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RealTalk MS
Episode 451: Meet the 2026 Winner of the John Dystel Prize for MS Research with Dr. Ludwig Kappos
00:32:34
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I'm john strum, and this is real talk, mississippi. It's April 21st, and we have a lot to talk about. The annual meeting of the American Academy of Neurology is underway in Chicago this week, and one of the highlights of the meeting is the presentation of the John Distel Prize for Research in Multiple Sclerosis, which is awarded jointly by the National Ms. Society and the American Academy of Neurology. The $40,000 prize recognizes outstanding contributions to research that have led to breakthroughs in the understanding, prevention, treatment, or cure of multiple sclerosis. This year's winner of the distal prize is Dr. Ludwig Kappos, a physician scientist at the University Hospital Basel in Basel, Switzerland, and the director of the Research center for Clinical Neuroimmunology and neuroscience, Basel. Dr. Bruce Bebo, the Ms. Society's chief research and medical affairs officer, described Dr. Kappos is, and I'm quoting now, one of the most influential leaders in modern Ms. Research. His work has helped shape how we design clinical trials, evaluate new therapies, and ultimately care for people living with Ms. Few individuals have had such a broad and lasting impact on the field. End Quote Dr. Kappos has played a major role in how clinical trials in Ms. Are conducted. He helped establish the Expanded Disability status scale, or EDSs, which is the gold standard for measuring disability in people with Ms. And he and his team have advanced our current understanding of a key driver of disability in Ms. Known as progression independent of relapse activity, or PERA. Dr. Kappos will be delivering the Distel Prize Lecture at the American Academy of Neurology meeting this week, and he'll be joining us today with a preview of that lecture and a conversation you won't want to miss. But before we get to my conversation with Dr. Ludwig Kappos, there are a few other things that you should know about. For the longest time, it was believed that someone living with the most common form of Ms. Relapsing remitting Ms. While experts believe their Ms. Was stable unless or until they experienced a relapse, today we know more and we know better. Progression independent of relapse activity, or pera, means that for someone living with relapsing remitting ms, disease progression, neurodegeneration is taking place even when that individual isn't experiencing a relapse. And that means that monitoring disease activity between relapses becomes even more important. One way to do that is by measuring neurofilament light chain levels in the bloodstream. Neurofilament light chain, known as NFL, is a protein that's released into the bloodstream when there's nerve cell damage in the central nervous system, making it a biomarker for that nerve damage. And last week, a blood test developed by Roche that measures NFL levels and delivers results in just minutes was approved to be marketed for use throughout the European Union. Because this test requires just a simple blood sample, it can be used along with other monitoring tools to monitor Ms. Disease activity more frequently. And that monitoring, providing a real time understanding of disease activity, can help guide and support treatment decisions. In the United States, Roche's NFL blood test has been granted Breakthrough Device Designation by the fda, and we'll keep you posted on further news about this tool that makes monitoring Ms. Disease activity easier, accessible and convenient. Newly published results from a real world study of mothers with Ms. Show that using most disease modifying therapies shortly before or during pregnancy does not increase the risk of neurodevelopmental birth defects or birth defects which affect the development and function of the brain. However, there is a category of DMTs called S1P receptor modulators and this would include Gilenia, Mayzent and Pomvory. They were linked to an increased risk of major birth defects. In this study, an Israeli research team analyzed the medical records of all the children who were born to mothers with Ms. Between 2005 and 2023 in the cloud health services in Israel. Of the 1374 children included in the study, 890 had not been exposed to any disease modifying treatments before birth and 484 were exposed to one or more DMTs at some point between six months before conception and their birth. Among these 484 children who were exposed to a DMT, almost half were exposed to an interferon based therapy. The balance were exposed to Tecfidera, Ocrevus, Baffertam, Gilenia, Mazant and Pomvoury. Over an average of six and a quarter years, 297 of these children were diagnosed with a neurodevelopmental disorder including autism, emotional disturbance and developmental issues that affected speech, language or coordination. However, after adjusting for other factors that could contribute to neurodevelopmental disorder like the mother's age and socioeconomic status, and accounting for exposure only during the mother's pregnancy, the researchers did not find a significant association between disease modifying therapies and a higher risk of developing neurodevelopmental disorders. Now, those children who were exposed to Gilenia, Mezent or Ponvery during the mother's pregnancy did demonstrate a higher risk of major congenital anomalies, but it's important to note that this was a tiny statistical sample, so it's a more imprecise conclusion. It's also important to point out that these S1P receptor modulators aren't prescribed to women who are planning getting pregnant. If you'd like to review the details of this study, you'll find a link in today's show. Notes. And if