Podcasts about Dystrophin

ONCE UPON A GENE - EPISODE 204 From Heartbreak to Hope - With CEO of Parent Project Muscular Dystrophy, Pat Furlong When doctors diagnosed her two sons, Christopher and Patrick, with Duchenne in 1984, Pat didn't accept “there's no hope and little help” as an answer. Pat immersed herself in Duchenne, working to understand the pathology of the disorder, the extent of research investment and the mechanisms for optimal care. Her sons lost their battle with Duchenne in their teenage years, but she continues to fight—in their honor and for all families affected by Duchenne. EPISODE HIGHLIGHTS How and when did you realize something was wrong? While other children played energetically, her sons would engage in quieter activities like coloring. Initially, she believed she simply had well-mannered children. However, she soon realized that her children were hesitant to engage in certain physical activities, such as running. While other children played energetically, her sons would engage in quieter activities like coloring. Initially, she believed she simply had well-mannered children. However, she soon realized that her children were hesitant to engage in certain physical activities, such as running up and down stairs or jumping. Concerned, she sought advice from various individuals, including her physician husband and his colleagues. Despite her genuine worries, many dismissed her concerns, labeling her as an overly anxious mother. This dismissal set her on a path of determination to find out more about her children's condition How did you begin? The beginning of her journey was marked by a mix of determination and desperation. Shortly after receiving a diagnosis about her children, she took a bold step by borrowing $100,000 from the bank. In her mind, she believed this amount would be sufficient to find a cure for them. The figure, substantial for its time, might seem naive to professionals in the biopharma industry today. Eager to find solutions, she reached out to various laboratories that had limited data on the condition. However, when she introduced herself as a mother with two boys diagnosed with Duchenne, she was often turned away.  The birth of a gene therapy Today, DMD patients have been given new hope. The U.S. Food and Drug Administration (FDA) has approved Elevidys, the first gene therapy for DMD, for patients with the disease between the ages of 4 and 5 years old. This newly approved gene therapy delivers a copy of a gene that encodes a shortened, functional form of dystrophin, the gene that is mutated in DMD patients. Dystrophin is like a shock absorber for muscles, and without it, muscle deteriorates. What can others do to further rare disease research? For those seeking to advocate for a cause, a key strategy is to actively engage with congressional representatives, whether in the United States or elsewhere. It's advisable to frequently contact the offices of Senators or Congress people, introducing oneself and expressing what is important to them. This shouldn't be a one-time conversation but rather a consistent dialogue, akin to building a relationship. LINKS AND RESOURCES MENTIONED Parent Project Muscular Dystrophy https://www.parentprojectmd.org/ PPMD's Decode Duchenne Genetic Testing Program https://www.parentprojectmd.org/about-duchenne/decode-duchenne/ Dante Labs https://us.dantelabs.com/ CONNECT WITH EFFIE PARKS Website https://effieparks.com/ Twitter https://twitter.com/OnceUponAGene Instagram https://www.instagram.com/onceuponagene.podcast/?hl=en LinkedIn https://www.linkedin.com/in/effie-parks-741013164/

