Podcasts about aubagio

Welcome to Living Well with MS, the podcast that empowers you to take control of your health and wellbeing. Today we're sharing the highlights from our ‘Ask Aaron' webinar, recorded in front of a global audience, with the incredible Dr Aaron Boster. Dr Boster is a board-certified neurologist who specialises in MS, and we're delighted to have him answering a huge range of questions from our community! From medications to MRI's and pregnancy to cold showers, Dr Boster gave us so many brilliantly informative answers - we hope you find this episode really useful. Let us know what you think!     Watch this episode on YouTube here. Keep reading for the key episode takeaways.     Topics and Timestamps:    01:49 Defining benign MS  05:05 How to get the most out of your time with your neurologist  09:32 The DMTs that help with brain atrophy  09:46 MRI's as a way to show the rate of brain atrophy  18:20 Aubagio for secondary progressive MS  22:11 The future of Ocrevus dosing guidelines and becoming pregnant on ocrelizumab  26:31 Treating MS-relating dystonia  28:37 Treatments for MS-related bladder dysfunction   35:15 Low-dose Naltrexone for MS  39:00 The benefits of cold showers   39:38 Immune reconstitution therapies   43:22 Managing MS with diet and exercise   To join us live for the next webinar or watch the original presentation head to our website overcomingms.org    More info and links:   Dr Boster was on five 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)  S5E5 Webinar highlights from Ask Aaron with Dr. Aaron Boster  S5E36 Webinar Highlights: Ask a Neurologist with Dr Aaron Boster  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. 

Teriflunomid (Aubagio) ist als Immuntherapie für Patienten mit milder bis moderater schubförmiger MS ab 10 Jahren zugelassen. Den vollständigen Artikel zum Nachlesen findest Du auf meinem Blog: https://ms-perspektive.de/264-teriflunomid Diesmal geht es um Teriflunomid, das unter dem Handelsnamen Aubagio bekannt ist. Die Immuntherapie wird bei leichten bis moderaten Verläufen von schubförmiger MS eingesetzt. Teriflunomid hat einen breiteren Wirkmechanismus und gehört zu den immunmodulierenden Medikamenten. Bitte denke daran, dass ich hier nur einen Überblick geben kann. Wende dich an deinen Neurologen und deine MS-Schwester, um dich ausführlich über die Wahl der richtigen Therapie für dich beraten zu lassen. Denn es sollte dein kompletter Gesundheitszustand bekannt sein sowie deine Ziele, Wünsche, Ängste und Vorlieben. Inhaltsverzeichnis Allgemeine Informationen Wie wird Teriflunomid (Aubagio und Generika) bei den Immuntherapien eingestuft? Wofür ist Teriflunomid (Aubagio) zugelassen? Wie sieht die Situation für spezielle Patientengruppen aus? Wer sollte Teriflunomid meiden? Wie wirkt Teriflunomid? Wie wird es eingenommen? Wie wirksam ist Teriflunomid (Aubagio und Generika)? Risiken und Nebenwirkungen von Teriflunomid (Aubagio und Generika) Impfungen Quellen Schlussbemerkung Quellen Für die Erstellung des Inhalts habe ich die folgenden Quellen verwendet: Qualitätshandbuch der KKNMS zu Teriflunomid (Aubagio) MS-Selfie Infokarten von Prof. Dr. Gavin Giovannoni Deutsches Multiple Sklerose- und Kinderwunschregister (DMSKW) Informationen aus dem deutschen Interview mit Prof. Dr. Barbara Kornek zur pädiatrischen MS DMSG-Informationen zu Teriflunomid DECIMS-Informationen über Teriflunomid Schlussbemerkung Bitte denke daran, dass es nicht das eine gute Medikament gibt, das allen hilft, sondern dass immer abgewogen werden muss, was für die jeweilige Person am besten geeignet ist. Auch andere Krankheiten, persönliche Ziele und Vorlieben müssen berücksichtigt werden. Dein Neurologe und die MS-Schwester sind die richtigen Ansprechpartner und können individuelle Empfehlungen aussprechen. Dieser Artikel dient nur zu Informationszwecken und stellt keine Empfehlung dar. Was dem einen hilft, muss dem anderen nicht helfen. Ich hoffe, dass du zusammen mit deinem Neurologen und deiner MS-Schwester schnell die richtige Immuntherapie für dich finden wirst. Und dass du ein erfülltes, glückliches und selbstbestimmtes Leben mit MS führen kannst, unterstützt durch einen gesunden Lebensstil und eine Portion Glück. --- Vielleicht möchtest du auch einen Blick auf die Beiträge zu den anderen Immuntherapien werfen: Dimethylfumarat (Tecfidera) und Diroximelfumarat (Vumerity) Glatirameracetat (Copaxone, Brabio) Interferon-beta (Avonex, Betaferon, Extavia, Plegridy, Rebif) 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.

