern. Der Blick muss immer nach vorne gehen und da muss man die Situation so nehmen, wie sie zu dem Zeitpunkt ist. Ich bin auch der Meinung, man kann, egal zu welchem Zeitpunkt und in welcher Phase immer irgendwas rausholen. Sei es durch Reha, sei es durch symptomatische Therapie und natürlich auch wenn in frühen Phasen vielleicht dieser Sinneswandel passiert dann auch noch durch eine gut gewählte Immunmodulation. Ich sage mal so, ich habe noch keinen MS-Patienten erlebt, der, wenn er sich auf das eingelassen hat und nicht so ein Grundmisstrauen gegen uns als Mediziner mitbringt, der nicht verstanden hat, was wir ihm damit sagen wollen und der dann auch selber sagt, ja, das sehe ich irgendwo ein, das überzeugt mich. Häufig ist es tatsächlich diese Situation, wenn man sich überhaupt nicht auf unsere Sichtweise der Dinge einlässt, sondern nur stur auf auf seinem Modell beharrt, das man dann wahrscheinlich falsche Berater hat, denen man eben mehr vertraut als den Profis. Nele Handwerker: Vielen Dank, war ein tolles Interview. Möchten Sie den Hörerinnen und Hörern noch was mit auf den Weg geben zum Schluss? Prof. Mathias Mäurer: Ich sage mal so: Bleiben Sie in dem, was Sie tun entspannt, aber nicht so entspannt, dass Sie den Kopf in den Sand stecken und denjenigen hinterherlaufen, die Ihnen das Blaue vom Himmel herunter versprechen. Die Erkrankung ist saublöd und letztlich erfordert das auch, dass man sich damit auseinandersetzt und teilweise in manche saure Äpfel beißt oder manche Kröten schlucken muss. Aber irgendwelchen falschen Propheten hinterherzulaufen mit Heilversprechen, das ist auf lange Sicht nicht gut. Nele Handwerker: Ein sehr gutes Schlusswort. Prof. Mathias Mäurer: Ja, das würde ich mitgeben. Nele Handwerker: Vielen, vielen Dank, Herr Professor Mäurer, das war ein tolles Interview. Ich freue mich und ich hoffe, ich darf Sie noch mal irgendwann zu einem schönen Thema einladen. Nochmals danke. Prof. Mathias Mäurer: Immer gerne. Hat mich auch gefreut. Und auch an alle Hörer und Leser noch einen schönen Tag. Nele Handwerker: Tschüss. Prof. Mathias Mäurer: Tschüss. ++++++++++++++++++++ Ich wünsche Dir bestmögliche Gesundheit, Nele Mehr Informationen rund um das Thema MS erhältst du in meinem kostenlosen MS-Letter. Hier findest Du eine Übersicht über alle bisherigen Podcastfolgen.

Host: Jacqueline Nicholas, MD, MPH Ever had a multiple sclerosis (MS) patient who needed to start a DMT? Listen to Dr. Jacqueline Nicholas, System Chief of Neuroimmunology and Director of MS Research at Ohio Health, and Kim, a patient who has been living with MS for seven years, share their experiences with the treatment decision process, including benefit-risk considerations, treatment goals, and patient preferences. They talk about the process for starting and continuing treatment with TYSABRI® (natalizumab) and how Biogen Support Services can help. Please see Important Safety Information, including Boxed Warning for PML, below.

Host: Jacqueline Nicholas, MD, MPH Ever had a multiple sclerosis (MS) patient who needed to start a DMT? Listen to Dr. Jacqueline Nicholas, System Chief of Neuroimmunology and Director of MS Research at Ohio Health, and Kim, a patient who has been living with MS for seven years, share their experiences with the treatment decision process, including benefit-risk considerations, treatment goals, and patient preferences. They talk about the process for starting and continuing treatment with TYSABRI® (natalizumab) and how Biogen Support Services can help. Please see Important Safety Information, including Boxed Warning for PML, below.

Alissa Frazier was in college when she first began experiencing odd symptoms. She felt an electrical-type shock run down her neck along her spine and developed optic neuritis. Plus she had aches and pains that seemed odd for someone in her early 20s. After extensive testing, doctors diagnosed her with the autoimmune disorder, multiple sclerosis, or MS. To manage symptoms, she tried daily injections and then Tysabri. They both helped but she still experienced considerable fatigue and pain. Then she recalled that, a few years earlier, going gluten-free had helped her symptoms. This time she decided to go further with diet, choosing to follow the autoimmune protocol (AIP) diet and an elimination diet to reduce the inflammation associated with MS. Within a few months, her pain and fatigue had stopped. These days, Alissa relies on a paleo diet, plus avoids some specific trigger foods, such as nightshades, to help keep her MS symptoms at bay. Alissa's health turnaround inspired a career change. She's now a Licensed Mental Health Counselor, Certified Personal Trainer, Nutritional Therapy Practitioner and AIP Certified Coach. She works with individuals 1:1 either remotely or in-person who have multiple sclerosis and other neurological disorders. She uses real food and anti-inflammatory lifestyle coaching to help individuals improve their symptoms, feel better in their skin and create a lifestyle that improves their health and leads to a life they love.  Now that she has the energy to do so, she loves being outdoors and can usually be found hiking or lifting weights. In my conversation with Alissa, you'll hear… The multiple sclerosis diet, including the autoimmune protocol diet (AIP), that helped stop fatigue and pain How her diet has evolved over time The role of exercise in keeping her body strong Why vagus nerve exercises are particularly helpful for Alissa and those with MS Other practices that keep her symptoms in check, including lymphatic work, meditation and breathwork Her advice for others with MS or other neurological conditions   You can find more information about Alissa at www.liss-ms.com/. She's on Instagram at https://www.instagram.com/liss.ms/.   The episode web page: https://rebuildingmyhealth.com/multiple-sclerosis-diet   Listen to Rebuilding My Health Radio wherever you find your favorite podcasts… Apple Podcasts, Stitcher, Google Play, Alexa, Spotify, and much more! If you enjoyed this episode, we truly appreciate your subscribing/following, rating and reviewing it. It helps tremendously with others finding our podcast. Get a copy of our free guide, 4 Ways to Ease, Reverse or Even Eliminate Chronic and Complex Illnesses: https://rebuildingmyhealth.lpages.co/landing-page-for-4-ways-to-ease-reverse-or-eliminate-chronic-illness/ Follow Rebuilding My Health: Facebook – https://www.facebook.com/rebuildingmyhealth Instagram - https://www.instagram.com/rebuildingmyhealth/ Pinterest - https://www.pinterest.com/rebuildingmyhealth ------------ Podcast Produced by Sonorous Laboratory

Welcome to Living Well with MS Coffee Break #26, our season 3 finale, where we are pleased to welcome Pat Feller as our guest!   Our Coffee Break series is your chance to get to know members of our diverse OMS community. In each episode, you'll join Geoff Allix for an intimate chat with a different member of our global community. Our guests will share their personal stories and talk about their challenges and victories, large and small. We hope you find common cause and a source of inspiration from the stories of these very special people.   As always, your comments and suggestions are always welcome by emailing podcast@overcomingms.org. We hope you enjoy this episode's conversation with Pat, coming to you straight from sunny San Diego, California.   Pat's Bio:   Pat was born in Southern California to great parents who were both public school educators. His younger brother kept him on his toes. His parents also adopted Pat's other sibling from Vietnam. Pat traveled a lot in his early adult life: he lived in France, Taiwan, Hong Kong, and earned his MBA in Vancouver, Canada. Pat launched a career in the investment management industry, married his beautiful wife Alice, and raised two incredible daughters.     Pat was diagnosed with MS at the end of 2017.  The beginning of this MS journey was very hard. He couldn't work.  His typically high energy was gone.  Depression, anxiety, and identity confusion struck.  At the beginning, he was very influenced by the work of Roy Swank, Bob Cafaro, and a Facebook group centered on approaching MS in natural ways.  After two years of rest, he tried to return to work as a financial advisor.  After one year, it was clear that it wasn't a good fit, and a normal work week was out of the question.     In the past year, Pat's neurologist updated his diagnosis from RRMS to PPMS.  Pat tries not to let this affect his mindset.  He works hard to be positive in his internal and external voice.  His new "raison d'etre" is to be a blessing to others.  In that spirit, his MS journey has also strengthened his Christian faith.     Pat discovered OMS a few years ago.  Dr. Jelinek's words were in fact very influential in his decision early on to discontinue Tysabri.  Through much of his MS journey, Pat tried to distance himself from the MS world.  But this year, he decided to give back to the MS community by becoming more involved.  This has been greatly facilitated by OMS facilitator Phil Startin, whom he got to know in a volunteer PPMS group Phil started.  Phil helped Pat get involved with OMS and to learn that community is super important.  And the OMS community is a great one to be a part of!             Three Important Lessons Pat Learned and Wants to Share:   My riches now are not monetary but in the form of blessings. I have become acutely aware of the connection between health and wealth. I have found that the most important ingredient to managing an MS journey is mindset.   Pat's Links:   Check out Pat's profile on LinkedIn, where he has started a dialogue on the health-wealth connection and its importance to the economy and personal finances. Check out Pat's Instagram Pat recommends this TED talk by Bob Cafaro, a cellist with the Philadelphia Symphony who was himself diagnosed with MS and achieved very good results with a protocol very similar to OMS.   Pat loves this interview with the incredible Dr. Siray Stancic MD, who was diagnosed with MS and discovered the power of lifestyle medicine, which is what OMS is about.     Coming up on our next episode:   This is our final episode for 2021, so take a breath and exhale the year that was to make space for a happier and healthier 2022. Living Well with MS, Coffee Break, and Ask Jack will return with new episodes beginning in January 2022. And it will be a special year at that, because not only will it mark our 4th season of the podcast, but we'll be celebrating OMS's 10th anniversary! Stay tuned for more info on our Season 4 launch date and thank you for being part of our podcast and OMS communities!   Don't miss out:   Subscribe to this podcast and never miss an episode. You can catch any episode of Living Well with MS here or on your favorite podcast listening app. Don't be shy – if you like the program, leave a review on Apple Podcasts or wherever you tune into the show. And feel free to share your comments and suggestions by emailing podcast@overcomingms.org.

As Chief Medical Officer Dr. Ticho is responsible for Stoke's efforts to develop first-in-class RNA based disease-modifying medicines to treat severe genetic diseases. He is also co-founder and former CEO of Verve Therapeutics which is developing therapies to edit the genome and confer protection from cardiovascular disease. Prior to joining Stoke Barry was Head of R&D for Cardiovascular and Metabolic Diseases at Moderna Therapeutics. He was previously Head of External R&D Innovation for Cardiovascular and Metabolic Diseases at Pfizer. Prior to that he was Vice President of Clinical Development at Biogen where he led clinical development for the Tysabri program for MS and led the aducanumab program for Alzheimer's Disease. Barry obtained his M.D. and Ph.D. degrees from the University of Chicago and completed Pediatrics training at Northwestern University and a Cardiology fellowship at Children's Hospital in Boston. He was on clinical staff at Harvard Medical School and Massachusetts General Hospital.

In Folge #111 vom MS-Perspektive Podcast interviewe ich Melanie alias @melsworldinpicutres. Wir kennen uns von Instagram, wo Melanie über ihr Leben mit Multipler Sklerose schreibt, aber auch über all die Freuden des Lebens.  Hier geht es zum Blogbeitrag: https://ms-perspektive.de/interview-mit-ms-patientin-melanie-alias-melsworldinpictures/ Vorstellung Melanie ist verheiratet, hat eine Tochter und zwei Söhne und ist außerdem Hundemama. Sie lebt in ihrer Wahlheimat Schweiz und erblickte einst in Deutschland das Licht der Welt. Diagnose und aktueller Status Seit wann hast du die Diagnose? Seit 2014. Einen Tag nach meinem 33. Geburtstag konnte ich meinen Sohn nicht mehr tragen, war sehr schwach und durcheinander, habe gefüllt gelallt. Einen Tag später konnte ich nicht mehr leserlich schreiben. Da bekam ich Angst und rief den Hausarzt an. Ich solle augenblicklich vorbeikommen. 15 Minuten später hatte ich die Diagnose MS und hing am Kortisontropf. Wie hast du die Diagnose aufgefasst? Und wie war es für deine Liebsten? Mein Mann war dabei. Wir hatten davor noch nie etwas über MS gehört. Es war ein großer Schock für alle Familienmitglieder. Welche Behandlung wurde Dir zu Beginn der Diagnose empfohlen und bist Du der Empfehlung gefolgt? Zu diesem Zeitpunkt habe ich meinem Arzt voll und ganz vertraut. Er empfahl das neueste Medikament Tecfidera. Morgens und abends eine Tablette. Zwei Wochen dann war Schluss. Ich habe es nicht vertragen. War bei Dir ein Wechsel auf andere verlaufsmodifizierende Therapien nötig? Wenn ja, warum? Ich wechselte zu Tysabri. Dies vertrug ich gut. Allerdings blieb die MS sehr aktiv, und ich bekam zusätzlich alle 3-4 Monate Kortison. 18 Gaben und Monate später war mein JC Virus zu hoch und ich musste aufhören. Ich hatte in dieser Zeit keine neuen Läsionen, die Herde im Kopf waren immer die selben, nur ständig aktiv. Warst Du mal bei einer Reha wegen der MS oder nutzt Du symptomatische Therapieangebote im Alltag? Wenn ja, wie zufrieden bist Du damit? Zu Neujahr 2020 war ich nach einem großen Schub und Herd am Sehnerv drei Wochen in der Reha. Seitdem bin ich bei der Physiotherapie und Ergotherapie. Die Spitex Schwester kommt einmal die Woche vorbei. Ich war acht Monate bei einem Psychologe,. der dann jedoch in Babypause ging. Deshalb wechselte ich in eine psychosomatische Gesprächstherapie. Nach sechs Monaten wechselte meine Therapeutin ihre Arbeitsstelle. Bisher bin ich noch nicht wieder bereit mich schon wieder auf jemanden neues einzulassen.  Dennoch haben mir die Therapien sehr geholfen und tun es noch. Wie kam es dazu, dass Du so offen über Deine Gefühle und Deinen Weg mit der MS schreibst? Das war zu Beginn gar nicht meine Absicht. Aber vor fünf Jahren hast du nicht viel über die MS gefunden, zumindest keine Erfahrungsberichte. Ich wollte einfach darüber schreiben und es hat mir sehr gut getan und beim eigenen Verarbeiten geholfen. Leben, Beruf und Hobbies In welcher Lebensphase hast Du die MS-Diagnose erhalten und hat es deine Pläne über den Haufen geworfen? Wir waren gerade das zweite Jahr in der Schweiz. Mein Kleiner wurde vier Jahre alt und mein Zweiter eingeschult. Ich war mit Muttersein und Kindererziehung beschäftigt. Hausfrau aus Leidenschaft. Die MS hat also nichts über den Haufen geworfen. Deine Bilder bei Instagram sind persönlich, oft lustig und heben die Laune, trotz teils ernster Themen. Wie gelingt Dir das? Ich bin einfach authentisch. Gefühle sind da um gelebt zu werden. Die guten wir die schlechten, trotz MS, trotz depressiver Phasen. Das Leben ist schön! Was magst Du an der MS-Community bei Instagram? Das starke Gefühl niemals allein zu sein. Welche Rolle spielt die MS in deinem Leben und wie wirkt sie sich auf deine Familien, deinen Beruf und deine Freizeitgestaltung aus? Eine sehr große Rolle. Ich arbeite seit zwei Jahren nicht mehr, warte aktuell auf meine Rentengutachten. Die Termine sind im Dezember. Meine Kinder kennen mich nicht anders. Gesellschaftliche Verpflichtungen machen mir Riesenmühe, wie jedes Familientreffen. Tipps Was war dein tiefster Tiefpunkt mit der MS und wie hast du dich wieder empor gekämpft? Unser Familienurlaub 2015 in Ägypten. Da lernte ich die MS mit allen Tücken kennen, bis hin zum nicht laufen können. Geht nicht – jetzt erst recht. Was machst du, wenn du Symptome der MS verspürst? Symptome sind ja ständig da. Mittlerweile kann ich sie gut einschätzen und reagieren. Wünsche und Ziele Gibt es einen großen unerfüllten Wunsch? Nein, ich bin wunschlos glücklich. Welche Entwicklung wünschst du Dir im Bereich der MS in den kommenden 5 Jahren? Noch bessere Therapien. Und das aus unheilbar ein heilbar wird. Das wäre wünschenswert. Blitzlicht-Runde Was war der beste Ratschlag, den du jemals erhalten hast? Positiv denken bedeutet, dass du dich für Gedanken entscheidest, die dir Kraft geben! Wie lautet dein aktuelles Lebensmotto? Es gibt keine falschen Entscheidungen, aus Fehlern lernt man. Mit welcher Person würdest du gern einmal ein Kamingespräch führen und zu welchem Thema? Mit niemand bestimmten. Vervollständige den Satz: „Für mich ist die Multiple Sklerose… “ …stark mit meinen Emotionen gekoppelt. Welche Internet-Seite kannst du zum Thema MS empfehlen? TrotzMS und natürlich MS-Perspektive. Welches Buch oder Hörbuch, das du kürzlich gelesen hast, kannst du uns empfehlen und worum geht es darin? „Klartext Ernährung“ von Dr.med. Petra Bracht. Es geht um Antworten, wie Lebensmittel vorbeugen und heilen. Abschlussrunde Hast du einen Tipp, den du deinem jüngeren Ich geben würdest, für den Zeitpunkt der Diagnose? Es wird nichts passieren, wo du dich nicht wieder raus kämpfst! Möchtest du den Hörerinnen und Hörern noch etwas mit auf dem Weg geben? Als Msler ist es dringend erforderlich auf seine Bedürfnisse zu hören und lernen nein zu sagen. Wo findet man dich im Internet? Bei Instagram unter @melsworldinpictures ———- Vielen Dank für das geführte Interview an Melanie und die emotionale und positive Grundstimmung! Bis bald und mach das beste aus deinem Leben, Nele Mehr Informationen und positive Gedanken erhältst Du in meinem kostenlosen Newsletter. Hier findest du eine Übersicht zu allen bisher interviewten MS-Patienten.