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.28.534519v1?rss=1 Authors: Peysson, A., Zariohi, N., Gendrel, M., Chambert-Loir, A., Frebault, N., Andrini, O., Boulin, T. Abstract: The plasma membrane of excitable cells is highly structured and molecular scaffolds recruit proteins to specific membrane compartments. Here, we show that potassium channels and proteins belonging to the dystrophin-associated protein complex define multiple types of planar-polarized membrane compartments at the surface of C. elegans muscle cells. Surprisingly, conserved planar cell polarity proteins are not required for this process. However, we implicate a Wnt signaling module involving the Wnt ligand EGL-20, the Wnt receptor CAM-1, and the intracellular effector DSH-1/disheveled in the formation of this cell polarity pattern. Moreover, using time-resolved and tissue-specific protein degradation, we demonstrate that muscle cell polarity is a dynamic state, requiring continued presence of DSH-1 throughout post-embryonic life. Our results reveal the intricate, highly reproducible, and entirely unsuspected complexity of the worm's sarcolemma. This novel case of planar cell polarity in a tractable genetic model organism may provide valuable insight into the molecular and cellular mechanisms that regulate cellular organization, allowing specific functions to be compartmentalized within distinct plasma membrane domains. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.22.533752v1?rss=1 Authors: Dennis, C., Pouchin, P., Richard, G., Mirouse, V. Abstract: The basement membrane (BM) is an essential structural element of tissues, and its diversification participates in organ morphogenesis. However, the traffic routes associated with BM formation and the mechanistic modulations explaining its diversification are still poorly understood. Drosophila melanogaster follicular epithelium relies on a BM composed of oriented BM fibrils and a more homogenous matrix. Here, we determined the specific molecular identity and cell exit sites of BM protein secretory routes. First, we found that Rab10 and Rab8 define two parallel routes for BM protein secretion. When both routes were abolished, BM production was fully blocked; however, genetic interactions revealed that these two routes competed. Rab10 promoted lateral and planar-polarized secretion, whereas Rab8 promoted basal secretion, leading to the formation of BM fibrils and homogenous BM, respectively. We also found that the dystrophin-associated protein complex (DAPC) associated with Rab10 and both were present in a planar-polarized tubular compartment containing BM proteins. DAPC was essential for fibril formation and sufficient to reorient secretion towards the Rab10 route. Moreover, we identified a dual function for the exocyst complex in this context. First, the Exo70 subunit directly interacted with dystrophin to limit its planar polarization. Second, the exocyst complex was also required for the Rab8 route. Altogether, these results highlight important mechanistic aspects of BM protein secretion and illustrate how BM diversity can emerge from the spatial control of distinct traffic routes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.10.334763v1?rss=1 Authors: Niu, X., Menhart, N. Abstract: Exon skipping is a disease modifying therapy that operates at the RNA level. In this strategy, oligonucleotide analog drugs are used to specifically mask specific exons and prevent them from inclusion in the mature mRNA. Of course, this also results in loss of the corresponding region from the cognate protein, which is one possible therapeutic aim. Exon skipping can also be used to restore protein expression in cases where a genetic frameshift mutation has occurred, and this how it is applied to Duchenne muscular dystrophy, DMD. DMD most commonly arises as a result of large exonic deletions that juxtapose flanking exons of incompatible reading frame in the dystrophin gene, creating a frameshift and abolishing protein expression. Loss of dystrophin protein leads to the pathology of the disease, which is severe, causing death generally in the second or third decade of life. Here, the primary aim of exon skipping is the restoration of the reading frame by skipping an exon adjacent to the patient's original defect. However, the therapeutically expressed protein is of course edited, and missing both the region of the underlying genetic defect, as well as the therapeutically skipped exon. While restoring some protein expression is good, how removing some region from the middle of a protein effects its structure and function is unclear. Complicating this in the case of DMD is the fact that the dystrophin gene is very large, containing 79 exons. Many different underlying deletions are known, and exon skipping can be applied in many ways. It has previously been shown that many exon-skip edits result in structural perturbations of varying degrees. What has been unclear is whether and how exon editing can be done to minimize these perturbations. In this study we examine a systematic and comprehensive panel of possible exon edits in a region of the dystrophin protein, and identify for the first time, exon edits that appear to maintain structural stability similar to wildtype protein. We also identify factors that appear to be correlated with the degree of structural perturbation, such as the number of cooperative protein domains, as well as how the underlying exon structure interacts with the protein domain structure. Copy rights belong to original authors. Visit the link for more info