you'd like to hear more about family planning, pregnancy and the postpartum phase for women with MS, you'll want to catch our upcoming episode on May 5th, when my guest will be one of the foremost authorities in the world on women's health issues and Ms. Dr. Riley Bovet. Animals like yaks and Tibetan antelope that live on the Tibetan Plateau with an average elevation of 14,700ft carry a gene mutation known as Retsat, and scientists have long believed that this gene mutation allows the animals to maintain healthy brain function despite living in a chronically low oxygen environment. So what might yaks and Tibetan antelope have to do with ms? Stay with me A Chinese research team wanted to determine whether this same gene mutation could protect the myelin sheath. Just a quick reminder, in ms, the myelin sheath that protects nerve cells becomes damaged, and that's what leads to Ms. Related disability. So the researchers exposed newborn mice to low oxygen conditions similar to altitudes above 13,000ft. For about a week, the mice carrying the RETSAT gene mutation outperformed those without it in tests that measured learning, memory and social behavior. Their brains also showed higher levels of myelin around nerve fibers. The researchers then explored whether the mutation could help repair existing myelin damage that was similar to the damage that occurs in Ms. In mice with the mutation, damaged myelin recovered more quickly and more completely. The affected areas also contained greater numbers of mature oligodendrocytes. It's a big word for the cells that are responsible for producing myelin. The researchers further discovered that the mice with the RETSAT gene mutation produced increased levels of a metabolite called ATDR in their brains. These metabolites support the growth and maturity of oligodendrocytes, which in turn help rebuild the myelin sheath. When researchers administered ATDR to mice with the mouse version of ms, the mice showed reduced disease severity and improved motor function. Since ATDR is something that everyone already has in their body, this discovery could point to a new pathway for neuroprotection or even remyelination therapies. Stay tuned for further developments and in the meantime, if you'd like to review the details of this study, you'll find that link in today's show. Notes. If you ask an Ms. Specialist to define high quality Ms. Care, they would probably say effective treatments and faster diagnosis. If you pose the same question to someone living with ms, you might get a different response. A research team interviewed 42 people including 13 Ms. Specialists, 11 non Ms. Specialists, 9 clinical educators and 9 people living with Ms. Asking questions about what constitutes the highest quality of Ms. Care. Everyone interviewed agreed that several areas of Ms. Care were in need of improvement. Healthcare providers and clinical educators indicated that understanding options and monitoring the safety of disease modifying therapies topped the needs improvement list. Along with prescribing more effective treatments, collaborating with other healthcare providers and using up to date diagnostic criteria, people with Ms. Indicated that taking a person centered approach to care that prioritized their preferences, needs and values was at the top of their list. They talked about things like clear communication, active listening, and feeling supported during difficult treatment decisions. Everyone agreed that collaboration is essential. The concept of teamwork was frequently raised and if I was going to synthesize what healthcare providers and people with Ms. Want, I might point out that when a healthcare provider thinks about teamwork, they check to make sure that the patient themselves is part of that care team. When an Ms. Care team includes the patient, things like clear communication, active listening, treatment adherence and more all become automatic. Because the patient is part of every conversation and part of every decision. Their Ms. Care isn't about them, it's with them. This series of interviews was part of the National Ms. Society's Echo Ms. Project, which is a national program designed to help general neurologists and primary care doctors improve their Ms. Expertise and Ms. Care training. If you'd like to review the details of this project, you'll find that link in today's Show Notes. I want to remind you that this episode of Real Talk Ms. Is sponsored by Able now, a tax advantage savings program for people with disabilities. If you're living with multiple sclerosis, this is important news. Expanded federal rules mean more adults with disabilities, including many people with ms, can open an ablenow account. Ablenow lets individuals save and invest money without affecting their eligibility for certain public benefits such as SSI or Medicaid. For many of you, it can be an essential financial tool. To learn more and understand. If you're eligible to open an account, visit ablenow.com and you'll find that link in today's show notes when I think of how much has changed when it comes to delivering high quality care to people living with Ms. I think of the decades of contributions that have been made by my guest, this year's winner of the John distel prize for Ms. Research, Dr. Ludwig Kappos. In a moment we'll meet Dr. Kappos. My guest, Dr. Ludwig Kappos is a physicist, physician, scientist at the University Hospital Basel in Switzerland where he serves as director of the Research center for Clinical Neuroimmunology and neuroscience, Basel. Dr. Kappos has played a central role in advancing Ms. Research and treatment over the past several decades and he is this year's winner of the John Distel Prize for Multiple Sclerosis Research. Welcome to the podcast, Dr. Capos, and congratulations on being named the 2026 Distal Prize winner.