Fire, flood, record-setting heat, tropical storm, earthquake -- we've seen it all in the past several weeks! Natural disasters can present a whole series of unique challenges for people affected by MS.  Last year, I had an opportunity to talk about disaster preparedness for people affected by MS with Mary Casey-Lockyer, the Senior Medical Advisor to Disaster Operations at the American Red Cross. As extreme weather events become a more frequent and regular occurrence in our everyday weather patterns, I thought it made sense to revisit my conversation with Mary. Mary has just recently retired from her position at the Red Cross, but I think you'll find her tips and strategies as worthwhile and valuable today as they were a year ago. We'll also tell you about Tyruko, the first biosimilar to receive FDA approval for treating MS (and we'll make sure you know exactly what biosimilars are and where they fit in the spectrum of pharmaceutical treatments). We'll share the results of an important clinical trial that may cause experts to re-think when MS begins and when it should be treated. We have a lot to talk about! Are you ready for RealTalk MS??! This Week: Revisiting disaster preparedness for people affected by MS  :22 The FDA has approved the first biosimilar for treating MS  1:38 Results from a clinical trial show that treating RIS with Aubagio significantly reduces the likelihood of developing MS  4:34 Mary Casey-Lockyer discusses how someone living with MS should prepare for a natural disaster   7:39 Share this episode  28:13 Have you downloaded the free RealTalk MS app?  28:33 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/313 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: Teriflunomide and Time to Clinical Multiple Sclerosis in Patients with Radiologically Isolated Syndrome https://jamanetwork.com/journals/jamaneurology/articles-abstract/2808741 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 313 Guest: Mary Casey-Lockyer Privacy Policy

Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, reads a news report on ATA188, a treatment targeting the Epstein-Barr virus which could be integral in treating progressive MS. He also reads a news article reporting on how ublituximab works better than Aubagio at easing disability in patients with relapsing MS. =================================== 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, discusses how ALITHIOS trial participants who started on Kesimpta were about four times more likely to have no MS symptoms than those starting on Aubagio. He also reads “Comparing Cases of Multiple Sclerosis Leads to a Logical Fallacy” by Benjamin Hofmeister, from his column “Chairborne.” =================================== 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, discusses how MS can increase the risk of potentially life-limiting problems like pneumonia, as a team of scientists in the U.S. and China conducted an study to identify the link between MS and mortality risk. He also reads “MS News That Caught My Eye Last Week: Evusheld, Immunotherapy, Blood Test, Aubagio”, 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 more than half of multiple sclerosis patients on Aubagio showed no evidence of disease activity after two years, according to a study. He also reads”A Road Trip From Florida Maryland With No Bladder Incontinence”, by Ed Tobias, from his 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, covers how MS patients on Mavenclad are less likely to experience a disease relapse than those on other oral DMTs like Gilenya, Tecfidera, or Aubagio. He also reads “The Double-Edged Sword of Fatigue Medications”, from Beth Ullah's 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/

Multiple Sclerosis News Today's multimedia associate, Price Wooldridge, discusses how treatment with Tecfidera led to fewer relapses in relapsing-remitting multiple sclerosis patients than Aubagio or injectable immunomodulators. Plus, Price reads the column by John Connor, Fall Down, Get Up Again, “It's Just One of Those MS ‘Snow Days'.” =================================== 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/