„Mein Sohn sitzt neben dem Fußballfeld und blickt voller Sehnsucht auf das Spielfeld, wo seine Kameraden hinter dem Ball herjagen. Er würde auch so gerne rennen, dribbeln und Tore schießen! Aber seine Krankheit macht das unmöglich!“ Was die junge Mutter Anna B. hier beschreibt, ist leider in einigen Familien bittere Realität: Der Junge leidet an der lebensbedrohlichen Erb- krankheit Duchenne-Muskeldystrophie (DMD), die zu einem fortschreitenden Abbau der Muskeln führt. Da einmal zugrunde gegangene Muskeln nicht wieder repariert werden können, ist die Früherkennung der DMD umso wichtiger. Nur frühzeitig einsetzende Maßnahmen können helfen, dem Muskelabbau zuvorzukommen und somit das Fort- schreiten der Erkrankung zu verlangsamen. Mit der Kampagne „Hinterher statt voll dabei?“ unterstützt PTC Therapeutics Germany GmbH den Welt-Duchenne-Tag und möchte das Bewusstsein für die DMD in der Öffentlichkeit schärfen. Auch die Website www.hinterherstattvolldabei.de informiert über die Früherkennung dieser seltenenErkrankung − für bessere Chancen der kleinen Patienten. Die Erbkrankheit Duchenne-Muskeldystrophie (DMD) tritt bei etwa 1 von 3.600 bis 6.000 männlichen Neugeborenen auf, in den allermeisten Fällen sind Jungen betroffen.1-5 Erste Anzeichen einer DMD können bereits im Kleinkindalter auftreten. Den betroffenen Kindern fehlt ein funktionsfähiges Muskeleiweiß namens „Dystrophin“. Ohne dieses Eiweiß kommt es zu einem Abbau zunächst der Bewegungsmuskulatur, später auch der Atem- und Herzmuskulatur. Die Muskelschwäche nimmt im Laufe der Zeit zu und breitet sich im ganzen Körper aus. Ein zentrales Ereignis für die weitere Prognose der DMD ist der Verlust der Gehfähigkeit: Wenn es gelingt, die Gehfähigkeit so lange wie möglich zu erhalten, kann hierdurch oftmals das Fortschreiten der Erkrankung verzögert werden. Daher ist das frühe Erkennen der DMD essenziell: Durch frühzeitig einsetzende Maßnahmen besteht die Chance, den Symptomen entgegenzuwirken und den Krankheitsverlauf zu verlangsamen. Lesen Sie den gesamten Beitrag auf MEDIZIN ASPEKTE Die Duchenne-Muskeldystrophie (DMD) ist eine seltene und tödlich verlaufende genetische Krankheit, die überwiegend Jungen und Männer betrifft. Sie führt ab der frühen Kindheit zu einer fortschreitend verlaufenden Muskelschwäche. Die Patienten sterben meist vorzeitig im dritten Lebensjahrzehnt. Die DMD wird durch einen Mangel des funktionellen Proteins Dystrophin verursacht. Dystrophin ist für die strukturelle Stabilität der gesamten Muskulatur, einschließlich der Skelett-, Zwerchfell- und Herzmus- kulatur, überaus wichtig. Patienten mit DMD können schon im Alter von 8-10 Jahren ihre Gehfähigkeit und später die Beweglichkeit ihrer Arme verlieren. Ab dem späten Jugendalter werden DMD-Patienten zunehmend beatmungspflichtig und leiden an lebensbedrohlichen Lungen- und Herzkomplikationen. Mehr Informationen über Duchenne-Muskeldystrophie unter www.hinterherstattvolldabei.de. PTC Therapeutics Germany GmbH - Hinterher statt voll dabei? Weitere Informationen auf MEDIZIN ASPEKTE