SUMMARY: In this episode, I welcome board certified neurologist, Dr. Marwa Kaisey, to the podcast where we discuss the most up-to-date information on COVID vaccines and COVID boosters. In particular, we discuss how all of that information relates to people living with MS. Dr. Kaisey, an assistant professor in the Department of Neurology at Cedars-Sinai Medical Center in Los Angeles focuses her practice on caring for people with MS and other neuroimmune conditions. She teaches Cedars-Sinai neurology residents in both inpatient and outpatient settings and assists with the MS fellowship. She's won multiple teaching awards including the AB Baker teacher recognition award from the American Academy of Neurology. Dr. Kaisey is active in research and has several publications on the diagnosis and misdiagnosis of multiple sclerosis. Her work includes developing novel tools to more quickly and accurately diagnose MS. She can be found on Instagram @themsmd and YouTube where she provides, in a quick and concise way, all the latest in MS research as well as tips for living well with MS. Links to both of those can be found in the Episode Notes. In this episode, Dr. Kaisey and I cover not only the most commonly asked questions regarding COVID and MS, but also the questions that we might be curious about but aren't often discussed. EPISODE NOTES: - Is MS alone considered an underlying condition? - Which MS treatments put you at higher risk? - What about the timing of a vaccine and your infusion? - Which MS drug puts you at 4x higher risk of being hospitalized from Covid? - Tysabri and the blood brain barrier. - The sweet spot for timing your vaccine and your infusion for best vaccine efficacy. - Vaccine response and antibody testing. - Will the vaccine evolve as new variants emerge? - How the vaccine was designed. - What to do if you want to get a Covid vaccine and a flu vaccine and when? Can you get them at the same time? - Typical side effects of first and second doses of the COVID vaccine. - Dr. Kaisey's Conquer MS project. Link below. - Should an MS patient get a vaccine booster? - A third dose or a booster? Which one? Is there a difference? Are you eligible? - How long does your natural immunity last if you've had COVID? - Mixing brands of vaccines. Is it safe? - How were they able to bring the COVID vaccine to market so quickly? Did they cut corners? Were safety measures sidestepped? - How long until we'll have some sense of normalcy? - Masks. Are they still important? LINKS: Where to find Dr. Marwa Kaisey: Instagram - @themsmd YouTube - https://youtube.com/c/drmarwakaisey Sign up for updates on Dr. Kaisey's Conquer MS Course The MS Gym Instagram - @themsgym Website - www.themsgym.com Facebook - https://www.facebook.com/groups/TheMSGym/?ref=share Brooke Slick Instagram - @brooke.slick Website - www.brookeslick.com

Alexandria was a science teacher and a realtor. Typical MS overachiever. One day she completely lost her ability to walk, speak, and see. How does she go from this to being on point shoes? So glad I was able to talk with this thriver! Join me as I chat it up with Alex.  Instagram: @alexandriagem007 www.thrivingoversurvivingpodcast.com @thrivingoversurvivingpodcast

Alexandria was a science teacher and a realtor. Typical MS overachiever. One day she completely lost her ability to walk, speak, and see. How does she go from this to being on point shoes? So glad I was able to talk with this thriver! Join me as I chat it up with Alex.  Instagram: @alexandriagem007 www.thrivingoversurvivingpodcast.com @thrivingoversurvivingpodcast

Just a few weeks ago, life sciences company Abata Therapeutics came out of stealth mode, unveiling a $95 million dollar investment in a novel cell therapy to treat progressive MS. Joining me to talk about this potentially transformational treatment for progressive MS are the President and CEO of Abata Therapeutics, Samantha Singer, and Dr. Richard Ransohoff, one of the company's co-founders as well as its Chief Medical Officer. We'll also give you a sneak peek at a study that measured the impact of COVID-19 on people with MS in New York City. We'll tell you about a study that examined the viability of at-home Tysabri infusions. We'll share the details of the Can Do MS virtual programs that are happening all month long. And we'll let you know how you can attend Dawnia Baynes's celebration for the entire MS community (did we mention that it's taking place in a very cool virtual world?!!!). We have a lot to talk about! Are you ready for RealTalk MS??! Abata Therapeutics unveils potentially transformational cell therapy for progressive MS  :22 Study measures effects of COVID-19 on people with MS in New York City   11:18 Study examines the viability of at-home Tysabri infusions   14:26 Can Do MS virtual programs for August  16:04 Award-winning MS activist and support group leader Dawnia Baynes is throwing a party -- and you're invited  17:51 Share this episode  30:44 Download the free RealTalk MS app for your iOS or Android device  31:12 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/205 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.com Phone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com National MS Society COVID-19 Vaccine Guidance for People Living with MS https://www.nationalmssociety.org/coronavirus-covid-19-information/multiple-sclerosis-and-coronavirus/covid-19-vaccine-guidance Abata Therapeuticshttps://abatatx.com/ STUDY: Home Infusions of Natalizumab for People with Multiple Sclerosis: A Pilot Randomised Crossover Trialhttps://onlinelibrary.wiley.com/doi/10.1002/acn3.51410 Can Do MS August Program Info and Registration https://cando-ms.org/programs Dawnia's "15" Celebrationhttps://15presentedbybrightside365.eventbrite.com Join the RealTalk MS Facebook Group https://facebook.com/groups/realtalkms Download the RealTalk MS App for iOS https://itunes.apple.com/us/app/realtalk-ms/id1436917200 Download the RealTalk MS App for Androidhttps://play.google.com/store/apps/details?id=tv.wizzard.android.realtalk Give RealTalk MS a rating and review http://www.realtalkms.com/review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 205 Guest: Samantha Singer, Dr. Richard Ransohoff, Dawnia Baynes Tags: MS, MultipleSclerosis, MSResearch, MSSociety, AbataTherapeutics, RealTalkMS Privacy Policy

Multiple Sclerosis News Today's columnist Jenn Powell, discusses a new study assessing the effects of Tysabri on cognitive fatigue. Multiple Sclerosis News Today's columnist Jessie Ace reads an article by Jennifer Powell where she discusses how meditation manages the symptoms of secondary progressive MS. ===================================== Treatment for Relapsing MS Progression | MAYZENT® (siponimod) Read about MAYZENT, a once daily pill that can significantly slow down disability progression in people with relapsing MS. See full prescribing & safety info. https://www.mayzent.com/?utm_source=changeinrms&utm_medium=vanityurl&utm_campaign=novartis_mayzent_2020&utm_content=soundcloud ===================================== Are you interested in learning more about multiple sclerosis? If so, please visit: https://multiplesclerosisnewstoday.com/ ===================================== To join in on conversations regarding multiple sclerosis, please visit: https://multiplesclerosisnewstoday.com/forums/

Yednock relates the discovery and development, over 15 years, of the drug Tysabri, an alpha4 integrin antibody, as a treatment for multiple sclerosis. In the first of his two talks, Ted Yednock begins with an overview of multiple sclerosis.  He describes how, in MS, immune cells are able to transverse the wall of blood vessels and infiltrate the brain and central nervous system resulting in damage to the myelin surrounding neurons.  Yednock and his colleagues hypothesized that by blocking the infiltration of immune cells into the brain, the progression of the disease might be slowed.  They went on to identify alpha4 integrin as the molecule that mediates adhesion of immune cells to the blood vessel wall, and they found that an alpha4 integrin antibody (Natalizumab or Tysabri) could block infiltration of the blood cells into the brain in a animal model of MS.  Yednock then details the clinical development of Tysabri through to its approval by the FDA in 2004.

Just a few months after Tysabri was approved for MS treatment, two patients developed progressive multifocal leukoencephalopathy (PML), a fatal or seriously debilitating disease.  In his second talk, Yednock describes the response of medical and regulatory groups and researchers to this discovery and its impact on the treatment of MS patients with Natalizumab/Tysabri.

And You thought the exorcist was scary... --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/rex-penland/support

EP31 Wolverine Doop 2003, A + X Iron Fist and Doop 2013, All New Dppo 2014 #1-5. MS talk about sick or lazy, the love of pets, motor skills and Tysabri curiosities. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/kevin-kleinhans/message Support this podcast: https://anchor.fm/kevin-kleinhans/support

In Honor of MS Month Evidence to Excellence: News In Neuroplasticity and Rehab talk Multiple Sclerosis. Host Polly Swingle and her guests Director Sonda Rossman, Dietician Katelynne Parisek, Chief Strategy Officer Jennifer Butterfield and Nurse Practitioner Sarah Johnson all of The Michigan Institute for Neurological Disorders (MIND) bring awareness to what some would call an “Invisible” disease.Host:POLLY A. SWINGLE , CEO & Co-OwnerPolly joined the Recovery Project in 2003, after graduating from Ohio University in 1986 with a BS in Physical Therapy. Her accreditations and certifications include: Neuro development treatment – adult (NDT), Geriatric clinical specialist, Burdenko, Registered yoga instructor and certified exercise expert in the aging adult. Before coming to The Recovery Project, Polly was the Director of Outpatient Services at The Rehab Institute of Michigan and the Director of Rehab Services at Good Samaritan Medical Center. She was recognized as Crain’s Healthcare hero in 2016, MDA Clinician of the Year in 2015 and Clinical Instructor of the year in 2007. Guests:Sonda Rossman, MA, LLPC Director, MS Center – Research & ServicesAs MIND’s MS Center Research Director, Sonda leads the implementation of our expanding, multimodal and cross-disciplinary research programs, and supports our network development with outside collaborations on a national level. Sonda and her team kicked off research with clinical trials for Tysabri.(ta sa bri) MIND now has some of the most novel therapies available for clinical trials and are excited about future breakthroughs for MS therapy. Sonda’s passion for advancing the care for MS patients stems from her own experience with the disease, being diagnosed in her 20’s. Through her efforts, MIND’s MS Center and MS Research has grown into one of the largest private centers available in the country.Katelynne Parisek, MS, RD Registered Dietitian, MS CenterKatelynne is the Registered Dietitian for MIND. With a Master’s degree in Dietetics, she has always had a passion for helping others achieve happiness through healthy eating and lifestyle changes. Katelynne started and implemented a nutrition program focused around symptom management and prevention measures for patients living with autoimmune, inflammatory, and neurological conditions. Working side-by-side, she helps these patients create attainable goals, designs a meal plan to reach these goals, and provides them with all the skills and knowledge necessary to be successful. Katelynne’s main goal is to help her patients feel in control of their life and take the stress away from eating.Jennifer Butterfield, RN BSN MBA Chief Strategy Officer, MINDJennifer is the Chief Nursing and Strategy officer for MIND. She has been a nurse for over 20 years and is the former CEO for two of Surgery Partner’s facilities Lakes Surgery Center and Michigan Surgical Hospital. Jennifer is a certified Administrator and is actively involved in several organizations for improving national healthcare guidelines. Under Jennifer’s direction, MIND is working towards increasing community outreach for the practice and expanding their MS/Neurology specialized infusion centers. MIND now has four (4) infusions centers serving Metro Detroit and the Grand Rapids area.Sarah Johnson, MSN, FNP-BC Nurse Practitioner, MS CenterSarah is the lead Nurse Practitioner for MIND’s Multiple Sclerosis Center. She works directly with Dr. Martin Belkin and Dr. William Boudouris and helped co-found the MS Center’s “MS Wellness Check” program where MIND MS patients receive baseline and yearly follow up testing specific to their MS diagnosis. She is Certified in MS nursing and passionate about making a difference by improving the everyday lives of patients with MS.

People who live with Crohn’s disease or ulcerative colitis have more to consider when it comes to the workplace. The cost of inflammatory bowel disease (IBD) means that a comprehensive insurance plan is a must, which may limit job choices. A flare-up or complication that results in absences can lead to poor performance reviews or difficulties with supervisors or co-workers. How can people with IBD cope? Three women who live with IBD, Megan Starshak, Mary Elizabeth Ulliman, and Tina Aswani Omprakash, tell their stories about missing work, being underinsured, and changing jobs while managing IBD. Information discussed in this episode includes Clostridium difficile (C diff), pouchitis, Crohn’s and Colitis Foundation Help Center, IBD and the Americans With Disabilities Act, The Family and Medical Leave Act, and Financial Help for People with IBD. Select pharmaceutical company assistance programs: Cimzia (certolizumab Entyvio (vedolizumab Humira (adalimumab Inflectra (infliximab biosimilar Remicade (infliximab) Renflexis (Infliximab biosimilar Simponi (goliumumab Stelara (ustekinumab Tysabri (natalizumab Xeljanz (tofacitinib Find Megan Starshak on MeganStarshak.com, Twitter, and Instagram. Find Tina Aswani Omprakash on Own Your Crohn’s, Facebook, Twitter, and Instagram. Find Mary Elizabeth Ulliman on Instagram. Find The Great Bowel Movement on Facebook, Twitter, and Instagram. Find Amber J Tresca at AboutIBD.com, Verywell, Facebook, Twitter, Pinterest, and Instagram. Credits: Sound engineering courtesy Mac Cooney. "IBD Dance Party" ©Cooney Studio.

MS News Today's columnist and forums moderator, Ed Tobias, discusses how some patients and neurologists weigh the risks versus benefits of Tysabri. Are you interested in learning more about Multiple Sclerosis? If so, please visit https://multiplesclerosisnewstoday.com/

Susan Carey - My 21st birthday was at one of my infusions! Topics discussed in this episode:First experiencing double vision. Seeing two golf balls and two basketballs, the optometrist asked her to leave the room while her mum was told there was something in the back of her eye. she could have a tumor or multiple sclerosis.    Being officially diagnosed with Multiple Sclerosis - a degenerative health condition at 14A lumbar puncture done by a medical student. (A lumbar puncture is a common test done to diagnose Multiple Sclerosis. It involves extracting some Cerebral Spinal Fluid from between the discs in the spine and testing it) The people in Susan's Irish village sent her Rosary beads, jumpers and mass cards through the post, was this right to send to a 14 year old diagnosed with MS? She was convinced she was going to die! Treatments and Multiple Sclerosis. We discussed the MS drug Avonex and Susan's experience with the injectable drug. She was so terrified that her Father kindly stepped in to help her with it. After this she went onto Tysabri* (natalizumab) and then Lemtrada* (alemtuzumab) - both infusion treatments which means you need to stay in hospital or a few days. With Lemtrada you also need a few days of taking oral steroids before starting the infusion. Susan was told there was not a lot of research done around Lemtrada at the time. The nurse also didn't know what it meant for fertility something which Susan hadn't even thought about yet. She was told to go away and Google it, research everything about it that she could find and come to a decision on her own. Susan tells us about how she spent her 21st birthday in hospital doing an infusion and the doctors and nurses left balloons, cake and gave presents which made it far easier for her to deal with. Focussing on what you can do. Every day with her dad Susan would walk the length of the small pier in her hometown. She managed to do this after the Lemtrada treatment without holding on to anything. While she was in hospital, Susan decided she would not miss out on any of her diet or training programme so she packed herself some meals to have in the hospital and made a gym out of what she could find around the ward, like the stairs. Living through your teenage years without being able to do the things you absolutely lived for. Turning the hospital into a gym so she could keep up her fitness routine - even whilst being attached to an IV drip! Planning and prepping her own meals to take into hospital. There is no limitations around you, you can always work around things. Starting her own fitness coaching business after feeling unfulfilled in life called ‘fit fusion' an inclusive disability fitness program. When the people in your life are supposed to be supportive but just make you feel inferior when you can't do what they want you to do.  A shift.MS takeover made her realise what the hardest part of her illness - family and friends' unhelpful comments, suggestions and advice.  Best advice for coping with Multiple Sclerosis? Suan says to network online with people already talking about their experiences. *Tysabri is an intravenous infusion (drip) once every four weeks to reduce the number and severity of relapses. It reduces the number of relapses by about two thirds (70%), compared to taking placebo.Common side effects include dizziness, nausea, urticaria (a skin rash) and shivering.Treatment with Tysabri may increase the risk of progressive multifocal leukoencephalopathy (PML), an uncommon brain infection that can lead to severe disability or even death.(source: https://www.mstrust.org.uk/a-z/tysabri-natalizumab) *Lemtrada is a disease modifying drug (DMD) for active relapsing remitting MS and very active relapsing remitting MS.You take Lemtrada as an intravenous infusion (drip) in two treatment courses, twelve months apart. It reduces the number of relapses by about two thirds (70%), compared to taking placebo.Common side effects include infusion-related reactions w

This episode is the first in a series where Kathy talks to MSers from around the world about their diagnosis and treatment experiences, to see how they differ from our own. The first guest in the series is Steve Woodward, who lives in England. He and Kathy had a lot of fun recording this, even if some parts were proof that the US and the UK are still "two nations divided by a common language"! Topics covered include: Steve's diagnosis story His experience of treatment through the UK National Health Service or NHS How the NHS is funded and what it means for people with MS Social security benefits and working with a chronic condition in the UK   Resources mentioned in this episode (clickable links): Steve's article about the UK National Health Service Steve's blog It's a Shit Business All of his articles on MultipleSclerosis.net Steve's blogs about applying for Personal Independence Payment (PIP) - part one and part two Steve on Twitter An explanation of the term "Heath Robinson" which Steve uses in the chat! ** Sign up for the FUMS Friday Night 6 Pack at FUMSnow.com. And for more information about Patients Getting Paid, please visit FUMSnow.com/PatientsGettingPaid. **If you get value from the FUMSnow Podcast Show, please consider leaving a rating or review wherever you get your podcasts. Reviews are really important and help to spread the word about what we do. It's quick and easy to do and we have some instructions here. Thanks for your time and support! **Don’t forget to join us on the FUMS Facebook Page and on Twitter at FUMS. Have an idea for a topic or someone to interview? Perhaps YOU?? Send me an email at Kathy@FUMSnow.com. And remember to speak to this stupid disease as it deserves: tell it FUMS every day!!