One of the things that people affected by MS seem to worry about every year is the flu vaccine. And the question is always the same -- is it safe for someone with MS to get a flu shot?  This year, that question and its accompanying anxiety are compounded by the COVID-19 pandemic. Is it safe for someone with MS to get a flu vaccination during the pandemic? Is it safe for someone with MS to get a COVID-19 vaccination when one becomes available? And what about the impact of MS disease-modifying therapies on the effectiveness of any vaccination?     My guest is Dr. John Ciotti, a board-certified neurologist and clinical fellow at Washington University in St. Louis, Missouri. Dr. Ciotti is with us to answer those important questions. We're talking about flu shots and other vaccinations, and we're even talking about how a COVID-19 vaccine -- which doesn't exist today -- is likely going to affect people with MS who are on disease-modifying therapies. This is a conversation you don't want to miss because the perfect antidote to worrying is getting your hands on good, credible information.   We're also talking about the very positive outcomes of two clinical trials comparing ofatumumab to Aubagio. It's likely that next month, ofatumumab (Arzerra) is going to receive FDA approval for treating MS, so these clinical trial results are something you'll want to know about.   We'll share the results of a study that should give you the most important reason yet to include exercise as part of your regular routine and we'll point you toward the new exercise resources that have been created especially for people living with MS.    The National MS Society conducted a survey to measure how the COVID-19 pandemic was affecting people living with MS. We'll share some of the highlights from the survey and we'll even remind you where to find the resources that were requested most by survey respondents.   And we'll tell you about the very first study to measure the incidence of MS in China.    We have a lot to talk about! Are you ready for RealTalk MS??! National MS Society survey measured the impact of the COVID-19 pandemic on people living with MS  1:54 Clinical trial data shows ofatumumab outperforms Aubagio  4:08 Research shows that exercise preserves key areas of the brain among people with MS   6:53 Research team is first to report the incidence of MS in China  10:00 My Interview with Dr. John Ciotti  12:55 Share this episode  28:25 Please leave a rating & review  28:48 DUNK MS is happening Saturday!  29:01 Please Support the National MS Society COVID-19 Response Fund  29:40 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/154 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.comPhone: (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 Give RealTalk MS a Rating and Review National MS Society's Ask An MS Expert Video Replay What You Need to Know About Coronavirus (COVID-19) Effects of MS Disease-Modifying Therapies On Responses to Vaccinations: A Review RealTalk MS Episode #148: Updated guidance on COVID-19 and each of the available disease-modifying therapies STUDY: Ofatumumab vs Teriflunomide in Multiple Sclerosis STUDY: The Importance of Physical Activity to Preserve Hippocampal Volume in People with Multiple Sclerosis: A Structural MRI Study National MS Society Recommendations for Exercise & Physical Activity For ALL People with MS VIDEO: Stretching Tips for MS VIDEO: Aerobic Exercise Tips for MS VIDEO: Breathing Exercise Tips for MS STUDY: Incidence of Multiple Sclerosis in China: A Nationwide Hospital-Based Study National MS Society COVID-19 Response Fund Join the RealTalk MS Facebook Group Download the RealTalk MS App for iOS Download the RealTalk MS App for Android Give RealTalk MS a Rating and Review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 154 Hosted By: Jon Strum Guests: Dr. John Ciotti Tags: MS, MultipleSclerosis, MSResearch, MSSociety, Vaccinations, COVID-19, RealTalkMS Privacy Policy