Aaand we’re back! Season 4 is coming in hot with some great guests and some more interesting formats. I have some special episodes coming up like the meat-eating heroes panel that we filmed for Food Lies with Mark Sisson, Dr. Shawn Baker, and Dr. Paul Saladino. I also put together a compilation episode that is 6 months in the making with amazing stories from people around America using nutrient dense diets to change their life. What is a nutrient dense diet you may be asking and who am I? The podcast is growing by the day and I want to give new listeners a quick overview. If you’re not new, be sure to stick around there’s a special event announcement at the end. I’m Brian Sanders and I’m creating the feature-length documentary Food Lies which covers the entire story on what humans should be eating including an evolutionary history, where we wrong in the last 60 years, and how we can do this sustainably. We’re in the process of editing now and are shooting some of the last segments in Canada in July. We don’t have a release date yet unfortunately. After years of studying different diets and eating strategies, I’ve landed on what we’re calling the Sapien diet or way of eating or lifestyle. Because it's not a diet - it’s a nutrient dense way to eat for life. I believe you can even dip into non-ideal foods on the weekends or at a special event once you hit your goal weight and if it doesn’t interfere with food intolerances or restrictions. The Sapien diet is based on 3 simple pillars. 1) Nutrient dense whole foods. THis means mostly animal foods which are the most nutrient dense and have the most bioavailable nutrients. This means eating nose to tail and including foods like liver, bone marrow or broth, grass fed butter or tallow, eggs, cold water fish like salmon and sardines, oysters and other mollusks, fermented vegetables, and low sugar fruits like avocados and olives. 2) is for each meal focus on protein, embrace fat, and minimize carbs. The animal protein should be the base of each meal but make sure it comes with enough fat and don’t be scared of it. Most carbs are nutrient poor and really don't provide much to you other than getting in the way of your body burning the fat from your meal or better yet, from your body. And the last pillar is 3) don’t eat all the time. You could call this a condensed eating window or intermittent fasting. Try to eat within an 8-10 hour window each day and let your body rest from constantly having to digest food. There’s a lot more to this so please listen back from episode 1, check out http://sapien.org/diet that’s sapien.org/diet, and we’ll continue to put out more details on the Sapien framework in the future. Ok so onto this episode - I’m starting off the new season with a bang. Maybe you haven't heard of Keith Baar? You should have. I hope to get some of these researchers doing groundbreaking and valuable work into the spotlight Keith is a brilliant researcher who has done great work in his career and published a ton of papers. Much of this work around mTor, muscle protein synthesis (AKA building muscle), collagen synthesis (AKA building all the other tissues that are so important in your body), and so much more. He’s a professor of Molecular Exercise Physiology at UC Davis and works in the Department of Neurobiology, Physiology and Behavior, College of Biological Sciences and the Department of Physiology and Membrane Biology, School of Medicine. He has a bachelors degree in Kinesiology from the University of Michigan, a masters in Human Biodynamics from UC Berkeley, and a PhD in Physiology and Biophysics from the University of Illinois. You’ll learn a ton about how to live long and live strong. He only goes to the gym for 10-12 minutes two times per week yet is still getting stronger each year. We talk about how to live a long healthy life and if eating too much meat is going to help or hurt that. I love talking about the benefits of eating meat so much that I started a grass fed meat company called Nose to Tail which can be found at http://NoseToTail.org We ship nutrient dense boxes of meat to all 48 contiguous US states. We have ground beef with liver, kidney, heart, and spleen mixed in so you get all the nutrients and none of the hassle and barely any of the livery taste. We have so many other things like bone broth, marrow bones, tallow, suet, and all the normal cuts as well. You can also support my work at http://Patreon.com/peakhuman This is where we keep the podcast ad-free so I don’t have to take anyone else’s money to talk about (or be influenced by) their products. This is also where you get the amazing extended