In this episode of The Dr. Hedberg Show, I interview Dr. Terry Wahls in a discussion about how to heal Multiple Sclerosis.  We had an excellent discussion about how she overcame Multiple Sclerosis, her research into MS, The Wahls Protocol Diet, the causes of MS, how the gut and the microbiome influences autoimmune disease, the Paleo diet compared to the Wahls Protocol and much more. If you have MS or know someone who does, please share this episode and transcript of the interview below.  It may be the turning point for you or a loved one by following The Wahls Protocol. Dr. Hedberg: Well, welcome everyone to the Dr. Hedberg Show. This is Dr. Hedberg, and I'm very excited today to have Dr. Terry Wahls on the show. So, Dr. Wahls is a Clinical Professor of Medicine at the University of Iowa. She's the author of the book, "The Wahls Protocol: How I Beat Progressive MS Using Paleo Principles and Functional Medicine," and also the cookbook, "The Wahls Protocol Cooking for Life: The Revolutionary Modern Paleo Plan to Treat All Chronic Autoimmune Conditions." You can learn more about her work from her website. It's terrywahls.com. That's terrywahls.com. And she hosts "The Wahls Protocol Seminar" every August where anyone can learn how to implement the protocol with ease and success. And she's on social media. You can find her on Facebook, Terry Wahls, M.D., Instagram, Dr. Terry Wahls, and on Twitter, @TerryWahls. And you can learn more about her MS clinical trials by reaching out to her team via this email, it's msdietstudy@healthcare.uiowa.edu, and I will paste that link and e-mail on drhedberg.com in case you wanna contact her that way. So, Dr. Wahls, welcome to the show. Dr. Wahls: Hey. Thank you so much for having me. Dr. Hedberg: Great. So, just for the people out there who don't really know your story, can you tell us a little bit about what you went through and your MS story? Dr. Wahls: Sure. So, I'm an academic internal medicine doc, very conventionally trained and conventionally practicing, being very skeptical of diets, supplements, complementary and alternative medicine. But God has a way of teaching us, so in 2000, I was diagnosed with relapsing-remitting multiple sclerosis on the basis of a history of dim vision 13 years earlier, and a new problem with my left leg. I had lesions in my spinal cord. So, I knew I wanted to see the best people in the country, take the newest drugs, and so I went to the Cleveland Clinic and saw their best people, took the newest drugs, and steadily declined. I'd had one relapse in the next year involving my right hand. And I continued to gradually decline. By 2003, I had declined enough that I now needed a tilt-recline wheelchair. I took Mitoxantrone. I adopted, yeah, actually the year earlier, the paleo diet after being a vegetarian for 20 years, but as I had already mentioned, I did continue to decline and was in the wheelchair, took Mitoxantrone, continued to decline, then took Tysabri, continued to decline, then was placed on CellCept. And at that point, in 2004, it's quite clear to me that I'm likely to become bedridden, quite possibly demented, and quite possibly suffer from intractable pain related to poorly controlled trigeminal neuralgia. And so, I start reading the basic science again, and I began experimenting using a variety of supplements targeting my mitochondria. And what I discovered is that my fatigue is somewhat less, the speed of my decline is slowed, and I'm really immensely grateful because now my docs have told me I have secondary progressive MS, that there's no more spontaneous recoveries, and so I'm grateful just to slow my decline. Now, the summer of '07, I'm so weak I cannot sit up anymore. I have a zero gravity chair, where my knees are higher than my nose. A staff, resident clinic's there. I work in the Institutional Review Board reviewing research protocols that way. And I have another chair at home.

The caregiver's journey doesn't always get paid the proper amount of attention until a family caregiver finds themselves feeling isolated, overwhelmed, drained, and depressed. But it doesn't have to come to that. My guest is Dr. Kate Lorig, lead author of Building Better Caregivers: A Family Caregiver's Guide to Reducing Stress and Staying Healthy. And we're talking about how to go about building better caregivers.     We're also talking about a new MRI technique that may enable doctors to identify MS patients who are at high risk of disease progression and disability, whether Tysabri can improve MS sexual dysfunction, a new film about how an "invisible disease" can impact everyday daily living, and a clinical trial that's looking at whether two popular "MS diets" can improve MS fatigue.   We have a lot to talk about. Are you ready for RealTalk MS? ___________ MRI Technique Associates Iron in Brain with MS Disability  1:44 Tysabri May Be Effective in Treating MS Sexual Dysfunction  4:11 "Hidden" Shows How an Invisible Disease Can Impact Everyday Life  6:05 Clinical Trial to Look at Effectiveness of Diet in Improving MS Fatigue Is Recruiting Participants  8:08 Interview with Dr. Kate Lorig  10:24 ___________ LINKSIf your podcast app doesn’t show these links, you’ll find them in the show notes at www.RealTalkMS.com Brain Iron at Quantitative MRI Is Associated with Disability in Multiple Sclerosis Patient Perceived Changes in Sexual Dysfunction after Initiation of Natalizumab for Multiple Sclerosis Watch "Hidden" on YouTube shift.ms Clinical Trial to Test Dietary Approaches to Treating Fatigue in MS Email Address for University of Iowa Diet & MS Fatigue Study is MSDietStudy@healthcare.uiowa.edu Building Better Caregivers: A Family Caregiver's to Reducing Stress & Staying Healthy Give RealTalk MS a Rating & Review ___________ Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 45 Hosted By: Jon Strum Guest: Dr. Kate Lorig Tags: MS, MultipleSclerosis, MSResearch, tysabri, Hidden, shiftms, terrywahls, wahlsdiet, swankdiet, caregiving, UIowabiomed, RealTalkMS

Relapsing MS with former NHL player Bryan Bickell.What You'll Learn in this Episode: The story of his diagnosis. What relapsing MS entails. How it affects his daily life. How he manages it. The types of lifestyle changes he's made. The medication he takes to manage MS, Tysabri.   High Five Highlights: For someone who is listening who may just have been diagnosed with MS, what would you say to them? Stay positive. When trying to achieve greatness in a sport, what's the most important thing to remember? Remember to have fun. What has having MS taught you? Pay attention to the small things. Tell me about a teammate or coach that inspired you to be better? Marion Hossa Finish this sentence: “Throughout my life the most important thing I've learned is...”  Pay attention to family. Connect with Bryan InstagramTysabri Share the Show! If you enjoyed this show, please rate it on iTunes and write a brief review. That would help us tremendously in getting the word out and raising the visibility of the show. Sponsor: audible.com - get a FREE audiobook download and 30 day free trial at www.audibletrial.com/whichwayislife  

Relapsing MS with former NHL player Bryan Bickell.What You’ll Learn in this Episode: The story of his diagnosis. What relapsing MS entails. How it affects his daily life. How he manages it. The types of lifestyle changes he’s made. The medication he takes to manage MS, Tysabri.   High Five Highlights: For someone who is listening who may just have been diagnosed with MS, what would you say to them? Stay positive. When trying to achieve greatness in a sport, what’s the most important thing to remember? Remember to have fun. What has having MS taught you? Pay attention to the small things. Tell me about a teammate or coach that inspired you to be better? Marion Hossa Finish this sentence: “Throughout my life the most important thing I’ve learned is...”  Pay attention to family. Connect with Bryan InstagramTysabri Share the Show! If you enjoyed this show, please rate it on iTunes and write a brief review. That would help us tremendously in getting the word out and raising the visibility of the show. Sponsor: audible.com - get a FREE audiobook download and 30 day free trial at www.audibletrial.com/whichwayislife  

Bryan Bickell won three Stanley Cup titles while playing with the Chicago Blackhawks during nine seasons in the Windy City before being traded to the Carolina Hurricanes in 2016. It was then that Bickell got a diagnosis that he's continuing to deal with today: relapsing MS, which forced him to retire in April after his season was over. Bickell took three months off after the diagnosis and finally got to play at seasons end. FOX's Gurnal Scott spends "A Few Moments With..." Bickell to discuss life after hockey, what he did with the Stanley Cups after he won with the Blackhawks and how he is dealing with his condition of MS. Follow Bryan Bickell on Twitter: @bbicks29 & FacebookGet more information on TYSABRI by CLICKING HEREFollow Gurnal Scott on Twitter: @GurnalScott Learn more about your ad choices. Visit megaphone.fm/adchoices

[intro music]   Host – Dan Keller Hello, and welcome to Episode Ninety of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller.   Welcome to the weird world of the U.S. pharmaceutical market. A few outrageous cases of drug price gouging have made the headlines, but in multiple sclerosis, a more serious concern is the steady annual rise in cost of all disease-modifying therapies, or DMTs. So says Dr. Daniel Hartung, a researcher at the Oregon State University/Oregon Health and Science University College of Pharmacy. In a recent study, he found that MS drug prices over time outpaced both inflation and similar biologics. It’s not just the new drugs. As each more expensive DMT comes to market, the prices of older drugs also race to catch up. It’s affecting the drugs available to patients and causing other concerns.   Interviewer – Carol Morton Can you tell me what questions you were asking and why?   Interviewee – Daniel Hartung Sure. So the study that we did had its origin after having some conversations with some neurologists at OHSU about increasing frequency of seeing their patients facing larger and larger, not only cost sharing and copays from the insurance companies for drugs for MS, but also increasing restrictions, typically from insurance companies in kind of what medications they were supposed to take first prior to perhaps failing one, then going to another medication for MS. And so this is all kind of happening in the context of what they were seeing as just higher prices for some of these medications.   And so what we decided to do is…no one's really done this…is look at in a systematic way the trajectory of pricing for MS drugs, essentially since their approval until we went through the end of 2013. And to look at what the just general trend was, try to figure out if there were certain specific factors that were associated with higher prices over time, like the approval of newer agents, things like that. That was kind of the general objective of the study.   MSDF And then how did you go about conducting this study? Is it hard to find that data?   Dr. Hartung It can be. So I'm fortunate to have access to some data set that has longitudinal pricing data for pharmaceuticals for the past 30 years or so. And so from my perspective, it wasn't difficult. But essentially we used this data set that collected average wholesale price, as well as wholesale acquisition cost, so kind of the two usual, most common (I'll call them) sticker prices for drugs. And so this data set for all medications, it kind of tracked pricing of medications over time. And so that was the core data set for our analysis.   MSDF And so you pulled the multiple sclerosis disease-modifying therapies out of that. How many did you look at?   Dr. Hartung So in our study we looked at 11 medications for MS. They included the three what are typically called platform therapies that have been on the market for about 20 years now. Those include Avonex, Copaxone, and Betaseron, and just followed them through time, through the approval of several other new agents, like Tysabri. And then there's in the last five to six or seven years, the FDA has approved several agents that can be taken orally, Gilenya, Aubagio, and Tecfidera now. And there was a couple other kind of miscellaneous agents that were kind of variants of the interferons and things like that.   MSDF And then what did you find?   Dr. Hartung Well, there are several interesting things, but I think one of the most striking things is that the prices for the platform therapies, Avonex, Betaseron, and Copaxone, were pretty stable for at least 10 years from their approval in early to mid-90s. And then, essentially what we observed is that new agents that came on the market, starting with Rebif in about 2001, came out, and they were usually priced about 20% to 30% higher than the existing therapies. And what we observed is that when these new agents came out or approved, that these higher prices, the cost or the price of kind of the platform therapies quickly escalated to almost match the price of the newer agents that were approved. And this pattern kind of repeated itself and actually became more intense when the newer oral agents came on the market in the last five or six years.   So the cumulative effect of that is in the early 2000s, Copaxone, Betaseron, and Avonex were priced about $10,000 to $15,000 a year. And at the end of our study, all of the agents that are currently approved were priced between $50,000 and $60,000 per year. And so we tried to quantify kind of the rate of increase and compare that with other kind of benchmarks: inflation, prescription drug inflation. What we found is that the price increase for those agents was well above what you'd expect for not only just general inflation, but also prescription drug inflation.   MSDF MS drugs, the cost of all of them, not just the new ones, are increasing at a rate higher than any other drug category?   Dr. Hartung In addition to looking at kind of standard metrics of inflation, we compared the price increases for the platform therapies to what we considered kind of comparable biologics. So we looked at a class of medications called tumor necrosis factor inhibitors, which are used for immunologic conditions like rheumatoid arthritis. And what we found is that the price increases for the platform therapies for MS increased substantially and significantly above price increases for those medications for the tumor necrosis factor inhibitor. So from our study, from our perspective, prices increased higher than they did for these TNF inhibitors.   We haven't really compared them across other classes of drugs, but there are some new publications that have looked at price increases for other agents, such as in other classes like insulin, drugs for diabetes, and cancer agents as well. The numbers are slightly different, but the trajectories look pretty similar. So in the last, you know, 10 years, there's been almost it seems like a logarithmic increase in the price of many of these agents and classes.   MSDF So is this a case of a system that has incentives that maybe aren't as well matched to patient needs as they should? What's going on here?   Dr. Hartung I mean, that's a good question. Definitely there's a system. The market-based system for pharmaceuticals in the United States is incredibly dysfunctional in that it's very dissimilar from any other kind of consumer market for technology, phones, cars, things like that, where you typically see prices go down after a while. And you don't see that in health care or in drugs. You see just prices increase. And so there's a dysfunction that just kind of is core to the economics of health care.   And then I think there is an element of pharmaceutical industries pricing these agents essentially what the market will bear. Now my opinion is that a lot of the aggressive increases in price were initially seen with some of the cancer agents. And so I think that in that field there is a kind of pushing of the envelope for many anti-cancer drugs that's now has proliferated to other classes of drugs, including MS agents.   The other element that's kind of unclear and adds to the murkiness to this is that, you know, our study and other studies that have looked at what I'm calling pricing of the agents use average wholesale or WAC and with some sort of adjustments for rebates or discounts. So typically third party payers or pharmaceutical benefits managers will negotiate with pharmaceutical industry to lower the cost of the agent for the payer. But all that information is typically proprietary, and so it's really difficult to know what the actual cost of the medication is, unless you're paying cash. If you're paying cash, then the cost is going to be pretty close to the price that's set. So people who don't have insurance are paying the most, and the people with insurance, Medicaid, any sort of governmental insurance, they're paying typically AWP minus a certain proportion or WAC plus a proportion percentage essentially based on the rebate that they get.   So that adds a little bit of kind of uncertainty. Pharmaceutical industry may come back to say that, you know, we're giving pretty good discounts on certain medications in certain payers, but from the data we have and the pricing data, there's just been this aggressive increasing in prices. And we don't know if it's being mitigated by increasing rebates and discounts over time. So it's complicated.   MSDF What do you hope people will do with this information? It does sound like a complicated system that's almost unapproachable for the individual patient or individual doctor. What can people start doing now? Where does the responsibility or responsibilities lie?   Dr. Hartung You know, I think that the data we generated in our study has been useful for some of the advocacy groups in the multiple sclerosis community. So the National Multiple Sclerosis Society has been using it to try to, you know, advocate or perhaps political reforms or some other meaningful reforms in kind of how these things are reimbursed, things like that. Drug prices has been in the news quite a bit over the last several years, and now even more with the election season in full tilt. And so I think a lot of the candidates are talking about potential solutions to the issue.   From the patient's perspective, they're in a real quandary in a sense that even a sharp move with the Affordable Care Act to a lot of high deductible, high cost sharing plans where if your monthly cost of a MS agent is $5,000, you pay 20% of it until you hit your deductible. You know, that's $1,000 at the pharmacy, and that's a pretty big out-of-pocket cost that you face. So I think that there's some, you know, movement in the advocacy groups to try to…especially working with insurance companies to make sure that access is open because these medications are incredibly individualized. And there's not really good predictors of who will respond to each type of medication, and they're all different. Some of them are administered subcutaneously, intramuscularly, orals, and so there's some patient preferences that fall into play here as well as the price. And so I think there's been some movement and some discussion making sure that access to all the agents is relatively easy for patients.   But from a solutions to the pricing situation, you know, I think we're still kind of in discussion phases about what we can do as a country to kind of deal with this issue because it's not exclusive to the MS drugs.   MSDF So what's next with you? Are you following up on this?   Dr. Hartung So from our perspective, the group that I worked with, the two neurologists' project, we just submitted a grant, well, it was in January, that we hope to be competitive and hope to get that's looking at how these high drug prices actually affect patients in terms of their medication taking and potentially adverse outcomes because they're not taking their medication. Either they're hitting access restrictions from insurance companies or they just can't afford or have problems with the cost sharing or something like that, and so trying to quantify how this is affecting patients. And so from a research perspective, I think that's kind of our next move.   My colleagues, my two neurologist colleagues, they're really active in kind of speaking with representatives at the state about the issue, bringing it to increased visibility from our elected officials as well as making sure that the MS Society is aware of kind of the current status of the pricing trajectory. So we've been updating our graph that we published as new agents come online and things like that.   MSDF Can you give us a couple of the updates you've made since the study?   Dr. Hartung They haven't been dramatic, but there's been a couple new agents that have been approved. And I guess most notably is that the first generic drug for MS was approved, I believe, last April. So a generic for Copaxone came online. I think there's two manufacturers of it. When it came online, there was one. And so I think it was priced just modestly lower than the brand name Copaxone. But something interesting also just dealing with Copaxone, which is the number one MS drug in terms of sales, so when Copaxone lost its patents and lost its kind of patent disputes, in preparation for that, Teva released a different formulation of Copaxone.   So Copaxone is traditionally a daily injection. And so they released a three-times-a-week higher strength injection and basically switched everyone from the once-a-day to the three-times-a week 40-mg injection. And so I think a large proportion of patients who were originally on the once-daily Copaxone were switched to the 40-mg three-times-a-week Copaxone. So that really to some extent mitigated if there's any sort of savings due to this new generics in the field, kind of really mitigated any kind of savings due to the new generic as most people are now on the 40-mg three-times-a-week product. And the generic is not substitutable for the 40-mg three-times-a-week product. So that's a very common tactic in pharmaceutical industry approach to try to like sustain their franchise with a particular drug that's going off patent.   But the big questions are the ones that don't have a good answer. Essentially, what do patients do about this? What do we do as a society to deal with this issue? And you know, there's been proposals that have been put out by different elected officials and other folks about, you know, we should allow Medicare to aggressively and directly negotiate with pharmaceutical industry on price. We should allow importation of medications from other countries, similar industrialized countries like Canada. So the United States pays by far and away the highest prices than any other country in the world. And so many people think that we should be able to import these drugs that are the same drugs that are going to Canada into the United States. You know, some people suggest that there should be some sort of forms of price control. You know, maybe medications shouldn't be allowed to increase 10% a year or something like that.   And so all of these are being kind of discussed and played out and the pros and cons are weighed. And whenever you talk about limiting price increases, the usual response you get from industry is that any constraint on the amount of money that they're able to make and the profits that they're able to make for their shareholders is going to have some sort of effect on kind of future innovation potentially. Whether that comes to bear or not is unclear, but that's usually the number one response you get is that we need to have these high profits in place because it's an incredibly risky endeavor that we're doing. Only a very small proportion of drugs that are under development actually make it through the developmental process and are approved and make it to market. So any constraint on profits is going to have an effect in terms of future innovations and future breakthrough medications and things like that. Incentives are a big…they are real. And so that is something that needs to be weighed carefully in kind of any solution, essentially. I don't think it's the best solution, but just people are talking about a wide variety of things, I think.   MSDF I appreciate your raising all these issues and going through the study. Is there anything else that I haven't asked that you wanted to add or emphasize as take-home lessons? Something to mitigate the rage, I don't know… [laughter]?   Dr. Hartung Yeah, well I mean there's been a lot with all this, you know, the Valeant Pharmaceutical issue and the other company, Martin Shkreli guy who's castigated for increasing the price of this drug for toxoplasmosis by like 5,000% and buying the company and jacking up the price. That's a separate phenomenon of what is happening. But I think the outrage over that type of exploitation of the dysfunctional pharmaceutical market kind of masks and kind of hides the other issues that are happening on a consistent and aggressive basis in terms of just regular 6% to 10% increases in price on a year-to-year basis for drugs that a lot of people use, like drugs for diabetes or MS products, cancer agents, things like that. And so, you know, you have these really highly visible cases of really dramatic increases that are kind of morally outrageous. They draw your attention from the real and kind of moderate but aggressive and year in, year out, increases that are seen across the board in a lot of different agents. And that's where our focus should be essentially.   MSDF That's helpful. Well, thank you so much.   Dr. Hartung Yeah. My pleasure.   [transition music]   MSDF Thank you for listening to Episode Ninety of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   [outro music]   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   For Multiple Sclerosis Discovery, I'm Dan Keller.