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Hi Jon, and thank you for your congratulations. Perhaps an initial remark I take it, and I'm happy about this award, but I'm also very well aware that everything that we have accomplished in the area of ms, of clinical Ms. Research was a group effort. So I'm here and then receiving the award at the Academy in the name of many, many collaborators, not only in Switzerland, but internationally.
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Well, I think I should at least remind my listeners that you've received virtually every major honor in the field, including the Charcot Award just last year. Looking back at your career, which of your contributions do you feel has had the most direct impact on the day to day lives of people living with ms?
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Well, certainly my involvement now over three decades and four decades in the design in leading clinical trials, more and more systematic and advanced methodology clinical trials that have led to the approval of nearly all of the available disease modifying drugs for multiple scleros. This was a very personally very rewarding journey and I think has really contributed to improving the prognosis, the life, expense life, say expectation of people with multiple sclerosis not on around the world.
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A
I think I'd like to start virtually at the beginning. You've been involved in this work since the mid-1980s, I believe, long before we had the 20 plus disease modifying therapies that we have today. What was it about the Ms. Puzzle that drew you in the beginning during those early years at the Max Planck Society?
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Well, at the Max Plan Society we were studying the experimental model of multiple sclerosis and my mentor and head of the research group Atmut Wekerle and his group developed specific T cell lines and were able to transfer the disease, experimental disease, only with activated T cells. That was a norm. It's now something everyone knows. But it was a, at this time and then they were also able to find this kind of specific cells and potentially encephalitogenic cells in people with Ms. And also in so called healthy controls. And this was very puzzling. What is the difference? What is in their regulation that gets wrong? And on the other side, the possibility to develop immuno modulating drugs or even immunosuppressive drugs that addressed exactly this pathogenesis. That was the main stimulator in my young days as a neurologist. When I joined the group, as I
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heard you mention a moment ago, you've actually played a pivotal role in the clinical trials for almost every approved Ms. Therapy today. When you look at the leap from the early interferons to modern high efficacy treatments like B cell depleters, what's the most significant lesson you've learned about how we should be designing clinical trials?
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Well, first of all, I learned that it is necessary to accept only partial success and also to try not to be disappointed by either negative trials or trials that to not yield what you would have expected. And this has helped to develop the methodology to learn and to discern or to detect those new compounds that then improved the outcome. I think that's the main lesson and that you should not be satisfied with a result and always seek for a more specific and more effective way of action.
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You were instrumental in clinical trials that finally brought treatment options like Mayzent and Ocrevus to people living with progressive forms of Ms. What do you see as the biggest remaining hurdle in finding that home run for the progressive Ms. Community?
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Yeah, that's of course in the center of the attention of most people involved in the field. And the key question that we need to answer is which kind of paradigm do we need in order to test new compounds? We have been very successful with many new drugs with a relatively simple algorithm that showed if you show an effect on the inflammatory activity on new lesions or relapses, then you can expect with a very high probability to be nearly sure that you have also a clinical effect. But this does not stand for progression. This was the experience with the first compound when we saw little effect on progression with interference and then along the whole journey. So we need another approach, another way to test new therapies in order to select those that then can be taken further. And this was very clearly shown that we definitely need something different in the recent PTK inhibitor studies, especially tolebrutinib, is in my mind, the first really complete and well conducted phase three program that shows that we need to change the paradigm. There is a Drug with perhaps not very high, but still very well reproducible effect on disability progression, but no effect, or at least a very minor effect on acute disease activity. And therefore we cannot use. We need to find something else to test that. And this includes new methods of assessment. And this is the whole change in the field that accepts that the pure clinical assessment is not sufficient, that this can be refined and be more comprehensive. And this is an area where we are very active at the moment with digital measures. But on the other side, that we need to do that together with an assessment that discloses or approaches the biology behind the clinical symptoms and the complaints that people have with the disease. And this is still a work in progress, makes it so interesting also for me to continue trying hard, because we have good approaches, but we need a more systematic way of evaluating these and of course then also implementing in clinical trials. And for that we need also the support of those who are not directly involved in research. So people with Ms. Need to understand that and need also to participate in observational studies that are not so demanding as clinical trials, but still to accept that it makes sense to have an evaluation of the disease also with additional non clinical methods that allows to better understand how it develops and then to find the entries, the windows of opportunity where new treatments can specifically target this pathogenic process.