show notes put together by Kristi with all the studies and further details included. This is valuable stuff. I’d say better than most nutrition colleges. Definitely better than most nutrition programs teaching all this whole grain nonsense actually. And of course the Food Lies film is still on Indiegogo and needs support. We’re desperately trying to finish it. Check out the “EAT MEAT” shirts there - they are a great way to let people know they can’t blame the steak for what the fries did. One more big thing! We’re having some incredible events in Toronto on Saturday, July 13th and Friday July 19th. We’ll be having a Food Lies special supporters luncheon at North America’s only meat sommelier’s restaurant Speducci. That’s right - he’s a meat sommelier. They will be serving all you can eat platters of their famous cured meats, Speducci meat kabobs, as well as lamb chops, cheeses, and wine. This is going to be a tremendous event with special guests of honor Mikhaila Peterson (peak human episode 18), Tara Couture from SlowDownFarmstead on Instagram (peak human episode 26), and sustainable farmer and speaker Bryan Gilvesy, who will each say a few words I’ll be there with some of the Food Lies and Sapien team as well. Would love to see all you beautiful people in Toronto! Get your tickets on http://NoseToTail.org/event We’ll have another casual one of these in San Diego on July 25th and comment on this podcast post on Instagram if you would like to have an event in your city. Thanks everyone, here’s Keith Baar, PhD.   BUY THE MEAT NosetoTail.org Preorder Food Lies: http://indiegogo.com/projects/food-lies-post Support me on Patreon! http://patreon.com/peakhuman   SHOW NOTES Keith got into research because he wanted to know how muscles get bigger and stronger at a molecular level His PhD looked at which genes are turned on in response to resistance training Why different athletes respond differently to identical training protocols Responders vs non-responders (for muscle growth) Why lifting to failure is the best way to increase muscle mass If you want a strong muscle you just need to lift heavy If you want a bigger muscle you just need to lift to failure Research in people getting same muscle growth lifting 90% of their max for less reps vs lifting 30% of max for more reps and how this could be important to protect against injury One set to failure is just as good as multiple sets Using isolated exercises in combination with compound exercises Keith’s workout routine Lifting every day, whole-body workouts, and “bro-splits” Leucine rich protein and foods leucine is found in Leucine in plants is not as bioavailable Muscle strength is correlated with longevity There are physical, sociological, and metabolic components to why entering old age with muscle mass and strength is associated with living longer The role of mTOR in muscle building and cell growth The difference between using rapamycin and diet to reduce mTOR activity Why it’s important to cycle in and out of mTOR activation once we have reached mature development Calorie restriction and longevity Research Keith was involved in showing the ketogenic diet extended lifespan in mice to the same extent of rapamycin without inhibiting mTOR globally in the body Three ways to activate mTOR and the overlap between resistance training and insulin/IGF-1 pathway We need mTOR to for the immune system, learning and memory, building muscle. and many more important processes in the body Why you don’t need carbohydrates and a spike in insulin to gain muscle Why we need more protein as we age Functional proteins (i.e. bioavailable protein sources) Collagen supplements and what collagen’s role is in the body You need vitamin C in order to synthesize collagen Why fat-adapted athletes may not be able to sprint as well but can outperform in endurance events How fat-adaptation shuts down the ability to properly use glucose for fuel Dystrophin and its importance in maintaining muscle mass as we age Study using natural chocolate (rich is epicatechins) to increase dystrophin and muscle function in elderly Where you can find Dr. Keith Baar: Twitter: @musclescience Learn more about his research here: http://fmblab.com/   BUY THE MEAT NosetoTail.org Support me on Patreon! http://patreon.com/peakhuman   Preorder the film here: http://indiegogo.com/projects/food-lies-post   Film site: http://FoodLies.org YouTube: https://www.youtube.com/c/FoodLies Sapien Movement: http://SapienMovement.com   Follow along: http://twitter.com/FoodLiesOrg http://instagram.com/food.lies http://facebook.com/FoodLiesOrg   Theme music by https://kylewardmusic.com/