Blood Shortage 1. Usage = 32K pints of blood used every day in US 2. Type of blood in short supply = Type “O” 3. Impact – 4.5M a. 220mg-250mg of Iron lost for every donation – 24-30 weeks to replace iron b. Normal Iron levels = 10-30 mmol/L (also ferritin < 10mcg/L) 4. Donor requirements (Red Cross) – Good health, weight >= 110 pounds, >= 17 years old a. Eat iron rich foods (spinach, red meat, fish, poultry, beans, iron fortified cereals and raisins) b. Drink an extra 16 oz fluids c. Avoid fatty foods (hamburgers, fries, or ice cream) d. No upper age limit 5. OTC and homeopathics, herbals, nutritional supplements are acceptable 6. Anti-depressants, Xanax, ADHD drugs -- OK 7. Restrictions (Red Cross) – anyone who has used self-injected non-prescription drugs, anyone who lived in UK for >= 3 months (and other parts of Europe) since 1980-1996 due to mad cow disease (bovine spongiform encephalopathy), heavy periods a. Coronary artery disease b. Beta blockers c. HIV d. Hepatitis e. Active infection – wait 10 days after last antibiotic f. Autoimmune disease g. Receive a transfusion – wait 12 months 8. What categories of medications prevent people from giving blood? a. Acne meds – Isotretinoin (d/t birth defects) b. Finasteride and dutasteride (d/t birth defects) c. Psoriasis meds – Soriatane (acitretin) – wait 3 years d/t severe congenital birth defects d. Antiplatelet meds – wait 7-14 days for platelet donations e. Blood thinners – blood doesn’t clot f. Growth hormone injections g. Multiple sclerosis medications – Aubagio – wait 2 years d/t birth defects 9. Medications that can’t be used to give blood (must wait one month until you can give blood) a. Accutane, Amnesteem, Absorica, Claravis, Myorisan, Sotret, Zenatane (isotretinoin) b. Proscar (finasteride) c. Propecia (finasteride) 10. Recovery a. Blood replenished within 24 hours b. Red cells take 4-6 weeks c. Must wait 8 weeks between giving blood ______ Make sure to subscribe to get the latest episode. Contact Us: Pharmacy Benefit News: http://www.propharmaconsultants.com/pbn.html Email: info@propharmaconsultants.com Website: http://www.propharmaconsultants.com/ Facebook: https://www.facebook.com/propharmainc Twitter: https://twitter.com/ProPharma/ Instagram: https://www.instagram.com/propharmainc/ LinkedIn: https://www.linkedin.com/company/pro-pharma-pharmaceutical-consultants-inc/ Podcast: https://anchor.fm/pro-pharma-talks

Research is the engine that drives us toward better understanding MS, better treating MS, and one day, curing MS. My guest on the podcast is Dr. Larry Sherman, who plays a vital role on the front lines of MS research. We're talking with Dr. Sherman about some of his most significant research and his unique research lab.      We're also talking about two important victories for MS Activists. We'll tell you about the EMA approval of Gilenya for treating pediatric MS, the FDA approval of a generic for Aubagio, new technology that will enable people with MS to pilot their wheelchairs by flexing a couple of facial muscles, and the rehab technique that can benefit Olympic athletes and people living with MS.   We have a lot to talk about! Are you ready for RealTalk MS?! ___________ MS Activists Have Something to Celebrate   0:22 National Neurological Conditions Surveillance System Will Study Data for MS 4:48 European Medicines Agency Approves Gilenya for Pediatric MS  6:41 FDA Approves Generic for Aubagio  8:21 New Technology Lets You Pilot a Wheelchair By Flexing Facial Muscles  9:32 Motor Imagery with Verbal Cues & Music May Lead to Improved Walking, Fatigue & Quality of Life for People Living with MS  11:31 My Interview with Dr. Larry Sherman  15:34  ___________ LINKSIf 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 Download the RealTalk MS App for iOS Download the RealTalk MS App for Android National MS Society: Get Involved & Advocate For Change Limbitless Solutions Project Xavier STUDY: Effects and Mechanisms of Differently Cued and Non-Cued Motor Imagery in People with Multiple Sclerosis: A Randomised Controlled Trial Oregon National Primate Research Center 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 67 Hosted By: Jon Strum Guest: Dr. Larry Sherman Tags: MS, MultipleSclerosis, MSsociety, ACA, MSActivist, Gilenya, Aubagio, Limbitless3D, RealTalkMS

[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.