[intro music] Host – Dan Keller Hello, and welcome to Episode Eight-two of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. Depression affects as many as 50 percent of people with MS during their lifetimes. But according to Dr. Adam Kaplin, a psychiatrist in the Johns Hopkins MS Center in Baltimore, it is treatable to a large extent, and with good results. Dr. Kaplin studies the immune basis of depression and cognitive impairment, specifically in MS and central nervous system-related autoimmune diseases. We met in Baltimore. Interviewer – Dan Keller Let’s talk about depression in multiple sclerosis. Is it a reaction to someone having a chronic disease, or is there something more going on because of the disease? Interviewee – Adam Kaplin It’s a great question, and what I will tell you is one of my patients says to me that you’re either stressed, or you’re dead. We all have stress going on, and it’s always possible to look at something in our life and say, ah, that’s what caused the trouble. But we know now, in multiple sclerosis, the depression is due primarily and dramatically significantly to the inflammation going on in the brain that causes all of the symptoms that you see in MS, such as cognitive impairment, or weakness/numbness/tingling, autonomic nervous system dysfunction; all of those are effects of the MS on the CNS. And in the case of depression, it is similar. It’s not a character flaw. It’s not a personal weakness. And just to, you know, clarify, one of the best pieces of evidence we have for that is, number 1, that people who are depressed with MS, it does not correlate with their EDSS scores. It doesn’t correlate with their level of disabilities. So if it was you know, gee, it’s just a matter of stress, then those people who are in wheel chairs or on ventilators should be depressed, and those people who are upright and walking around shouldn’t. But in fact, I think the key element is that this is one of the, as they often say, silent symptoms of MS. It occurs to 50% of patients across their lifetime. And it is important you know for people to understand that this is not something that people aren’t rising to the occasion, or those kinds of things. MSDF Is depression accompanying MS more prevalent than in the general population, and how serious is it? Dr. Kaplin You know people often ask why, as a neuropsychiatrist, why study MS? And I say, you know, why did Willie Sutton rob banks? That’s where the money is. MS has the highest rate of clinical depression of any medical neurological or surgical disease. Again, 50% of people, following the diagnosis of MS, will have a clinical depression. We can talk about what that is. And it turns out that that’s in any clinic you go into – neurology clinic – that’s one in four patients. If you go out to the waiting room, one in four patients will be suffering from a clinical depression. MSDF How serious a problem is it? What aspects of life does it affect? Does it affect everything, and how serious is it? Dr. Kaplin I think what is often misunderstood about the depression in MS is, I would argue, that it has the highest morbidity and mortality of any of the symptoms of MS, in the sense that it is the third leading cause of death in the largest study that looked at, across the lifespan, what causes death in people with MS, [found] a study out of Canada, where it’s more prevalent because of the higher elevation and the lower vitamin D levels, probably. And it is absolutely the case that seven-and-a-half times the rate – the suicide rate in MS – to the general population. And in fact, in the studies that were done, 30% of people with multiple sclerosis will have thoughts of suicide at some point during their life. Ten percent – fully 10% will attempt suicide. And that lethality is profound. But if it doesn’t kill you, it is important to understand that it has significant, significant morbidity associated with it. Just to begin with, the number one correlate of quality of life of patients—more important than their pain, or more important than their cognitive impairment, or weakness, or other symptoms—the number one correlate of the quality of life of the patient is their depression or whether they are depressed or not. And it’s similarly the number one quality of life of the care givers—not whether they have to push them around in a wheelchair, it is whether their loved one is suffering from a clinical depression. So it has significant morbidity and mortality associated with it. MSDF Are there aspects of serious depression in MS that are very characteristic? Any different from other severe depression? Or can it be recognized in the same way with the same diagnostic criteria? Dr. Kaplin There actually are some specifics to MS, although that hasn’t been well-published. I can be clear about things that are well-supported by the literature, and then those that are my clinical experiences. What I can tell you is that the way we diagnose depression in MS is the same way we diagnose depression in people without MS, which is you have to have 5 of 9 symptoms greater than two weeks, one of which must be either decreased mood or decreased interest. And we remember it by SIG-EM-CAPS, the nine symptoms. Trouble with sleep, where people are often having early morning awakenings or hypersomnia where they just sleep all day. Loss of interest, people’s get up and go has gotten up and gone. Feelings of guilt or worthlessness – and that’s a big problem, because patients who are depressed as a result of that often won’t seek help. You have to ask about it. They won’t volunteer it. And loss of energy or fatigue; low mood – that’s the sadness part; concentration problem; appetite changes, either increased or decreased weight; and psychomotor retardation, they’re not their normal bubbly self; and thoughts of death or suicide. With MS, what I will tell you, I find that patients with MS often, rather than sadness, have very frequently irritability. That tends to be more common. And sleep is usually decreased, not increased, so I see very frequently increased early morning awakening and those kinds of things. One pearl, though, to keep in mind is – or two pearls – if you’re trying to make the diagnosis of depression in somebody with MS, the first thing to do, because there are overlapped symptoms like fatigue, like concentration problems between depression and MS, so there is frequently, in up to 80% of people, will have diurnal variations in their moods; so usually worst in the morning and better at night. Sometimes it’s reversed, but you know that person has the same life circumstance, the same disease circumstance in the evening that they did in the morning, but their mood has changed dramatically, often, with MS with these cyclical changes. And that’s a good indication that it’s not demoralization; it’s depression. The other thing is ask the loved one. Get an outside informant, because nobody gets the brunt of it quite like the family. And they know that person, and if the family member says the one thing I hear so often, this is not the person I married, then you’re pretty much on the right track if you’re thinking about depression. MSDF How amenable to treatment is depression in MS? Dr. Kaplin I think that that is probably one of the key aspects is to understand that it is very treatable. So my expectation when patients come to me and I diagnose them with depression is that I will get them a hundred percent well with respect to those SIG-EM-CAPS symptoms, back to their baseline. And it’s very hard to get patients a hundred percent well from their gait problems; a hundred percent well from their cognitive problems. And, again, what I tell people is, look, I can’t tell you whether your cognitive impairment is due to the depression or due to the MS, or maybe it’s 10% depression/90% MS or 90% depression/10% MS. But I can promise you this: treating the depression, the depression is much more amenable to treatment. We don’t have good treatments for cognitive impairment in MS to reverse the cognitive impairment, but boy, we can reverse it if it’s a symptom of depression. What’s really exciting now is that we are now understanding more and more that many of the treatments you use for depression end up being good nerve tonics. So, there was a double-blind placebo-controlled study of fluoxetine demonstrating that, in patients who weren’t depressed with MS, they had fewer gadolinium-enhancing lesions over 24 weeks. And then there was the FLAME study in a related kind of way looking at fluoxetine as a way of significantly enhancing the recovery of hemiplegic stroke patients. So it turns out that I wasn’t so misguided in thinking that studying the immune basis of depression would be important, because as it turns out, our treatments actually do have an effect on the nervous system and the immune system for general types of depression as well. MSDF That sort of covers the SSRI class. What about tricyclic antidepressants? What about SNRIs? Do those fit in? Dr. Kaplin Yes, so absolutely. So the topic of how to choose and select the right treatment for patients with MS is … we could spend an hour and just sort of get only the highlights done there. But generally there’re sort of two strategies. One is to use a medication that has the fewest side effects, so that you won’t have drug-drug interactions with the patient if they’re on a numerous medicines for other concerns—their other symptoms and syndromes—that the antidepressant won’t interfere with it. And so along those lines, escitalopram and sertraline have the fewest drug-drug interactions. You essentially don’t need to look up drug-drug interactions if your patient is on one of those two medicines. The other approach is to say let’s choose a medicine that will have favorability with respect to the side effects, will be beneficial for the problems that the patient has. So a classic example is duloxetine is FDA-approved, not just for depression, not just for anxiety, but also for neuropathic and musculoskeletal pain. So here you’re talking about one treatment that will help you with the fact that your patient, their depression will get better; their neuropathic pain will get better if they have migraines—which are often a comorbidity—that will also benefit the neuropathic pain from that as well. And you know you will get two birds with one stone, as it were. And then the tricyclics, as you had asked about, we’ve had a lot of experience with them. They also will benefit in terms of the urinary incontinence problem. They are strongly anticholinergic, and so you can also benefit in terms of preventing the urinary/bowel problems. So really Cymbalta as just sort of son-of-tricyclics, has some fewer side effects, but doesn’t, therefore, cover some of the things that the tricyclics will. MSDF As you alluded to earlier, the depression in MS may largely be a result of immune processes going on—inflammation, cytokines, things like that. So how well do the disease-modifying therapies of MS attack the depression? Dr. Kaplin You know you mentioned cytokines. So that is another way that we know that this is due to the inflammation—the depression in MS—and not just other things, because for instance, interferon-alpha used to treat patients with hepatitis C will cause depression in upwards of 20 to 25% of people who take it, not when they first start it, but within you know a week to two weeks after starting it, you know, then up to eight weeks. So that’s just one cytokine, and in MS, all of the cytokines get activated. And similarly, interferon-beta that’s used, or Copaxone, you know, the ABCR drugs that we’ve used to try to—you know, with great effect since 1993—to slow the exacerbations down in MS; they don’t stop the inflammation, they just alter it. And so not surprisingly, they do not have antidepressant properties. But when you look at something like Tysabri, we actually have not published this yet. We did present it at a MS conference but working in collaboration with Biogen. We are going to publish shortly data that shows that, in a double-blind placebo-controlled study of adding natalizumab to Avonex, or adding placebo to Avonex, those patients who were depressed to begin with show a dramatic and statistically significantly decrease in their depression as a result of the natalizumab. So natalizumab is actually quite a good antidepressant—we have data for it—because that really does shut the inflammation down in the brain, and since that’s causing the depression in MS, that’s what benefits them. MSDF Just to clarify, natalizumab is a good antidepressant in MS. Dr. Kaplin Exactly right. That’s exactly right. Although, you know, it’s good that you clarified that. What’s interesting is that now that people are beginning to appreciate the role of the immune system in idiopathic depression, people are beginning to say, hmm, maybe we should be looking at these anti-inflammatories and seeing if the anti-inflammatories benefit patients with depression. Now, nobody has tried natalizumab, but TNF-alpha inhibitors have actually been tried. There was a study out of Emory looking at using TNF-alpha inhibitors for refractory depression. And I think coming down the road there will be more and more studies that begin to show the role of anti-inflammatories for not all, but some people with refractory depression. MSDF Yes, I’ve seen some studies on anti-inflammatories—traditional ones, NSAIDS sort of things—presented a German study at a neurology conference. Didn’t do too much. Dr. Kaplin Yes. What I can tell you is that not all NSAIDs are created equal. Celecoxib actually now has five studies that are placebo-controlled that have shown its benefit for depression or bipolar disorder. And so when added to antidepressant by itself: No. But when added to fluoxetine or—I can’t remember what other; it might have been sertraline—it clearly had a statistically significant improvement in the depression response, celecoxib. But not all NSAIDs are created the same. MSDF What about non-drug therapies, cognitive behavioral therapy, even just physical activity? And, if someone’s depressed, isn’t it hard to get them up and do physical activity? Dr. Kaplin Well, I’m so glad brought that up, because I’d be remiss to forget that. So all of the data says, look, therapies like cognitive behavioral therapy are effective for mild and moderate depression. Antidepressants are effective as well. The data shows that the antidepressants work quicker, but that the combination of antidepressants and psychotherapy is much better than either one alone. So that’s a crucial issue. And to make sense of what has happened—and often when people are depressed, they’ve been depressed, and that’s caused damage to their professional life and personal life, and having someone help them sort of, depending how long the depression’s been going on, sort of talk them through, coach them through, how to get back up and going. However, in severe depression, you can talk till the cows come home. If your patient is so depressed that basically they have this tunnel vision, and all of the options that are in front of them, the kind of mental flexibility that you need for CBT to work, for instance, it will not work if you patient is really severely depressed. You have to get them started with the antidepressant, which really then serves as a catalyst for the psychotherapy to kick in. And then the aspect of exercise, you can’t really pick a topic related to MS where the answer isn’t exercise. Cognitive impairment, absolutely exercise is beneficial. Depression, exercise is beneficial. It stimulates growth hormones that have positive neurological effects on the CNS, as well as on the peripheral nervous system and body. What I tell people, again, is that if your patient is severely depressed, they’re not going just go back out and start running. So you’ve got to begin to have a plan where you say, look, we’re going to begin this medicine. As you start to be able to have the ability to you know maybe push yourself more than you might usually and just sort of walk down the block, and then you know walk for a mile and then start jogging for a mile and sort of build up to it, that’s very beneficial. MSDF Are there barriers to recognizing and/or treating depression both on the patient’s side and on the physician’s side? Dr. Kaplin The big barrier on the physician’s side is, you know, don’t ask, don’t tell. So if you don’t think of depression, or worse, if the neurologist says, well, I went into neurology not psychiatry, you know, this whole depression thing, that’s not my bailiwick, that’s not my responsibility, you’re missing the fact that this is —first of all, this is very rewarding. There’s nothing else that you could treat that gets a patient from being non-functional, sitting at home, not taking care of the family, not working, in a bed to fully functional, taking care of the family, back at work, like treating the depression can. But also it is. It affects all aspects. It affects the patient’s compliance with all your other medicines. It affects their ability to exercise, etc., etc. So, you know, you’ve got to think of it. And then you have to know something about treating it. One of the big problems with neurologists when they treat depression is that they don’t appreciate the fact that the goal is to get that patient a hundred percent well, because you sort of have this sigma curve where, if you get them 50% well, they’re still in that sort of steep portion of the curve where something comes along—an MS attack or you even a viral infection—and they will slip right down that curve. Whereas, if you can push them way out into the hundred percent well, that’s great. Now you can’t always do it with one medicine. You take the dose as high as the patient can tolerate, where the side effects don’t become worse than the depression you’re trying to treat. But then you might need to add another medicine, an augmenting agent or something, so you’ve got to make sure you recognize it and treat it. And then, what I always tell my colleagues—and my colleagues at Hopkins are wonderful; they do appreciate you know you’re treating the whole patient, not just you know their reflex arcs and that kind of stuff—and what they are very good at is, if the patient is depressed and suicidal, that is the psychiatric equivalent of a heart attack. So then they will get in touch with me and we’ll work together. So if you’ve got someone who’s suicidal, you really want to get in touch. Unless you have the utmost experience and confidence in treating the worst cases of depression, you probably want to get a psychiatrist involved, or mental health professional involved, to help coordinate the care for someone like them. MSDF Very good! I appreciate it. [transition music] MSDF Thank you for listening to Episode Eighty-two of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. [outro music] We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller.