Sarepta took a hit from their latest Micro-Dystrophin gene therapy trial update despite showing robust expression in all 4 patients, confirmed by protein analyses and behavioral improvements. In this video, I go through the details of muscular dystrophy, the current treatment options and how this new therapy could significantly improve patients outcomes.I have not taken a position and this is not investment advice. Follow me @matthewlepoire www.breakingbiotech.comRelevant links: https://www.sarepta.com/our-pipeline https://www.sec.gov/Archives/edgar/data/873303/000119312518292068/d616670dex992.htm

Dr. Keith Baar joins Ken and Dawn today for the second of his two-part interview for STEM-Talk. Keith is a renowned scientist in the emerging field of molecular exercise physiology who has made fundamental discoveries on how muscles grow bigger, stronger, and more fatigue resistant. He is the head of the Functional Molecular Biology Laboratory in the Department of Neurobiology, Physiology, and Behavior at the University of California, Davis. In his lab, he leads a team of researchers attempting to develop ways to improve muscle, tendon and ligament function. Part one of our interview, episode 62, covered Keith’s childhood in Canada and his undergrad years at the University of Michigan as well as his time at the University of California, Berkeley, where he earned a master’s degree in human biophysics. We talked about Keith’s work at the University of Illinois, where he received a doctorate in physiology and biophysics. We also covered Keith’s time in the lab of John Holloszy, who is known as the father of exercise research in the United States, as well as the five years Keith spent at the University of Dundee in Scotland. Episode 63 picks up with Keith explaining his decision to return to the states and join the faculty at the University of California, Davis.  Ken and Dawn then talk to Keith about his most recent research, some of which is looking at how to determine the best way to train, as well as what types of foods compliment training to decrease tendon and ligament injury and accelerate return to play. This work has the potential to improve muscle function not only in athletes, but also improve people’s quality of life as they age. Another key topic covered in part two of our interview is the research Keith is doing on a ketogenic diet and its potential to reduce cancer rates and improve cognition. Keith also provides his thoughts on what optimal workouts and nutrition should look like. Links: Baar’s UC Davis physiology department bio: https://www.ucdmc.ucdavis.edu/physiology/faculty/baar.html Baar’s UC Davis biology department bio: https://biology.ucdavis.edu/people/keith-baar Functional Molecular Biology Lab website: http://www.fmblab.com/  Molecular brakes regulating mTORC1 activation in skeletal muscle paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137116/ Age-related Differences in Dystrophin article: https://www.ncbi.nlm.nih.gov/pubmed/27382038 Show notes: 2:54: Dawn begins part 2 of our interview by mentioning that for the past eight years, Keith has been working at the University of California Davis. She asks Keith what prompted him to return to the U.S. from Scotland and join the faculty at UC Davis. 3:37: Dawn points out that Keith’s Functional Molecular Biology Lab conducts research across a range of related topics, including musculoskeletal development and adaptation as well as methods for engineering functional musculoskeletal tissues in vitro. She asks Keith to give a high-level overview of some of that research. 4:16: Dawn comments that some of Keith’s recent work has shown that we can use specific nutrition and training strategies to optimize injury recovery and prevention. She goes on to say that musculoskeletal injuries are among the most common problems that active people have. 8:45: Ken talks about how Keith has noted that tendon stiffness is dependent upon collagen content, and the amount of crosslinks within. He goes on to mention that Keith has developed various training modalities, as well as nutritional protocols, that can increase and decrease tendon stiffness. Ken begins this line of inquiry by asking about the training methods for this purpose. 12:04: Following up on the previous question, Ken asks whether anyone has looked at how blood flow restriction training, which is increasing in popularity, affects tendon stiffness. 13:32: Dawn moves on to asking about nutrition. She mentions that Keith’s lab has done a great deal of...