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A
I want to circle back to that in just a moment, but as we're talking about the concept of progression, you've been a leading voice in defining progression independent of relapse activity or pera. This concept essentially proves that Ms. Can be active and neurodegeneration can be occurring even when there are no visible relapses. How does this shift our understanding of when we should be starting high efficacy treatments?
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B
Well, I think the knowledge or the know them, that we are certain that indeed, even before clinical manifestation, the disease is progressing, asks for something that is at this time perhaps even preventive, preventive of clinical symptoms. And therefore we are urged to apply treatments in the very early phase in order to have this effect. And there are indications, still not a proof, that we really can make a big difference. That there is an advantage is already known by several observational studies. But the definite proof and quantitation of this approach is still lacking. What is reassuring, that there are in the meantime treatments that are quite well tolerated and therefore do not require too much or induce too much of a burden for people with Ms. If they start early. Perhaps even the opposite, if we compare to the adverse events that people experience with the first drugs with injectables like interference.
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If disability is accruing silently in the background, does this mean that the current definition of NEDA or no evidence of disease activity needs serious modification or is perhaps outdated?
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Absolutely, I fully agree with you. It helped to have a comprehensive measure, but it does address sufficiently progression of the disease. It is one part of neda, but it is there. It is based on a very rough assessment that has also served in clinical trials and is accepted the ed. But we need to understand that additional clinical measures that are more granular and more sensitive to change must be implemented. And on the other side, what I already mentioned that we need additional measures that disclose the underlying pathology that may not manifest yet as clinical symptoms, but is still very important for the outcome of the the further development of the disease.
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A
Thinking about clinical assessment, you helped standardize the edss, which is the accepted gold standard for measuring disability. Yet we often hear people living with Ms. Express frustration with how the EDSS fails to capture their lived experience. Do you see digital biomarkers or wearable technology eventually replacing or augmenting the traditional finger to nose neurological exam?
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Yes. I can reassure you that since the beginning of my career I share this frustration. I was following people with Ms. Where the EDSS did not change and on the other side I felt that there is a progression of the disease and they told me so. That's why we are now trying to use something that is affordable, not invasive, and uses the current widespread and widely used technology, including smartphones and smart watches. With smart watches we know that we can assess on a more continuous way certain activities, specifically motor activities. With smartphones we can use the sensors included in order to define small tasks. We call them small challenges. One minute each that can then rather objectively, over time, with five minutes or ten minutes investment every week, or every other week or every month, can document certain parts of our neurological functions. And this is especially interesting and important in areas that are not covered by the neurological examination by a physician. That is especially cognitive functions, where we have seen that with cognitive games that many people do anyway and are quite well accepted are not an interrogation or examination, but a small challenge that with these games we can have a rather good reflection of cognitive function development. Even the learning effects that occur if you repeat that can tell you something about the disease, about the reserve, but also about the state of the disease. And this is something that needs further validation and that's what we are currently validating. Together with other centers.
- [29:35]
A
You'll be delivering the Distel Prize lecture at the American Academy of Neurology annual meeting in Chicago this week. What's the core message you want the global Ms. Community to take home this year?
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Well, the core message is along the lines that we discussed here. I think we need to understand why we have reached this very satisfactory state regarding Ms. Understanding and treatment. But what we need to change and to learn from failures and especially recent failures in order to get this next important challenge. Stopping halting progression and of course in a further step and this methods that we can use are very similar. Improving the state so improvement of clinical symptoms.
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Dr. Ludwig Kappos, I want to thank you for a body of past and current work that continues to improve the lives of everyone living living with Ms. And thanks so much for talking with me today.
- [30:50]
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Thank you, John.
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A
That's going to wrap up this episode of Real Talk Ms. Real Talk, Ms. Is powered by the National Ms. Society and you can share this episode of the podcast by letting your friends or family members know that all they have to do is point their web browser@realtalkms.com 451. You'll find that link in today's show notes so you can easily copy and paste it right into an email or a text. Myelin repair or remyelination carries with it the promise of regaining function that's been lost to Ms. Myelin repair is a natural process in the brain, but for some reason that natural myelin repair stops working for people with Ms. My guest next week, Dr. Larry Sherman, may have identified why that happens and his team is already working on an intervention that returns that ability to repair myelin to people living with Ms. I hope you're planning to join me next week when Dr. Sherman explains how his discovery could turn out to be a game changer. I'm John Strum. Thanks for listening. Stay safe and make healthy choices.
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It.