Full transcript: [intro music] Host — Dan Keller Hello, and welcome to Episode Seventy-seven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. Pregnancy and the postpartum period present special concerns to women with MS. Dr. Annette Langer-Gould, a neurologist and epidemiologist at Kaiser Permanente in Los Angeles, investigates ways to lessen the risk of relapses in these women. We discussed the effects of breastfeeding, among other topics, when we met at the ECTRIMS meeting last fall in Barcelona. Interviewer – Dan Keller In terms of pregnancy and breastfeeding in MS, what are you looking at? Interviewee – Annette Langer-Gould We're studying modifiable risk factors for postpartum relapses in women with multiple sclerosis. And specifically, we are looking at starting therapy shortly after delivery, whether that can reduce the risk of postpartum relapses, whether breastfeeding, particularly breastfeeding exclusively, could reduce the risk of postpartum relapses, and whether vitamin D levels play any role in increasing or decreasing the risk of postpartum relapses. MSDF And are these women who are on disease-modifying therapy throughout pregnancy or not? Dr. Langer-Gould No. In our population, a little over 60% were treated prior to pregnancy. But we do have a decent number of women who had decided to never go on disease-modifying therapies before, and almost all of them stopped disease-modifying therapies either shortly before or when they find out that they're pregnant. MSDF In terms of each of those outcomes, what are you finding? Dr. Langer-Gould We haven't analyzed the data for the vitamin D yet, but in the German pregnancy registry, we just published the data in exclusive breastfeeding, and once again showed that exclusive breastfeeding does protect against postpartum relapses. In that population, actually 96% of the women had been on some sort of DMT prior to pregnancy, and none of them were treated throughout pregnancy. We also found that resuming DMTs does not seem to have a big effect on reducing the risk of relapses, particularly in the first six months postpartum. MSDF Is that in women who are exclusively breastfeeding or not? Dr. Langer-Gould Ah, so that's a good question. So there is no good safety data on taking the medications during breastfeeding. And therefore, many clinicians and most patients are concerned about potential theoretical risks. So behaviors are actually mutually exclusive. Women typically will either breastfeed or resume medications early in the postpartum course. The other thing we find in the Kaiser population is that there are still a fair number of women who neither breastfeed exclusively or resume their medications, which presents sort of an interesting opportunity. If we could show that one or the other behaviors is protective, perhaps we could encourage either exclusive breastfeeding or resuming DMT. MSDF If women are not breastfeeding, do you have an idea of the time course of resumption of risk for relapse? Dr. Langer-Gould Yes, so the concern about postpartum relapses really is about having a relapse in the first three to four months postpartum. If we look over at the whole pregnancy year, and that's about 30% to 40% of women. So this is actually still the best defined risk period for having a relapse and actually the only clear trigger—with perhaps the exception of upper respiratory tract infections—of relapses. So we know that having just had a baby or having an upper respiratory tract infection is a pretty strong predictor of having a relapse. So it presents sort of a unique opportunity to also look at other biological factors, like vitamin D, which is why we're interested in it, to see if any of these things have a strong role in relapses as well. MSDF If women are breastfeeding postpartum, what is the hormonal profile like? Is this almost like an extension of pregnancy? Dr. Langer-Gould For women who breastfeed exclusively, meaning that they breastfeed to the point of suppressing their ovaries and not resuming menstruation—so that essentially there's no regular meal that's being replaced by formula or by table food in the baby—they have very high prolactin levels. So it's actually a little bit different than being postmenopausal, in the sense that they have very high prolactin levels. And they have incredibly low nonpulsatile FSH and LH levels. In the postmenopausal period, there occurs a very high FSH and LH levels. The similarity, though, is that they both have bottomed-out estradiol and progesterone levels, in both women who are breastfeeding to the point of suppressing menses and also postmenopausal women. And of course the other similarity is that there's no ovulation occurring, either during pregnancy, during exclusive breastfeeding, or after menopause. MSDF So it sounds like breastfeeding is really a hypothalamic pituitary suppressant as opposed to in menopause, where you still have those cranking away, but just no response from the ovaries. Dr. Langer-Gould Correct. MSDF Can this be used in any clinical sense? Do you see an application? Dr. Langer-Gould The most obvious direct way to translate these findings is that that, if you have a woman with MS in front of you and she is pregnant and she tells you she'd like to breastfeed, we certainly have no good reason to discourage her. And that if anything, I would suggest that the data we've already published would point to the fact that we may want to encourage exclusive breastfeeding, provide them with lactation counseling, and also sort out exactly what the optimal duration of exclusive breastfeeding may be for these women. Is it really only eight weeks, which we had defined arbitrarily? Or does longer duration of exclusive breastfeeding have additional suppressive properties? And that would, of course, have implications in the United States for things like maternity leave and work accommodations to allow that to continue, if it has a strong therapeutic effect for the mother. MSDF What's the relapse rate among postmenopausal women compared to postpartum women? Dr. Langer-Gould So relapse rate declines with age. And so it typically in postmenopausal women, although there's not great data, we would expect them to have relapse rates of less than 0.3 per year, Annualized relapse rates of less than 0.3 per year. And in postpartum women, that first three to four months, the annualized relapse rate exceeds one. MSDF But men also have a decline in relapse rate as they age, too. So you can't attribute it to lower estradiol. Dr. Langer-Gould Exactly. Yeah, I think it's far more complicated than just a simple sex hormone effect. You know, that was sort of our first instinct from pregnancy or the reason pregnancy must be protective. It has to have something to do with estradiol or the very high progesterone levels. And that's what prompted the postpartum study and also the estradiol randomized control trial. And both of those, of course, disappointingly have been negative. In isolation, the sex hormones associated with the protective effect of pregnancy don't really have a protective effect on inflammation. It's probably more of a combination of factors that play into modulating the immune response. MSDF Where do you go from here? Dr. Langer-Gould I think that if we are able to reproduce the findings, looking at this population-based source, that early resumption of DMTs is not particularly helpful, but perhaps it may be later in the postpartum year, and that exclusive breastfeeding is, again, protective, then I think the next step really is to establish the safety of some of these medications during lactation. For several of them, there's really no biologically plausible reason to think that they would have an effect on the baby, as they're not likely to be absorbed through the gut or enter into the baby's bloodstream. Examples of that would be the large molecules like Copaxone, the interferons, and also the infusion medications, Tysabri (natalizumab), and rituximab as well. Although you may be able to detect them in breast milk, they are such large molecules that they would not diffuse across the baby's stomach and into the bloodstream. Think about it. If the mom has to take it as a pill, it is very likely to be transmitted to the baby. If the mom has to take it as an infusion or injection, very unlikely that oral route through the baby would have any effect. MSDF How sensitive is this effect to, as you said, exclusive breastfeeding? Can you start introducing formula, or it's all or none? Dr. Langer-Gould That's a really good question. So we did look at that also in the German pregnancy registry. So first of all, women tend to have very defined behavior. They tend to decide to supplemental feed with formula very, very early, before they've even established their full milk supply. So to back up even further, a healthy woman gives birth to her child. Usually menstruation will resume two months after delivery, not one month. So it does take the HPA gonadal axis a little chance to recover from those high-circulating hormones of pregnancy. And in women who introduce supplemental feedings, particularly early, we also see the very same thing; that they will resume their period at two months postpartum. Actually, most of the work done in this field has been done by nutritionists who are in developing countries who are interested in knowing what you should do if you see a starving mother and a starving baby. Who should you feed? It turns out that if you feed the baby, the mother's ovarian function will resume. So any regular supplemental feedings and very quickly their prolactin levels will drop. The pulsatility of the FSH and LH secretion will return. Ovulation returns, and so does menses. It's essentially sending the mother's body a signal that the baby no longer needs nutrition from the mom to survive, so she's ready to have another child. So the right thing to do in that situation would be feed the mom, and let her nurse the child. Biologically, it's very interesting. Even though some breastfeeding is better than none for the baby, in terms of the effect on the mother's HP [hypothalamic-pituitary] ovarian axis, some supplemental feeding is just like all supplemental feeding. MSDF Have we missed anything or anything interesting to add? Dr. Langer-Gould So I guess I would say just in general, women's, and now even men's, desire to have naturally-born children has taken on a new significance with a lot of the small molecule agents, because we need to consider family planning and discuss it much earlier, as small molecules are likely to have an effect even if they get pregnant accidentally on the developing fetus. This is a challenge we haven't had before, because large molecules won't cross the placenta in the first trimester. And the first trimester is the critical period for organ development. So it's sort of new era for MS neurologists, where we really, really have to think carefully about which medication we put them on if they're planning on having children soon. So I’d strongly encourage that you have that conversation very early and have it with every followup visit. I typically will ask them, are you planning on having children within the next two years? And if they say, no, I ask what kind of birth control they're on, or in some cases they're in same-sex couples. That's obviously an exception. And if they are not on a reliable form of birth control, I think you need to think twice about giving the small-molecule agents—so the pills, basically. MSDF Should MS neurologists work with high-risk OB/GYNs? Dr. Langer-Gould I think for the most part it's not necessary, because women with MS, they don't have abnormal complications at pregnancy. I think there are certainly situations that we're running into now. If they get pregnant accidentally on fingolimod, teriflunomide, or Tysabri, we do need to work with them, mostly for the baby. So you may want to do more intense early screening if the mother is culturally open to the idea of having an abortion. You may want to do more fetal ultrasounds, perhaps even a fetal MRI, if there's suspicion of major malformations early on in pregnancy. And also for the Tysabri, really, it's not so much about organogenesis, but if they've had later exposure to Tysabri during pregnancy, which unfortunately on occasion has been necessary to control rebound disease activity during pregnancy, that, you know, we have seen hematological abnormalities in some of these children, so far none with clinical complications. Only one child had a subclinical intraventricular hemorrhage that resolved. It's still concerning. Our experience is very small, and we would certainly highly recommend that those women give birth in a hospital that has a neonatal intensive care unit available and a pediatrician on call to examine the child and also make sure that the child doesn't have a severe thrombocytopenia or anemia at birth. MSDF Do the different drugs have different risks for fetal malformations or other dysfunctions? Dr. Langer-Gould Yes. So teriflunomide, or Aubagio, is the most concerning medication because if a woman gets pregnant on that accidentally, it is, you know, a category X drug because it can interfere with neural tube development. And although you can chelate to get the medication out very quickly, the safety data from other indications, you know, the rheumatoid arthritis and lupus literature, is not particularly reassuring in terms of fetal outcomes. So I think that's sort of the number one to stay away from if a woman is planning on getting pregnant. And it's also one where, you know, there is some concern, although not strong evidence, that it may also affect the offspring of men with MS who are on the medication. In terms of the other ones, of course, again, small molecules in fingolimod has about a 15% to 16% major fetal malformation risk with early pregnancy exposure. It has a very long half-life. So even if they stop the medicine the minute they find out they're pregnant, it takes over two months for it to be cleared, which means that the baby has seen it now through the entire first trimester. That can have significant effects, both on cardiac and brain development. And then with dimethyl fumarate, we haven't seen—now of course, this is a very new drug, so we don't have nearly as much experience—we have not seen any major malformations, but there was concern in the animal models that it could interfere with cognitive development. In particular, the rats had maze-finding difficulty. MSDF Is alemtuzumab indicated at all? It seems to have a long tail. Dr. Langer-Gould I'm not sure what the half-life of alemtuzumab, but it's probably similar to other monoclonal antibodies, which is usually around 15 to 20 days. So monoclonal antibodies don't cross the placenta in the first trimester, because it's a very large molecule. So large molecules only get across if there's an active transport system. For antibodies, there is an active transport system, because it's very important that the child be born with a high dose of antibodies received from the mother to help protect them during the early part of their infancy while their own immune system is still developing. So we see maternal antibodies being transported, and of course, monoclonal antibody medications would be dragged along with that during second trimester. And it goes up in elliptical fashion, with very, very high amounts being pumped across the placenta in third trimester. And they also, of course, have a very delayed clearance mechanism, both the fetus really has no clearance mechanism, and then even the neonate has a very slow clearance mechanism. So in TNF alpha studies, if the drug is given during third trimester, it's typically not cleared until about six to nine months postpartum. So you also have to be concerned that a baby exposed would have some of that medication hanging around during the early neonatal period and give some thought to whether or not their immunization scheme would need to be adjusted, as the cautionary tale there would be TNF alpha exposure during pregnancy. There was a case reported of a woman who had very severe rheumatological disease, had discussed with her rheumatologist the potential risks and benefits of taking it throughout pregnancy, opted to take it throughout pregnancy. And then living in an endemic area for tuberculosis, the baby got the BCG vaccine and got disseminated mycobacterium and died. And that, you know, was probably directly related to impaired immunity from the TNF alpha antagonist. And sure enough, the baby was born with fairly high cord levels and also had very high levels still remaining in the blood in the neonatal period. So it's not just once the baby's born, it's like the drug is out. So drugs like alemtuzumab and rituximab, the way in which they work, even though the drug could be long gone, but the effect of the medication works very long time. So those are actually good choices for women with highly active disease who are planning on getting pregnant. And you have concerns about rebound. I mean, we typically use rituximab because it's obviously much safer than alemtuzumab and seems to do a fairly good job. But you know, these aren't medications we should be giving while they're pregnant, but probably not a big effect in crossing the placenta and on the baby if they're used prior to pregnancy. MSDF If they can plan that well and get a pulse of that early, and then get pregnant a few months later. Dr. Langer-Gould Yes. Yeah, that's always the trick, right? And they do get pregnant accidentally on just about everything we put them on. So the infrequent infusion medications is the easiest because you can ask about last menstrual period. And you can ask about birth control use, and you can do a pregnancy test the day of, a quick urine dipstick and find out so that you don't accidentally infuse a pregnant woman. Of course with Tysabri, when you're giving them an infusion every month, it gets a little tricky. Usually people just kind of get tired of it. The nurses forget. The doctor forgets to order it, although it's not necessarily bad practice if you know you have a patient who is not on a reliable form of birth control. MSDF Very good. I appreciate it. Thank you. Dr. Langer-Gould You're welcome. [transition music] MSDF Thank you for listening to Episode Seventy-seven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. [outro music] We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller.  