Today’s episode is the first of a two-part interview with Dr. Keith Baar, the head of the Functional Molecular Biology Laboratory in the Department of Neurobiology, Physiology, and Behavior at the University of California, Davis. In his capacity as a researcher, Keith has made fundamental discoveries on how muscle grows bigger, stronger, and more fatigue resistant. He is a renowned scientist in the emerging field of molecular exercise physiology, and is leading a team of researchers attempting to develop ways to improve muscle, tendon and ligament function. Part one of our interview features our conversation with Keith about his background and his time time in the lab of John Holloszy, who is known as the father of exercise research in the United States. Episode 63 of STEM-Talk has Dawn and Ken talking to Keith about his most recent research, which is looking at how to determine the best way to train, as well as what types of foods compliment training to decrease tendon and ligament injury and accelerate return to play. This work has the potential to improve muscle function and people’s quality of life, especially as they age. Ken and Dawn also have a conversation with Keith about the research he is doing on a ketogenic diet and its potential to reduce cancer rates and improve cognition. Links: UC Davis physiology department bio: https://www.ucdmc.ucdavis.edu/physiology/faculty/baar.html UC Davis biology department bio” https://biology.ucdavis.edu/people/keith-baar Functional Molecular Biology Lab website: http://www.fmblab.com Molecular brakes regulating mTORC1 activation in skeletal muscle paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137116/ Age-related Differences in Dystrophin article: https://www.ncbi.nlm.nih.gov/pubmed/27382038  Show notes: 3:14: Dawn opens the interview by mentioning that Keith grew up in Canada, and asks what he was like as a child. 4:02: Dawn asks if Keith was interested in science as a kid. 4:53: Dawn comments that after high school, Keith came to the U.S. to attend the University of Michigan, where he earned a bachelor’s degree in kinesiology. She Keith if Michigan was where he first became interested in the science of how muscles work. 7:54: Dawn asks Keith if he played any sports at Michigan. 8:34: Dawn asks what lead Keith to attend the University of California, Berkeley to pursue a master’s degree in human biophysics. 9:39: Dawn mentions that after his time at Berkeley, Keith returned to the Midwest to attend the University of Illinois where he received his doctorate in physiology and biophysics. She asks why he decided on Illinois for his doctoral work. 11:12: Ken mentions that Keith’s Ph.D. work focused on the effect of resistance exercise on specific molecular markers that are related to muscle growth. He goes on to say that Keith identified that mTOR complex 1 was activated in response to resistance exercise and that the activation was proportional to the load across the muscle. He asks Keith to talk about this work and its significance. 16:20: Ken comments how surprising that discovery must have been. 17:33: Ken asks Keith to explain the two basic ways of activating mTORC1 in skeletal muscle. Ken also asks whether these two are merely additive, or if together they elicit a greater muscle protein response than either would independently. 29:49: Dawn mentions that after Illinois, Keith went to work in the lab of John Holloszy at Washington University in St. Louis, a professor of medicine who is known as the father of exercise research in the United States. Dawn asks if is Holloszy is the one who discovered that when people do endurance exercise that their muscles accumulate more mitochondria. 32:24: Ken asks about the role of PGC-1a. 38:43: Ken comments that we know most sports require a combination of strength and endurance for optimal performance, bringing up the topic of concurrent training.

Duchenne Muscular Dystrophy, a rare genetic disease, causes progressive muscle wasting that slowly robs people of abilities and leads to death. In recent years, much attention has focused on the use of antisense oligonucleotides to bypass defective portions of the exon that codes for the dystrophin gene to restore its production. Dystrophin is a protein that is essential to healthy muscle. Summit Therapeutics is taking a different approach. Instead of restoring dystrophin, Summit is developing a drug that activate utrophin, a related protein that serves a similar function to dystrophin during fetal development, but then shuts off. We spoke to Glyn Edwards, CEO of Summit, about the company’s utrophin activator ezutromid, its licensing deal with Sarepta Therapeutics, and why, unlike the exon-skipping drugs that target specific subpopulaitons of Duchenne patients, ezutromid could provide benefits to patients broadly.