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.  

Full Transcript: [intro music] Host – Dan Keller Hello, and welcome to Episode Seventy-three of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. Today's interview features Donna Osterhout, a cell biologist at Upstate Medical University in Syracuse, New York, USA. Dr. Osterhout talks about a new way of looking at myelin-making cells, which move and change shape in dramatic ways. Current MS drugs take aim at preventing new immune damage. In the future, researchers hope to figure out how to repair myelin and restore function. But first, let’s look at new content on MS Discovery Forum. Spring brings rain, flowers, and a bouquet of scientific meetings related to multiple sclerosis. See the list at msdiscovery.org under the tab “professional resources.” MSDF sent the only journalist to cover the recent meeting of the American Society of Neurochemistry in Denver, but you can count on a blitz of news from the media pack at the next meeting on the calendar – the American Academy of Neurology in April, happening this year in Vancouver, BC, Canada. The number of research papers about multiple sclerosis has doubled in the last 10 years, and many findings are first reported at meetings before publication. Moving on, let’s sample a few of the new papers we found in our weekly PubMed search of the world’s largest medical library, the National Library of Medicine. You can link to each week’s list of curated papers at msdiscovery.org. Related to this week’s podcast, a new paper reviews the latest research about the molecular cues that allow precursor cells to mature and go through the stages of making myelin. These cues come from axons and from other surrounding tissue. Clinical drug development efforts focus on overcoming inhibitory cues, such as with the experimental agent anti-LINGO-1, now completing phase 2 clinical trials for MS and acute optic neuritis by Biogen. The review authors suggest future drugs to repair myelin could boost permissive and promotional cues, which may go wrong in disease. The paper is published by researchers at the Virginia Commonwealth School of Medicine in the journal Experimental Neurology. Another report updates the Cochrane systematic review on teriflunomide, a daily oral medication for relapsing remitting MS marketed under the brand name Aubagio by Sanofi Genzyme. Cochrane’s systematic reviews are ranked among the highest level of medical evidence, because of the rigorous independent analysis of multiple studies, including randomized controlled trials. The authors write that, as a single drug, the high dose of teriflunomide was as effective as interferon beta 1-a, while the low dose was less effective. They recommended longer follow-up analyses and noted that the available evidence was low-quality, as well as subject to bias, in part because all studies were sponsored by pharmaceutical companies. In general, side effects were mild to moderate and do not usually lead to treatment being stopped, but the higher dose is more prone to cause these side effects. The study is available in the Cochrane Library. The final editor’s pick this week takes a fresh look at how medical images transform a patient’s view of her own body. The paper describes an artistic collaboration between Devan Stahl, a bioethicist at Michigan State University with multiple sclerosis, and her sister Darian Goldin Stahl, a printmaker. The resulting art – some of it life sized – superimposes Devan’s narrative and MRI images with body photos. Devan wrote in the paper that the art collaboration has made it easier to talk about her MS. The paper is published in the journal Medical Humanities. If you're in town for the big Neurology meeting, you can catch Darian’s artist talk on April 17 at 2 pm at Malaspina Printmakers in Vancouver, Canada. [transition music] And now to our interview. We caught up with Donna Osterhout in Denver, Colorado at the March meeting of the American Society for Neurochemistry. She organized a symposium that told a new story about myelin-making cells. In different labs, researchers started looking for clues in the radical shape changes that occur in the cells in their normal process of making myelin. These oligodendrocyte precursor cells sprout “arms” to reach out and touch neighboring axons. Then they push out slabs of fatty membrane and wrap them around and anchor them to the axons. In multiple sclerosis and other demyelinating diseases, the immune system attacks this myelin wrap, and the cells cannot keep up with repair. The unprotected axons may be damaged or destroyed, causing the worsening disability of MS. Learning how the cells make myelin may pave the way toward new therapeutic agents to repair demyelinated axons and restore function. Dr. Osterhout spoke with our executive editor, Carol Cruzan