Who has heard of the MS hug? Have you ever heard of Tysabri the drug that stops episodes? Well, Mary Burke has and she joined us to talk about MS in Liverpool. #MS #Multiplesclerosis #Liverpool #MSfamily

[intro music]   Host – Dan Keller Hello, and welcome to Episode Forty-nine of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features Dr. Hugh Rosen of the Scripps Research Institute. But first here are some new items in the MS Discovery Forum.   If you’re an MS researcher, you may want to keep an eye on our Bulletin Board section, where we post a variety of news items that may be of interest. One of the items we posted this week is directly related to Dr. Rosen’s work. It’s a notice that a phase 3 trial of a sphingosine 1-phosphate receptor modulator called RPC1063 has started recruiting twelve hundred patients with relapsing remitting MS in the US. RPC1063 had its origins in Dr. Rosen’s lab.   We also recently added a notice of another clinical trial to the Bulletin Board. That one’s a phase 2 trial of oral laquinimod in primary progressive MS. And a third new Bulletin Board announcement is a request for information from the Patient Centered Outcomes Research Institute to identify patient registries and research groups with established cohorts of patients for potential collaborative research opportunities on comparative effectiveness research in MS treatment.   To read any of these announcements, go to msdiscovery.org and click first on Professional Resources and then on Bulletin Board. And if you have an announcement you think may be of interest to MS researchers, please send it to editor@msdiscovery.org. We won’t post purely promotional press releases, but if we judge the notice to be of general interest, we’ll be happy to post it at no charge.   In other news, it was a relatively slow week in published MS research. According to our curated list of the latest scientific articles related to MS, only 22 such articles were published last week. Typically at least 40 MS-related peer-reviewed articles are published weekly, and we’ve seen some weeks with more than a hundred. To see the weekly lists going back to March 2012, go to msdiscovery.org and click on Papers.   Our Drug-Development Pipeline includes continually updated information on 44 investigational agents for MS. This past week we added 2 new trials and 7 other pieces of information. The drugs with important additions are dalfampridine, fingolimod, masitinib, and natalizumab. To find information on all 44 compounds, visit msdiscovery.org and click first on Research Resources and then on Drug-Development Pipeline   [transition music]   Now to the interview. Dr. Hugh Rosen studies chemical and biological approaches to the molecular mechanisms regulating lymphocyte trafficking. I met with him in his office at the Scripps Research Institute in La Jolla, California.   Interviewer – Dan Keller We're talking about mostly new compounds, S1P1 receptor compounds; the prototype now I suppose is fingolimod. What's in development and do they appear to offer advantages?   Interviewee – Hugh Rosen So, firstly, let me disclose that I am a cofounder of a biotechnology company called Receptos that has licensed an S1PR1 agonist from the Scripps Research Institute, so I have and my institution have a significant interest in this particular field.   Sphingosine 1-phosphate receptors act in a number of ways to modulate immune tissue damages in both autoimmune diseases and in viral infections. They've proven to be particularly efficacious in multiple sclerosis. Gilenya, of course discovered by Yoshitomi in Japan and developed by Novartis, has proven to be a clinically useful compound in the treatment of relapsing-remitting multiple sclerosis. And it appears to do so, at least in part, by altering the ability of lymphocytes to recirculate, and thus lymphocytes to reach the target tissues where they, in fact, produce demyelinating damage to the white matter of the central nervous system, and then the signs and symptoms of multiple sclerosis. So clearly these are useful compounds.   Gilenya, of course, is not a selective small molecule, it is an agonist of four of the five high affinity receptors for sphingosine 1-phosphate – S1P1, 3, 4, and 5 – and some of the associated side effects may be attributable in part to activity of Gilenya on other receptors like the S1P3 receptor that are not required for modulation in the treatment of multiple sclerosis.   MSDF I see that it's referred to as an immunomodulator, not necessarily referred to as a receptor agonist. Does it not have pure agonist effect? Does it have any effects either because of the other receptors or at that same S1P1 receptor?   Dr. Rosen No. In fact, Gilenya when phosphorylated is a full agonist of the sphingosine 1-phosphate receptors, and the newer compounds that are much more selective are also agonists of the sphingosine 1-phosphate 1 receptor. And some of the effects on them for cyto-mediated by downmodulation of the receptor, but I don't use the term modulators or immunomodulators because of the activity on the sphingolipid receptors per se, I use the term immunomodulator because of some of the unique advantages that we've demonstrated in model systems and in man about altering the activity of the sphingosine 1 receptor, because one of the beauties of immunomodulation is to blunt the immune response that causes collateral damage to the tissues whilst leaving sufficient of the immune response intact to allow protection from opportunistic pathogens – bacteria, viruses, and yeasts.   So one of the most striking features that we found – and these have been in some experiments done as a collaboration between my laboratory and the laboratory of Professor Michael Oldstone here at Scripps – has been in the area of influenza; pandemic influenza causes significant collateral tissue damage by having an overactive immune response. What we show is that the sphingosine 1-phosphate 1 receptor blunts that immune response and blunts the amplification of cytokines and chemokines so that you protect from the collateral tissue damage, but you leave intact the ability to mount protective, sterilizing T cell and B cell immunity to the virus. So you can eradicate the virus, sterilize it, you can provide a long-term memory both on the T-lymphocyte side as well as on the antibody side; there's class switching, there's affinity maturation, there are good protective immunity that is produced, and all this while blunting the immune response.   This is the Holy Grail as we think about treating patients, because the window for patients with autoimmune diseases like multiple sclerosis is that window between effective blunting of the immune response and the prevention of deleterious opportunistic infections that can have life-threatening consequences. So one of the advantages that I suspect we will see over time is that the sphingosine 1-phosphate agonists will prove to be particularly well-tolerated and have a wide window between the ability to limit tissue damage and progression of RRMS, and the need to protect patients from intercurrent infections or subclinical infections that become expressed later.   MSDF Do the other sphingosine 1-phosphate receptors interfere with lymphocyte trafficking also, or do they have other effects which nonselective ligands would then induce these adverse effects through them, or do they also have some effect in terms of trafficking?   Dr. Rosen They don't have significant effects on lymphocyte trafficking the way that S1PR1 does, both from the chemical approaches and the genetic evidence. S1P1 is clearly a toggle switch for lymphocyte trafficking. S1P2 is involved in the maintenance of hearing and in the function of vascular smooth muscle, so it regulates blood pressure. S1P3 is involved in cardiac contractility and also in the control of coronary artery caliber and the control of the airways, so S1P3 agonism is not a useful thing, it's actually quite deleterious. S1P4 and 5 have really no rate-limiting functions, at least of which I am aware, so there may be some redundancy and may not play a critical role in the modulation of health and disease.   MSDF Do you see compounds coming along which will be more selective and therefore not lead to the adverse effects so much? And if so, are these compounds chemically similar or do they have different structures to attach to the receptor, the S1P1?   Dr. Rosen These are clearly different structures, they're structurally very distinct from Gilenya and from each other. Novartis have a backup called siponimod. Actelion had a compound but it's only being used in psoriasis called ponesimod. Receptos has a compound now known as ozanimod – formerly known as RPC1063 – that is in two phase 3 studies for relapsing-remitting multiple sclerosis, a two-year study called RADIANCE and a one-year study called SUNBEAM, both of which are enrolling twelve hundred patients each.   MSDF And the RADIANCE trial results looked pretty good; I mean, you had 85, 90% effects at 12 to 24 weeks or even at a year in terms of relapse rate. Does this look like the next compound to emerge?   Dr. Rosen I think it's likely that ozanimod will be the next compound to be submitted for the regulatory process here in the United States and probably in Europe as well. The pleasing thing about the phase 2 data for ozanimod was, in fact, both the strong efficacy signal and a very well-tolerated safety profile; in fact the adverse effect profile of ozanimod and placebo were, in fact, indistinguishable and overlapping in the phase 2 studies. In addition, this very well-tolerated, favorable safety profile has been replicated in a highly successful phase 2 study in ulcerative colitis called TOUCHSTONE that was released recently. So clearly this is a mechanism of immunomodulation that could well prove to be useful for relapsing-remitting multiple sclerosis, but also in a range of other autoimmune diseases where treatments are hard to come by.   MSDF Even with Gilenya, I think there have been reports of a couple of cases of progressive multifocal leukoencephalopathy, so it gives a nice balance between immune surveillance and inhibiting T cell trafficking, but it seems like not a perfect balance. Does it look like that margin will be narrowed in the future with other compounds?   Dr. Rosen It's possible that it will be. I think the critical point to bear in mind is that real-world experience in tens of thousands of patients with hundreds of thousands of patient-years is really ultimately what is required to define these very rare events that on occasions do occur, and preexisting treatments with other immune-modifying agents such as Tysabri, for instance, may predispose to issues being seen later with PML. And I think that we always have to say that long-term patient experience and physician comfort are ultimately the best guides to the risk-benefit ratio.   MSDF I think you've identified something like four compounds in development, those are some that I had seen. Are there others, or these are really the ones to focus on at this point for people to keep an eye on?   Dr. Rosen There may well be others that are further behind. There have been a number of others that have had safety signals, particularly liver enzyme elevations, and significant first-dose cardiac effects. Arena have a compound that has recently completed a phase 1 multiple-dosing study and will go on to phase 2. So, you know, there are additional compounds and there will be additional compounds. Ultimately, patients do best when the best compounds appear, and the only way one knows that is to test them in man over the long-haul and define that risk-benefits for patients. And, you know, these multiple efforts really reflect the fact that a field has advanced, and that advancing field really does improve through intelligent intervention our ability to offer patients a better set of choices and a better set of long-term outcomes, which is what we're all about.   MSDF We're still focusing here on RRMS, none of this applies to the progressive phase. Is there anything coming along there?   Dr. Rosen You know, there's been one trial in primary-progressive; this was the Gilenya trial which didn't meet its endpoints. It may be that the mechanisms in rapidly progressive MS are a little different and that we don't yet, I think, understand the pathogenesis of that rather different presentation. So I'm not aware of a good alternate approaches to that, but that doesn't mean that the understanding isn't there for that to happen over time, it simply means that I'm not yet aware of it.   MSDF Finally, in secondary-progressive MS, we can understand what's going on, what led to it; if you limit relapses, that's good. But does it look like primary and secondary really may be overlapping but not the same disease?   Dr. Rosen I think there may be balances of pathogenesis where you can intervene more easily in some than in others. Clearly the sphingosine 1-phosphate agonists work particularly well by inhibiting the movement of lymphocytes into the brain. The movement of lymphocytes from the perivascular cuff into the parenchyma, into the white matter, where the demyelination proceeds. However, in parallel in multiple sclerosis, there are also events where there is collateral damage to neurons; we see axonal severing, we see elements of neuronal loss. Certainly with the sphingosine 1-phosphate agonists, there is some evidence that there is a diminution of cortical thinning over time with treatment, and that may be a really good thing.   I think that the neurodegenerative components is one that is hard to get a handle on right now, and that I think that these differences will become more obvious with early treatments of the immunopathology of multiple sclerosis. And that may well separate the autoimmune inflammatory damage and its sequelae from neurodegenerative mechanisms that may be entrained, and I think we will learn a lot from looking at those subsets of patients over time, particularly as more, better, and earlier treatment modalities allow the avoidance of significant damage in most patients.   MSDF Is there anything important we've missed or you'd like to add?   Dr. Rosen You know, I think for all of us who try to work at this interface of therapeutics, we do so because disease is, in fact, personal. We all know patients, we've all seen the multigenerational impact and depredations of multiple sclerosis on friends and family. And I think this is the very strong underlying motivator that drives us as scientists and as physician scientists to really try and bear in mind that the basic mechanisms and the basic therapeutic approaches that we pursue ultimately need a safe and effective human face to change the lives of patients in a positive way.   MSDF Very good. Thank you.   [transition music]   Thank you for listening to Episode Forty-nine of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]