Guest Host: Scott Harper, PhD, is a principal investigator in the Center for Gene Therapy in The Research Institute at Nationwide Children’s Hospital. Guest: Kevin Flanigan, MD, principal investigator in the Center for Gene Therapy, is also an attending neurologist at Nationwide Children’s and professor of Pediatrics and Neurology at The Ohio State University College of Medicine. View the published abstract for this month’s featured research article. Learn more about the Flanigan Lab and their research.

Guest Host: Scott Harper, PhD, is a principal investigator in the Center for Gene Therapy in The Research Institute at Nationwide Children’s Hospital. Guest: Kevin Flanigan, MD, principal investigator in the Center for Gene Therapy, is also an attending neurologist at Nationwide Children’s and professor of Pediatrics and Neurology at The Ohio State University College of Medicine. View the published abstract for this month’s featured research article. Learn more about the Flanigan Lab and their research.

Dr. James Ervasti Discusses Stability of Therapeutic Forms of Dystrophin :: January 2013 Guest: Dr. James Ervasti, PhD, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Access an abstract of this month’s featured research article: Hum Mol Genet. 2011 Aug 1;20(15):2955-63. doi: 10.1093/hmg/ddr199. Epub 2011 May 10.

Dr. James Ervasti Discusses Stability of Therapeutic Forms of Dystrophin :: January 2013 Guest: Dr. James Ervasti, PhD, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Access an abstract of this month’s featured research article: Hum Mol Genet. 2011 Aug 1;20(15):2955-63. doi: 10.1093/hmg/ddr199. Epub 2011 May 10.

Dr. Federica Montanaro Discusses New Cardiac Dystrophin Associated Proteins :: December 2012 Guest: Dr. Federica Montanaro, PhD, principal investigator in the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital Access an abstract of this month’s featured research article: Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins. PLoS One. 2012;7(8):e43515.

Dr. Federica Montanaro Discusses New Cardiac Dystrophin Associated Proteins :: December 2012 Guest: Dr. Federica Montanaro, PhD, principal investigator in the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital Access an abstract of this month’s featured research article: Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins. PLoS One. 2012;7(8):e43515.

Drugs that reduce microtubule density or prevent the production of reactive oxygen species in skeletal muscle might slow the progression of Duchenne muscular dystrophy.

Guest: Professor Steve Wilton, Australian Neuromuscular Research Institute, The University of Western Australia Access an abstract of this month’s featured research article: Dystrophin isoform induction in vivo by antisense-mediated alternative splicing. Mol Ther. 2010 Jun;18(6):1218-23.

Guest: Professor Steve Wilton, Australian Neuromuscular Research Institute, The University of Western Australia Access an abstract of this month’s featured research article: Dystrophin isoform induction in vivo by antisense-mediated alternative splicing. Mol Ther. 2010 Jun;18(6):1218-23.

Guest: Jerry Mendell, MD, Nationwide Children's Hospital Access an abstract of this Month's Featured Research Article: Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med. 2010 Oct 7;363(15):1429-37.

Guest: Jerry Mendell, MD, Nationwide Children's Hospital Access an abstract of this Month's Featured Research Article: Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med. 2010 Oct 7;363(15):1429-37.

A physiologist studies how we sense mechanical stimulation

Kay Davies discusses her research of genetic diseases such as Duchenne Muscular Dystrophy, problems which limit the development of therapy and the need for effective treatment and screening processes.

We report on multicolor fluorescence in situ hybridization protocols for the simultaneous visualization of deletion-prone regions for carrier detection of Duchenne/ Becker (DMD/BMD) muscular dystrophy. Cosmid and yeast artificial chromosome (YAC) clones specific for preferentially deleted subregions of the dystrophin gene were labeled differentially and detected with three different fluorochromes using digital imaging microscopy. This approach allows for an assessment of the carrier status of female relatives even in families where no index patient is available. Cosmid and YAC clones, and different probe-generation protocols are compared with respect to their feasibility for carrier detection. The use of histone-depleted interphase nuclei (Halo-preparations) for deletion mapping is demonstrated and shown to have a resolution power of 5 kb.