Morton. Interviewer – Carol Cruzan Morton So we are here, in Denver, at the annual meeting of the American Society for Neurochemistry, and you've put together a very interesting panel on a new way of looking at myelin. So can you sort of set the scene for us when you're talking about the myelin research that you're working on? Interviewee – Donna Osterhout Well, myelin is a specialized membrane that is wrapped around axons; it occurs in the last step of development. And oligodendrocyte progenitor cells are the cells that form myelin. They are going to migrate out through the developing brain and they're going to extend processes that come in contact with axons that need to be myelinated. And when they get the appropriate signals, they are going to start a process by which they synthesize and extend a large membrane, which wraps around this axon many times and compacts and forms myelin. The way that this happens has been a mystery thus far, but recent research suggests that there has to be a lot of rearrangements of the internal cytoskeleton for this to happen. And so the symposium was organized to talk about how the cytoskeleton might be changing to allow for this membrane wrapping and myelin formation. MSDF Can you tell me more about the cytoskeleton? Dr. Osterhout The cytoskeleton is comprised of specialized proteins within cells, and every cell has a cytoskeleton; it gives it shape, but it also allows it to migrate, differentiate, and extend processes, so cells wouldn't be able to do much without a cytoskeleton. And in the case of oligodendrocytes, there are a lot of cytoskeletal rearrangements that occur to allow for myelination. MSDF Can you tell me more about the emerging view about how myelination may be working based on this new way of looking at it? Dr. Osterhout Initially, we know that there are early signals that trigger extensive process outgrowth from these cells. Once the axon sends a signal to the oligodendrocyte progenitor cell, they start to put out many, many processes, synthesize myelin proteins, and make this big membrane that will wrap around the axon. What winds up happening is that in the past everybody thinks that we've needed a driving force so that something pushes this forward, and it had been thought that perhaps the actin cytoskeleton was the driving force behind this. The newer research indicates that initially you have to have signals that trigger the process outgrowth, but this is followed by an actual disassembly of the actin cytoskeleton. So it's somewhat opposite of what we had thought previously. MSDF Can you tell me more about the steps that are involved in the process of myelinating that you and your colleagues have been discovering? Dr. Osterhout Well, the initial step is the activation of a cellular kinase called Fyn tyrosine kinase; this is the earliest step in the differentiation of these progenitor cells. Fyn will be activated by any number of signals from the axon including, for example, glutamate that's released. And once Fyn is active, it initiates a rearrangement of cytoskeletal proteins called microtubules in order to facilitate process outgrowth so we can extend processes to form this membrane. In later stages, then we have Fyn helping to trigger the synthesis of myelin proteins, and then you start to get other proteins active that will disassemble the actin cytoskeleton. There is even some evidence that perhaps myelin basic protein can do this. So Fyn signaling will turn on early and promote the synthesis of myelin basic protein, and then myelin basic protein will proceed down these processes and help to disassemble the actin cytoskeleton so the membrane can wrap around the axon. MSDF Can you describe what the cells look like when they're going through this process? Dr. Osterhout Well, this is really interesting to study, especially in vitro. You can set up myelinating cultures of oligodendrocyte progenitor cells. They're very simple cells, they're like bipolar, two to three processes, and that's the earliest progenitor that we might look at. But once you trigger differentiation, they start to put out processes in a somewhat predictable manner. They will first extend five processes, and then these five processes start branching And they produce these intricate branches. At some point these mature cells will actually look like a lace doily; they are spectacular with the cell body in the center and all these highly branched processes surrounding it. And then you see a transformation of these processes into this huge membrane sheet, and in the absence of an axon it's just going to cover the tissue culture dish; it's amazing how large this can get. But if you had an axon in the culture, this membrane sheet would just form myelin. They would form a myelin segment wrapping around the axon. MSDF That’s so interesting. And then can you