[intro music]   Hello, and welcome to Episode Forty-Three of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. May Han, who discusses issues related to following patients with clinically isolated syndrome. But first, here are some new items on the MS Discovery Forum.   We recently posted an article on a surprisingly strong association between a certain gene variant and non-response to interferon beta in people with RRMS. The study is a meta-analysis of three independent cohorts in Italy, France, and the U.S., and it comes from the labs of Philip De Jager and Filippo Boneschi. You’ll find this article by clicking first on News & Future Directions and then on New Findings.   This past week we published the latest in our series of data visualizations. This month’s visualization is a series of word clouds illustrating how key terms in the MS clinical-trial literature have changed between 1993 and 2014. To find this visualization, first click on Research Resources, then on Data Visualizations, and then on Word Cloud.   According to our curated list of the latest scientific articles related to MS, 30 such articles were published last week. To see last week’s list, go to msdiscovery.org and click on Papers. We selected one of those papers as an Editors’ Pick. It’s study of the association between depressive symptoms and walking ability in people with RRMS.   Are you attending the annual meeting of the Consortium of Multiple Sclerosis Centers in Indianapolis this week? If so, please come visit us at the Accelerated Cure Project’s booth. We’ll be demonstrating some of our latest data visualizations along with other features of the MS Discovery Forum. You’ll find the booth in the hallway close to the main entrance to the exhibit hall, and we look forward to meeting you.   [transition music]   Now to the interview. Dr. May Han is an assistant professor in Neurology and Neurological Sciences at Stanford University. I spoke with her about following patients with clinically isolated syndrome, as well as her approach to patients with MS across the course of their disease. But first, she addressed some unmet needs in MS.   Interviewer – Dan Keller Dr. Han, you told me that we’re good at the diagnosis of MS in general, but still there’s a vast area that we don’t know about. What are some of those unmet needs?   Interviewee – May Han So it’s been over 150 years since Charcot first described multiple sclerosis, and I have to say that we have come a long way in understanding and treating this disease. But as you have mentioned, there are still areas where we have no idea, there are gaps in our understanding of this disease. One of these areas that is clinically very relevant and is very challenging is in the day and age where we have a dozen disease-modifying therapies for MS patients, and yet we don’t have a good way, a scientific way of selecting the most effective therapy for a particular patient is what I find quite challenging in the clinics.   MSDF What gives you clues or how do you approach this essentially algorithm of deciding where to begin and how to move on to other medications if the first one’s not working well?   Dr. Han Currently, of course, we follow the guidelines. So for any relapsing-remitting patients, our logic is to go for the safest medication that we think are going to be most effective, which means we go with the first-line therapies. So we have the convention ABC drugs such as beta-interferon family of therapies and glatiramer acetate, plus the newer oral medications such as Tecfidera and fingolimod or Gilenya that we use for the first-line therapy; not a whole lot of science in choosing these medications for a particular patient, but what we would do is initially we would educate the patient about these disease-modifying therapies and then select the medication together with the patient to see what would be most appropriate and the patient could be most compliant for a particular medication.   To give you an example, certain patients have aversion to needles, in which case we go with the oral medications. We also have in mind what the preference of the patient, such as whether they could be able to follow it through for years on end with a particular medication. Ideally, we would like to have zero relapses or MRI activity when a patient is on a disease-modifying therapy, but as we all know none of these medications are 100% foolproof, and they can still have some degree of MRI activity or infrequent relapses on this medication. However, if a patient is clearly not responding to a therapy either in terms of not being compliant, being intolerant to the mode of administration, or if they’re having worsening disease activity, we would decide to go on to stronger medications or second-line of therapy.   MSDF Do you initially discuss a plan of action, a stepwise pattern of medication prescribing, or do you wait until something needs to be changed to bring it up with patients?   Dr. Han That is a very good question. I’m sure it varies among clinicians, but, however, I would like to paint the picture to the patient the best that I can. So, let’s say for example, if a patient who is a newly-diagnosed MS patient who has very few MRI lesions, I would discuss with them what the most appropriate medication could be. We would decide a medication and we would also give them an outline of what the followup plan would be and when we would be deciding to switch to a different therapy, and if so, which medications would be most likely appropriate for them, and also how we would monitor them. So by doing this, it gives the patient a better picture of their path and what to watch out for, and in my experience we have a better outcome with these patients.   MSDF Do you find that once you achieve success in limiting relapses and lesions that the medication is fairly stable for a long time, or do you have to have an armamentarium that you keep moving through?   Dr. Han So my model if a patient is responding to a medication, unless they have other side effects or reasons to switch, I would like to get the most mileage out of the medication as much as I can for a particular patient. However, if a patient, for example, has JC virus positivity, in which case even if they’re responding to Tysabri really well, there is a cutoff time point where we have to sit down and consider whether this patient should be switched onto a different medication to prevent the development of opportunistic brain inflammation such as PML, in which case what the next medication would be. And so we would sit down and talk the pros and cons; this conversation was started even before the patient was started on medication, but that would be the checkpoint.   MSDF I suppose another aspect is do medications start to fail patients even after a long period of stability, or do they usually continue to be stable if the medication is working for some period of time?   Dr. Han This is also a very pertinent question. MS patients, as we know, is very heterogeneous. Some of the patients, if they are stable on a medication, they would continue to do well on a medication for several years up to decades. However, some patients would have an initial improvement or stabilization of their disease, however in the later stages they would have worsening disease. And it is really unclear whether because their disease per se is getting worse or whether their body is rejecting the medication secondary to the immune response. And that is also one area that we should do research on to better understand this condition.   MSDF When you say reject the medication, are you actually referring to an immune rejection such as with, say, interferon; I would think it would be less likely they would actually mount an immune response to a small molecule. Am I clear on that or not?   Dr. Han I think we have quite a lot of information in terms of beta interferon therapies, because we clearly know that patients do tend to develop antibodies against beta interferon, especially the therapy. However, even that we don’t really know if all those antibodies are attacking the drug or whether they are just there. So just by finding the antibody alone is not enough to say that the patient is not responding to it; I think we need to use it hand-in-hand with the clinical response as well as the MRI activity.   Getting to the second part of your question whether there’ll be less intolerance or rejection to the therapy if it were small molecules, but I don’t think we understand at the cellular or molecular level. For small molecules there could be receptor down-regulation, there could be availability or cellular sequestration, or even the prodrug being converted to an active drug, or how the breakdown process occurs. So when a patient does not respond anymore to a medication, we just know that the clinical response is worse, and we don’t really know whether it is because the disease activity has worsened or other aspects, pharmacodynamic or kinetic aspects of the system has changed in such a way that they no longer respond. So, again, we do need to do more research to have a better understanding.   MSDF You have called it MS comes in many different flavors. Have you found that any medications are particularly good for different constellations of symptoms, or is everything about equal no matter how they present?   Dr. Han Very good question as well. I think in the experimental models people know that MS, or central system autoimmunity, can have a bias towards one type of inflammation as opposed to the other. For example, some would say that certain medications are better to treat Th1 as opposed to the Th17 type of inflammation, however in human beings there’s no clear-cut Th1 MS or Th17 MS. I don’t think people have done enough studies to clearly decipher the immune profiles of patients. So the answer is we don’t know.   MSDF Finally, let’s talk about the need for biomarkers especially very early in the disease when someone’s presenting with CIS which may or may not become MS. Where does that stand and how acute is the need?   Dr. Han The need is there, especially if you look at it from a patient who just had an initial attack. If you tell them that we don’t really know whether this is a one-time thing or whether you’re going to develop MS, and we’ll have to wait and see for three-plus years. So for these three years, the patient’s life is very much consumed by the “is it going to be MS” kind of question. And it does affect their physical-mental wellbeing as well as their quality of life.   I think we’ve come a long way with the advancement of the MRI studies in such a way that if a patient has MRI lesions together with the first-time attack, we could almost clearly say that this is going to blossom into MS. However, for patients who are radiographically clean and who just had one episode, it would be very, very helpful to have some kind of blood biomarkers to predict whether this could be a single event or whether it could be a central nervous system inflammatory disorder.   MSDF You picked three years as a period of waiting, watching. Are they out of the woods after that, or how late can it blossom into full MS?   Dr. Han It’s always a bell-shaped curve. There are patients who would declare themselves sooner than three years, there are also patients who would take several years before they have the second attack. I have one patient who had an initial attack of optic neuritis and nine years later she had the second attack. During that period, she had had MRI scans for three years which were clean. So, I guess, one is never completely out of the woods, but at the same time it is also not prudent to perform unnecessary tests on a patient.   So I think we have to focus on what is the safety net and pick a period of time, but at the same time it is very important to educate a patient to symptoms to watch out for, how to get help, and to work very closely with the primary care physician or a neurologist so in case the symptoms show up they will not be ignored or delayed to receiving treatment.   MSDF Is there anything we’ve missed or is important to add? I’m sure it’s a gigantic field, but is there anything glaring that should be added?   Dr. Han I would like to encourage people in the field to also focus on the secondary-progressive stage of MS. We know that relapsing-remitting MS patients with or without therapy eventually would end up having secondary-progressive MS, so it’ll be really important to decipher whether during the secondary-progressive stage there is no inflammation but only the early neurodegeneration, or how the immune system and the central nervous system interact and how we can change it, or at least modulate it, to either delay or to prevent neurodegeneration. The third area that I think is very important is to try to understand the regenerative aspects of the central nervous system.   As I have given you the example, if we have two patients who have had similar lesion burden or even lesions that are approximately the same in similar areas, a patient can be severely devastated, neurologically devastated, whereas the other may have minimal neurologic deficits. And we would always say that it depends on the brain reserve, or neural reserve, but we don’t quite know what it is. Is it the stem cells, is it the nervous system being more resistant to insult and how the immune system interacts with it? And I think this is also a big area that we should focus on, of course, to prevent further damage, but also once the damage is done to limit the damage and perhaps to regenerate it. And I think that people always have within themselves the ability to heal.   MSDF Good, thank you.   Dr. Han Thank you.   [transition music]   Thank you for listening to Episode Forty-Three of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]

[intro music]   Hello, and welcome to Episode Thirty-Eight of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features part one of a two-part interview with Joseph Berger of the University of Pennsylvania. But to begin, we’d like to tell you about MSDF’s Drug-Development Pipeline.   Twelve drugs are currently approved in the US for the treatment of MS, but there are many more drugs in various stages of clinical and pre-clinical development. We’re keeping daily track of 44 of them in our Drug Development Pipeline.   To visit the pipeline just go to msdiscovery.org and click on Research Resources, and then Drug-Development Pipeline. You’ll find a finely detailed, fully referenced, and easily searchable database of all 44 of those drugs. The database includes details on each drug candidate’s physiology, its progress through pre-clinical and clinical trials, and its regulatory and commercial status.   Science journalist Heather McDonald has managed this database since its inception, and she updates it continuously, whenever new information becomes available. In just the last week, for example, she added one new clinical trial to the database, she updated information on two other clinical trials, and she added 5 other pieces of information. The drugs with important additions and changes were dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b, mitoxantrone, natalizumab, and RPC1063.   [transition music]   Now to the interview. Dr. Joseph P Berger is a professor of neurology and Chief of the MS Division at the University of Pennsylvania in Philadelphia. In part one of our discussion with Dr. Berger, we’re talking about the risk of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that occasionally arises in people being treated for multiple sclerosis.   Interviewer – Dan Keller The topic of quantifying risk and mitigating risk comes up with certain immunosuppressive drugs, notably natalizumab in MS but also with other drugs as well in other conditions. What are some of the confounding factors? Why is this not an easy thing to approach?   Interviewee – Joseph Berger Well, it’s not easy because it’s so unpredictable. Nobody would have thought that natalizumab would have uniquely predisposed to the development of progressive multifocal leukoencephalopathy. In fact, when natalizumab was introduced, if one would have attempted to predict what would have happened, you might have said, well, we’ll see a wide variety of opportunistic infections of the central nervous system, since this is a drug that prevents the neural immunosurveillance that is necessary to prevent these diseases from occurring. However, that’s not what we see. We don’t see the opportunistic infections of the central nervous system that we see in the AIDS patient; for instance, things like cryptococcal meningitis and toxoplasma and tuberculous meningitis, it simply doesn’t happen. What we see, on the other hand, is this unique increased risk for the development of progressive multifocal leukoencephalopathy. This was an entirely, in my mind, unpredictable event. I suspect that this is true of many of the other drugs that are now coming to market; that our experience with them is limited, they have what we think is a well-defined effect on the immune system – they’re not broadly immunosuppressant – yet our knowledge of the immune system is such that we don’t understand fully the downstream effects they have. And it’s only after we’ve used these drugs for a number of years do we have a comfort level with what sort of risks that are engendered by their use.   MSDF But it’s not unique to natalizumab; other drugs can induce this whether in neurologic conditions or even rheumatologic conditions. Is that right?   Dr. Berger Yes. In talking about PML, that is true that there are other drugs that carry black box warnings for the development of PML; however, there’s something unique about natalizumab and another drug that is somewhat related to it and now off the market called efalizumab, which was a drug which went by the name of Raptiva and was used for the treatment of psoriasis. So there are drugs that uniquely increase the risk of PML and there are those that marginally increase the risk of PML, and one shouldn’t conflate them. And though a drug carries a black box warning for PML, it doesn’t necessarily mean that the risk is the same as it is with another drug that may also carry such a warning.   And let me explain this a little further. If you look at natalizumab and you look at efalizumab, those are drugs that have been used for conditions that had never previously been associated with progressive multifocal leukoencephalopathy. So despite the fact… And natalizumab, as you know, is used in the treatment of MS and used in the treatment of inflammatory bowel disorders, in particular Crohn’s disease, efalizumab used in the treatment of psoriasis; these are autoimmune diseases. And prior to the availability of these compounds, we did some aggressive immunosuppressive therapies in the treatment of these diseases. We would treat them with drugs like Cytoxan and azathioprine and high-dose steroids; a wide variety of things were employed. Yet until the PML experience with natalizumab and efalizumab, we had never seen PML in the setting of multiple sclerosis, in the setting of inflammatory bowel disease, or in the setting of psoriasis. So that tells you that there’s something unique about the drugs that we’re using and that it’s not necessarily the underlying condition that is responsible.   The second is when you start the drug, you do not see PML develop immediately; it takes some time. So the experience with efalizumab was three or more years, the experience with natalizumab is typically 12 months; actually the vast majority of cases – over 80% - have been on natalizumab for 24 months, so they’re on the drug for a long time. The shortest latency from initiation to the development of PML has been a single case in which it developed within eight months; everything else is 12 or more months. So what is that telling you? That tells you that the drug is doing something fundamentally to overcome the barriers to the development of this disease and that it’s not simply opening up a gate and letting the horses out; it’s doing something to the pathobiology of the disease.   And then lastly, the incidence with which we see PML with natalizumab – and presumably with efalizumab, although the numbers were much smaller – is extraordinarily high in the appropriate context. So for natalizumab, the risk of developing PML, provided you’re on the drug for two years, you’ve seen prior immunosuppressive therapy, and you’re JC virus antibody-positive so that you have been exposed to the virus that causes this disease, if you have all three of those, your risk is on the order of 1 in 90 or thereabouts. That is a risk that is commensurate with what we see with HIV-associated PML, so it’s very, very high.   However, if one looks at these other drugs which I have called Class 2 agents in several papers now; drugs like rituximab, also a monoclonal antibody though directed against CD20, drugs like brentuximab vedotin or mycophenolate mofetil – which is CellCept – those drugs, too, carry black box warnings for the development of PML; however, the setting in which PML occurs with their use is almost always with a condition that already predisposes you to the development of PML. So with rituximab, for instance, it’s seen with lymphoproliferative disorders, or with transplantation, or with autoimmune diseases in which PML had already been described long before the use of rituximab for the condition. And the same is true with these other drugs.   The second is there’s no latency to the development of the disease, so this is strictly a stochastic event; you may start rituximab today and in two weeks’ time develop PML. There’s no way that somebody’s developed PML in two weeks’ time. What that indicates is that individual was predisposed to developing PML, that virus was already in their brain, it was percolating there, your immune system was suppressing it adequately so it wasn’t expressing itself. And now you’ve done something, you’ve tweaked it a bit and the PML is now expressing itself because you’ve introduced the drug, but the drug fundamentally is not changing the pathobiology of the disease.   Lastly, although we do not have good figures on this, but the best data that I have is that we’re talking about orders of magnitude lower risk with these other drugs. So rituximab, for instance, the risk is probably on the order of 1 in 30,000, or something to that effect. That compared to 1 in 90 when you have all the risk factors that I described with natalizumab. So we’re talking orders of magnitude difference. So I’d suggest that we avoid conflating these drugs when talking about PML risks, and I think that this is something that is generalizable for other risks; I mean, PML is just one risk, but we see other infections and other things that have occurred with other drugs that we’ve employed tweaking the immune system, and I don’t think that one should necessarily put all these drugs that cause these things in the same boat.   MSDF These drugs that are used in other conditions that do in themselves predispose to PML, when they’re used in MS which as a disease does not, on its own, predispose to PML, these same drugs – azathioprine, cyclophosphamide, mycophenolate – add to the risk when you give natalizumab?   Dr. Berger That’s what it looks like. So when Biogen looked at the data that they had available from the initial cases of natalizumab-associated PML, one of the risks that they identified was the increased risk of the development of PML in those individuals that had previously received immunosuppressive therapy. And it really didn’t seem to matter which immunosuppressive therapy it was, it was any immunosuppressive therapy. However, it may be different with the different immunotherapies, it’s simply that the numbers weren’t large enough for one to say that this was particularly associated with azathioprine. People in Europe like to use azathioprine often very early in the course of the disease, so they were seeing a bit more PML than we had seen in the United States at least initially. And it wouldn’t surprise me if there aren’t certain immunosuppressive agents that increase the risk significantly compared to others, but we simply don’t have that data. And what is known is that it really doesn’t matter, any of them can do that.   MSDF Without really having a firm understanding of the pathogenesis of PML – you know the risks but maybe not exactly why it’s occurring – how do you come up with a framework for mitigating risk; is it purely empiric?   Dr. Berger That’s an excellent question. So it turns out that this was a back-of-the-textbook disease; this was the disease that occurred very, very rarely. Between 1958 and 1984 in a review published by Ben Brooks and Deward Walker, there were only 230 cases that they were able to come up with; 1958, of course, is when the disease was first described. So this was a very, very rare disease until the AIDS pandemic where people developed some interest in it, and then it really became interesting when we saw it with natalizumab. And there’s been more resources put into the study of this disease since then, so that we do have a better understanding of the pathogenesis. But in identifying these risks, we’ve worked backwards; you know, we say, alright, what does natalizumab do? So why is it that we see this increased risk?   So in getting back to your question, we know that immunosurveilling the brain is important; so if you have a drug that prevents appropriate immunosurveillance of the central nervosus system, it should not surprise you that the risk of PML is increased. And we do think that the alpha-4 beta-1 integrin inhibition that occurs preventing the entry of JC virus-specific cytotoxic T lymphocytes into the brain is in a large measure – but not completely – contributing to the development of PML. We also know other things. For instance, the virus that we are likely infected with – and the infection occurs very early in our lives; seroepidemiologic studies indicate that most individuals that are infected are infected before the age of 20 – that that virus is a virus that is ubiquitous but incapable of growing effectively in glial tissues; it is a virus found in urine and found in the urinary tract, it’s found in kidney and renal pelvis and bladder, and it’s found in high concentrations in some people’s urine. That virus will not grow in the brain. So something has to happen to the virus.   Does natalizumab change that in some way? Well, we think it does. We think it does that by causing the release of immature B cells; these immature B cells can harbor JC virus, and that virus as these B cells mature there is an upregulation of transcriptional factors that transactivate the virus, it is occurring in a milieu that may uniquely predispose to a genetic rearrangement of the virus enabling it to become a form of the virus referred to as a prototype strain or a neurotropic strain that can grow in the brain. So we think that there are at least two very large barriers that prevent PML that are affected by natalizumab; there may be others. And as we investigate this disease further, our understanding may improve and these explanations I’m telling you will likely be expanded. And, in fact, it may be that some of the thoughts that we have are wrong, because the story with the B cells is actually somewhat hypothetical; there’s some preliminary evidence supportive of it, and that’s why I tell people that I’m fond of Ralph Waldo Emerson’s comment, that consistency is the hobgoblin of small minds. If I stand before you a year from today and tell you something different, it’s only because we’ve learned more about it.   MSDF So how do you mitigate risk and how do you get the point across to patients to let them make informed decisions with you?   Dr. Berger So this is difficult, but we lay the facts out to them. And the facts are that there is this risk of PML, the risk in individuals that are JC virus antibody-negative are very small, the product label puts the risk at less than 1 in a thousand; the belief is that it’s significantly less than that. The fact is that we do see individuals who are JC virus antibody-negative months before the development of PML – it’s rare but it occurs – and there have been studies, including my own, that have indicated that the antibody study doesn’t necessarily mean you’ve never been infected by the virus. So one shouldn’t conflate JC virus antibody negativity with never having been infected, but it is a very good marker for the development of PML, and it is one that needs to be monitored carefully at six month intervals.   So we lay out to the patients that if you’re antibody-negative your risk is infinitesimal and an acceptable risk, and that we monitor you carefully. The second is this is a disease that can be life-threatening, and if not life-threatening certainly severely debilitating – multiple sclerosis I’m talking about – and there are people that have very aggressive disease and will accept the risk of developing PML, knowing that the risk may be 1 in 100, but their risk of developing something that was going to leave them wheelchair-bound and totally disabled is very, very high, and they say I’d rather take the risk of the development of PML.   So we do know what the numbers are. There’s a table that’s been published and gets revised periodically that puts into it JC virus antibody positivity, duration of therapy broken up into 24-month epochs, and prior immunosuppressive use. So we know what the risks are; the highest are in individuals that are treated more than 24 months with the drug, are JC virus antibody-positive, and had previously received immunosuppressive therapies.   MSDF What about monitoring for signs and symptoms of PML if someone does choose to go on some of these drugs?   Dr. Berger Yes, so that’s very, very important. And we do have patients that even in the face of JC virus antibody positivity, we and the patient elect to continue them on the drug. And patients on natalizumab need to be monitored very carefully for the development of PML, and that is a combination of both clinical screening – there is a TOUCH program that queries for the development of symptoms that may be concordant with PML – unfortunately, you also see symptoms of that nature develop in MS patients, as well, so it’s sometimes difficult to tell whether it’s MS or PML – and at that point in time you definitely want to survey them with an MRI. And, in fact, many of us do MRIs at regular intervals in patients on Tysabri attempting to identify the disease – PML – when it is asymptomatic. And those people seem to do best; the prognosis both in terms of disability and in terms of survival is better when you pick the disease up while they’re still asymptomatic, and they have what one would refer to as radiographically isolated PML.   So it’s a combination of vigilance, asking the right questions, performing your physical examination, and obtaining period MRIs, and in those that are JC virus antibody-negative – or even the antibody-positive – repeating that study periodically. And the reason I say that repeating it periodically even in the positive patients is because what’s been demonstrated is that the higher your antibody titer, the greater the risk of developing PML. So there’s a threshold now that’s been identified and individuals above that range have a significantly higher risk of developing PML than individuals who are seropositive but below that level.   MSDF And just to clarify; the TOUCH program is the Tysabri Outreach Unified Commitment to Health? This is what you’re referring to in terms of monitoring for signs and symptoms of PML?   Dr. Berger That is correct. That is the risk mitigation strategy that is FDA-approved and that Biogen has implemented in an effort to decrease the likelihood of PML developing.   MSDF Very good, thank you.   Dr. Berger My pleasure.   [transition music]   Thank you for listening to Episode Thirty-Eight of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]

[intro music]   Dan Keller: Hello, and welcome to Episode Thirty-six of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an extended interview with Jenny Ting, an immunologist who studies the inflammasome, a multi-protein oligomer that’s part of the innate immune system. But to begin, we’d like to tell you something about why we started the MS Discovery Forum.   MSDF, located at www.msdiscovery.org, is an online portal providing news and information about research in MS. We offer a unique combination of news and background articles written by professional science journalists, viewpoints from thought leaders and subject matter experts, and technical resources that enable sharing and analysis of information and open discussion among MS stakeholders in academia, industry, and the clinic. Membership in MSDF is free, and all content on the site is provided on an open-access basis to the entire MS community.   MSDF stands apart for its comprehensive and independent coverage of MS research. Readers can depend on MSDF to report and verify, not merely re-run press releases. MSDF’s overarching goal is to accelerate progress toward clinically useful advances.   We launched MSDF in April 2012 with the aim of filling a knowledge gap in MS research. The plan was to promote collaboration among scientists who are separated by specialized skill sets, institutional boundaries, and geography. It’s well known that these individuals attend different meetings and read different journals. And while it’s common knowledge that scientific breakthroughs and medical advances most typically result from cross fertilization of ideas, in today’s world scientists still do not easily share ideas and collaborate on solutions. We wanted to change that, and to bring thoughts, knowledge and ideas out from the lab into the open to enlighten and inform all stakeholders in the effort to cure MS, including health care providers and people affected by MS.   To that end, we employ the highest standards for independent journalistic reporting, including the use of multiple viewpoints to give a full picture of a finding’s impact. We aim to make scientific findings accessible to everyone, from busy clinicians to cutting-edge researchers to people with MS and their loved ones. We avoid short-cuts, such as the use of jargon, that get in the way of comprehensibility. We highlight the potential clinical impact of the research we cover, even when we’re covering basic research that may be years from direct clinical relevance. And we seek innovative ways to communicate important information to our audience.   [transition music]   Now to the interview. Dr. Jenny Ting is Professor of Microbiology in the Institute for Global Health & Infectious Diseases at the University of North Carolina at Chapel Hill School of Medicine. In addition to MS, Dr. Ting’s research interests include the role of the immune system in infection, inflammation, and cancer. Science Journalist Carol Morton caught up with Dr. Ting at a recent Keystone meeting.   Carol Morton: I appreciate your taking time out to talk to MS Discovery Forum. So we’re at the Keystone meeting on Neuroinflammation in Taos, New Mexico, and you gave a very interesting talk today.   Jenny Ting: Thank you.   Morton: So can you tell us what you’re talking about when you’re talking about the inflammasome and the particular proteins that you’ve been looking at.   Ting: The groups of proteins that we work on are cytokines, and cytokines are made by immune cells. And they have a tremendous impact on inflammatory responses. As you know, in MS there is a big immune component, so these cytokines will influence it. And in most cases cytokines activate the immune system. One of the key cytokines that we’ve studied is called IL-1, interleukin-1 beta; this is the one, for example, that causes fever, inflammation, and so forth. So it’s called interleukin-1 because it was the first one discovered, and it turns out it’s probably one of the most important ones.   So because it’s a master cytokine, and once it goes it kicks off all the other cytokines, so there’s a cascade that goes on. So it could activate other cells to make other cytokines, so it’s like a vicious cycle. Obviously, this becomes a pretty important target to think about. The process that causes this cytokine to be produced is a very big molecule that’s comprised of different proteins. And these different proteins, they are, together, called the inflammasome for inflammation large complex because “some” means large complex. Inflam- is inflammation, as in inflammasome. It’s the name given by Jürg Tschopp.   And so this process where you have this big complex, and as a result you get the cytokine called interleukin-1 beta, what happens is that interleukin-1 beta has now been implicated in so many diseases including arthritis, very rare diseases that causes a lot of inflammatory responses. It’s involved in skin allergies. It’s involved in colitis, you name it, and it’s involved in smoke-induced chronic obstructive pulmonary disease, COPD, that we see advertised on TV. So all of these have this component of this molecule.   Morton: So anything that releases IL-1 beta, inside the cell there’s a cluster of proteins that have to come together to make it.   Ting: Right.   Morton: And then it gets secreted and does its job.   Ting: Yes. And as we learned today, and actually it’s been published, but may be new to some of the audience, is that this whole complex can also be excreted in some ways into the cell, you know, pushed outside of cells so it can go from perhaps one cell to the other. So we have previously found that this can be a complex that’s membrane bound, and that’s called an exosome. So it’s both just like a minicell that goes from one cell to the next and make the next cell inflammatory as well. The speaker today showed that, in addition to that, it can also go out as a complex, perhaps naked. It seems like they are not really membrane bound, so that’s a different form. So it could be different forms that goes out from one cell to the next causing inflammasomal activation in the next cell and therefore perpetuates this IL-1 process.   Obviously, in normal hosts there must be a way to turn off this process, otherwise we would be, you know, a little ball of pus sitting on a chair. So obviously these don’t go on forever. The problem with chronic inflammatory diseases is many of these things, they don’t go on probably all the time, but they do increase. So what we did is really look at mice lacking genes that can make these proteins. This complex is usually comprised of at least three components; you knock out one and you can’t make IL-1 anymore. Actually, I should say five components. So we did that, and what we found was that if you take this out, the models of MS suggests the well-known mouse model, EAE, and another model that we’ve been really pushing, although it was initially worked on in the late 1960s and early 70s, this model of neurotoxicant-induced demyelination. In both of those models this process of inflammasome/IL-1 turned out to be bad.   So if you remove this process, the disease is much more attenuated. So that’s one of the really interesting parts about what we had found is that potentially this could be a target. And the good thing is that there is certainly some companies that have successfully made anti-IL-1s. So there is an IL-1 receptor antagonist that inhibits this process. There is an antibody against IL-1 that will inhibit this process. So certainly there are therapies, if this is true, that this is part of the MS problem that this could be used as a therapy.   The other thing we have found, which I didn’t get a chance to talk about, is that we did look at the remyelination phase and found out that, for example, IL-18 is not very good for remyelination. Of course, remyelination is what everybody would like to have, is a reparative process. And so one possibility is, can we block the IL-18 pathway, and can we get better remyelination processes. So those are some of the thoughts that we have.   Morton: So have you examined a number of the ILs from 1 to 18 or…?   Ting: No, because 18 is the product. So this inflammasome actually has many different targets. One of them is IL-1 beta; that’s the key one. Another one is IL-18. So we went from there to look at what’s downstream of the inflammasome and found out that IL-18 actually has a role both in making MS disease models worse and in reducing the extent of remyelination. So it doesn’t look like it’s a great protein to have around. So the question is can we try to inhibit this molecule.   Morton: Just to make sure that I’m clear on that: the inflammasome is a cluster of proteins that come together in an immune cell, like a T-cell, or a…   Ting: Usually it’s a macrophage or a microglia or an astroglia.   Morton: A macrophage or a microglia. And then that makes the IL…   Ting: So what you have is – I don’t know if the audience might be familiar with the coagulation pathway where you have one protein that has to be cleaved into a smaller protein. Then this protein B goes and cleaves a second protein from a bigger form to a smaller form. And the smaller form, in every case, is the mature protein that has activity. The bigger protein is the inactive form that doesn’t do anything. So this exactly the same. Pro-IL-1 has to be cleaved into IL-1. Pro-IL-18 has to be cleaved into IL-18. And what that cleavage process is this inflammasome complex producing an enzyme that will cleave these proteins.   Morton: So the inflammasome is like Edward Scissorhands running around cutting proteins making them active.   Ting: Yes, that’s a great analysis. So it’s just exactly like that. The inflammasome produces this – like you said – Edward Scissorhand that then this guy can go and prune the roses and prune the bushes, and they’re different, and they have different functions.   Morton: And it’s the starting block for the activity of the IL-1 and IL-18.   Ting: Right, so the bushes are like – if the roses are the IL-1, you can decorate it; you can give it to somebody; you can make it into a bouquet. So that’s the kind of idea. And then if you have a bush, you know, you can potentially do other things with it. Or if he’s cutting some edible plants you can use that for cooking. So that’s the whole idea. Whatever you produce has different effects. And it turns out IL-18, in our hands, looked like it’s not a good molecule. We have previously found that a cytokine called TNF, which has different roles depending on what it binds. So if it binds to TNF receptor 1, then it’s not so good. If it binds to TNF receptor 2, it actually enhances remyelination, so again, something you want.   And there’s recent talks and there are small molecules where people tried to activate the TNF receptor 2 pathway, and they found that that really enhances the remyelination process. It’s kind of really neat; if you can dissect these pathways well enough, then you might be able to use drugs to target MS.   Morton: So what are the next questions that you’re asking? Where are you going from here?   Ting: So we have a number of directions. Certainly, like I say, I raised the concept of IL-18; so can we target that molecule? In our own lab we’re also looking at several other pathways. So we have found a pathway that’s really important for cell-cell interaction that’s important for MS activation. And the molecules are called plexins and semaphorins. And this is a pair of proteins that seems to activate the immune system especially during MS. So we’ve done that in disease models, and we actually produce a blocker of that pathway. And we have treated mice, and they look much better. We showed that when they’re going through relapse, we can actually prevent them from coming back with a relapse.   So, very similar to some other MS drugs that are on the market, we’d like to think about this as additional possibilities. So those are some of the things that we’re doing.   Morton: What cells are these on?   Ting: These are T-cells and dendritic cells so they’re…   Morton: They’re talking to each other.   Ting: Yes, exactly, they’re talking to each other. And in an MS situation they talk to each other, they activate T-cells, which destroys the myelin. So if you can block that interaction, many of the drugs that are used for MS actually are targeting exactly that interaction pathway. For example, Tysabri is one that’s not so much dendritic cells and T-cells, but it reduces T-cell migration through the vasculature into the blood brain barrier. So that’s one of them where they block T-cell activation. So we are trying to block T-cell activation as well, but at the face of these two cell types.   Morton: If the inflammasomes, if they were superheroes or characters in an Oscar-winning movie, what would their personalities be, do you think?   Ting: I think they would be very powerful because they impact a lot of disease processes, yet they have very strong roles so that, when they’re used properly, they can defend against all sorts of stuff. Whey they’re used improperly, they can really cause a lot harm. So if they’re a superhero, people always say Batman has a dark side, right, a really dark side and a really good side. Maybe that’s what they are.   Morton: That’s a good analogy.   Ting: They’re not like Superman because Superman seems like all good.   [transition music]   Keller: Thank you for listening to Episode Thirty-Six of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]

Today in FirstWord:

Today in FirstWord:

Today in FirstWord:

I Alkymisten denne gang har vi både lytterspørgsmål og et Skype-interview. Hør Jens få svar på spørgsmålet om, hvorvidt han kan tage LDN sammen med Tysabri, og lyt også til Marianne, som har haft attakvis-sclerose i 15 år, og nu har taget LDN i et år. Denne udsendelse sætter fokus på, hvad du kan forvente, når du går i gang med LDN, og hvad du skal være specielt opmærksom på.

I podcast 40 kan du møde Mette Bryde Lind, som siden begyndelsen af 2010 har siddet i direktørstolen i Scleroseforeningen. Hvad kan vi medlemmer så forvente af vores nye direktør? Hvordan bærer man sig ad, hvis man skal gøre alle glade, men stadig vil have en handlekraftig og demokratisk forening? Hvad er Mettes holdning til de udfordringer som medlemmerne og foreningen står over for? Hør bl.a.: - hvorfor ikke Tysabri til alle? - hvem bestemmer hvad der forskes i? - forskes der i CCSVI? Mette er optimist når det gælder foreningens fremtid, selv om andre foreninger oplever medlemsflugt og dalende interesse. Scleroseforeingen skal styrkes, bl.a. ved at give større indflydelse til det enkelte medlem, og anerkende mangfoldigheden - også når man skal signalere til omverdenen hvad sygdommen er. ... Dette podcast er publiceret med hjælp fra PodConsult.dk og Hindenburg.

This Podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Ted Burns interviews Dr. Hans Dieter Katzberg about the AAN guidelines on treatment for muscle cramps. In the next segment, Dr. Ryan Overman is reading our e-Pearl of the week about coat hanger sing in multiple sclerosis atrophy. In the next part of the podcast Dr. Beau Bruce interviews Dr. Robert Naismith for our Lesson of the Week about natalizumab (Tysabri). The participants had nothing to disclose except Drs. Burns and Katzberg. Dr. Burns receives a stipend as Podcast Editor for Neurology®, performs EMG studies in his neuromuscular practice (30% effort), and received compensation for a presentation on MG-QOL15, given to study investigators of eculizumab in myasthenia gravis.Dr. Katzberg has received funding for travel from the Muscular Dystrophy Association.

Denne gang kan du høre Bjørn Sperling (Biogen Idec) fortælle om PML og Tysabri. Tysabri er af mange blevet kaldt "vidunder-medicinen", eller også frygtet som "den medicin man risikerer at dø af". Rix pod forsøger at nuancere billedet, ved at lade den medicinske direktør hos producenten for Tysabri besvare en række spørgsmål. Hør bl.a.: - hvad gør I for at opdage nye tilfælde af PML? - hvad skal man selv være opmærksom på hvis man tager medicinen? - er Tysabri god nok? Så kan du også høre om Rix's frygt for svineinfluenza, og hans overvejelser om vaccinen. Og så er Rix pod blevet nomineret til European Podcast Award, og efterlyser din stemme! ... Dette podcast er publiceret med hjælp fra PodConsult.dk og Hindenburg.

In episode 26 of This Week in Virology, hosts Vincent Racaniello, Alan Dove and guest Rich Condit converse about induction of polyomavirus replication in multiple sclerosis patients treated with the MS drug Tysabri, the extent of human polyomavirus infection, selection of influenza vaccines for the 2009-10 season, cowpox virus transmission from animals to humans, vaccinia-like virus infecting humans and cattle in Brasil, and poxviruses. Links for this episode: JC virus, Tysabri, PML, and mefloquine at virology blog Seroepidemiology of polyomaviruses in human Next season’s influenza virus vaccines and how they are selected Cell-culture propagated smallpox vaccine Cowpox tranmission from rats to humans ( Germany and France) and from cats to humans in Italy Vaccinia-like virus infecting cows and humans in Brasil When good vaccines go wild (review) Mosquito Map (thanks Duncan) Pfeiffer & Kirkegaard paper on quasispecies and virulence in mice Science blog of the week: Coevolvers by Devin Drown Science podcast pick of the week: QuackCast Science book of the week: Listen to the Music: The Life of Hilary Koprowski by Roger Vaughan