say, adding to that picture, the steps that are happening in those process that you and your colleagues have been discovering? Dr. Osterhout So when you have the initial process outgrowth, you have Fyn tyrosine kinase active, and that facilitates the initiation and that extensive process outgrowth. But the transition between the process outgrowth and the formation of membrane sheets is going to be the disassembly of the actin cytoskeleton. MSDF And that's the big news is that the actin cytoskeleton is breaking down instead of pushing the myelin forward as it's making its multiple wraps around? Dr. Osterhout Yes, this seems to be the way that this is happening mechanistically. The formation of that myelin membrane requires the actin disassembly, and two of the speakers that we had in our symposium gave evidence to this, using several different experimental systems. And then ultimately when you're going to anchor this myelin sheath, and you can get some specializations in the axonal membrane, and this is what one of the speakers talked about, anchoring the perinodal loops, kind of the ends of the myelin segment. And so we have a process by which we have extensive process outgrowth triggered by Fyn. Then once you get the process outgrowth, you have actin disassembly and you form these membrane sheets, and then they would wrap around the axon, forming myelin, and then you would stabilize it with special proteins in the axon that stabilize the ends at the perinodal loops. MSDF So what does this have to do with diseases like multiple sclerosis? Dr. Osterhout That's a very good question. If we understand what goes on in development, then we might be able to predict how we could facilitate this process in a demyelinating disease like multiple sclerosis. We do have oligodendrocyte progenitor cells in our brain and spinal cord. They persist as a population throughout adulthood. And any time you have a lesion or a trauma to the brain, and especially if you get demyelination, then you'll have these cells migrate to the area of demyelination. And if we can encourage them to remyelinate, they would undergo the same steps. We have shown evidence that the inflammation and other conditions in a demyelinating disease upregulates chondroitin sulfate proteoglycans, and these can actually inhibit the process outgrowth and remyelination by oligodendrocytes, because they ultimately inhibit the activation of Fyn kinase. So if you're considering a disease process, you want to stimulate these steps. And you want to look for agents that might trigger and make sure that these steps proceed, or neutralize things that would be present in the lesion that would inhibit this. MSDF One interesting aspect of your work, and perhaps of science more generally, is that some of these discoveries with relevance to multiple sclerosis come from your work on spinal cord injury. Can you talk about how that works in science? Dr. Osterhout Well, spinal cord injury is another type of lesion, it's a specialized lesion; you have damage to axons as well as demyelination due to trauma. But in diseases in general in the brain and the spinal cord, whenever you have an injury process or inflammation or some kind of destruction of tissue, you get an inflammation and immune influx, and you will get a process called reactive gliosis. And this is common to many diseases that you see in the brain. For example, you can see it easily in spinal cord injury, it's been well documented. You can see these proteoglycans' reactive gliosis in multiple sclerosis, you can see it in Alzheimer's disease, Parkinson's disease, and other conditions, because they all have a common element that you've got some kind of inflammation occurring and tissue destruction occurring at a specific place. MSDF Getting back to multiple sclerosis and the work on how cells myelinate axons, what are the next big questions that you and your colleagues are asking? Dr. Osterhout Well, there still are a lot of questions about exactly how this myelination process is accomplished even during development; we don't fully understand all of the triggers that would activate this process. And, likewise, we don't always understand things that might inhibit this process. So we need to more fully characterize what's going on in development so that we can take a look at it in the remyelinating situations, either in spinal cord injury, or multiple sclerosis, or any other demyelinating condition. MSDF Well, that's really interesting. Well, thank you for taking the time to explain the research. Dr. Osterhout And thank you for your interest; it's been my pleasure. [transition music] MSDF Thank you for listening to Episode Seventy-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 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]  

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