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A
I'm john strum, and this is real talk, mississippi. It's January 27th, and we have a lot to talk about. Every week on this podcast, we explore the science that's changing the landscape of neuroimmunology. But today, I'm asking for your help in moving that science forward faster. I'm lacing up my sneakers once again for Walk ms, and I'm asking for your support in a very specific mission. Ending multiple sclerosis for good. As many of you know, this is deeply personal to me, and it's a goal I'm committed to seeing through. The National Ms. Society is the largest private funder of Ms. Research in the world. By donating to Walk ms, you're directly fueling the breakthroughs that lead to better treatments and ultimately, a cure. We've never been closer to a world where no one ever has to hear the words, you have Ms. And your support is what bridges that final gap. Whether it's ten dollars or a hundred, every dollar goes toward the mission of putting this disease in the history books. The link to my personal fundraising page is easy. Just visit realtalkms.com walkms. And you'll find that link in today's show. Notes I want to say thank you from the bottom of my heart to each of you who's able to contribute. Thank you for standing with me. Thank you for being part of the generation that finally ends multiple sclerosis. And speaking of ending multiple sclerosis, a couple of weeks ago we talked about a new global research initiative focused on preventing Ms. And for some of you, it may have taken a minute to connect the dots between the idea of preventing Ms. And the goal of ending ms, which, as many of you know, has always been one of the three goals in the Pathways to Cures roadmap. My guest this week is Dr. Bruce Bebo, the National Ms. Society's Executive Vice President and Chief Research and Medical affairs officer. And Bruce is going to walk us through an overview of what preventing multiple sclerosis means and how the experts are hoping to achieve that goal. But before we get to my conversation with Dr. Beebo, there are a few other things that you should know about. Last week, the National Ms. Society announced that Dr. Manuel Frieza is the recipient of the 2025 Barancik Prize for Innovation in Ms. Research. Dr. Frieza is a clinician scientist at the Institute of Neuroimmunology and Multiple Sclerosis of the University Medical Center Hamburg Eppendorf in hamburg, Germany. And Dr. Friesa is being recognized for his groundbreaking work studying the interactions between inflammation and nerve cell death that drives Ms. Disease progression. Just as a quick refresher in ms, the immune system attacks myelin, the protective coating around our nerve cells. As this process of demyelination occurs, nerve cell fibers are damaged. Over time, this nerve cell damage and eventual nerve cell death leads to increased disability and disease progression. Dr. Frieza's research focuses on how nerve cells react to the inflammation caused by Ms. Along with his team, Dr. Friesa discovered that nerve cells aren't just passive victims of attack as had been previously believed. Dr. Fra was able to show that nerve cells actively respond to inflammation by triggering internal pathways that disrupt several processes that nerve cells require to stay healthy. This disruption leads to neurodegeneration, and it's already been shown that drug interventions and even genetic interventions that target these processes can help preserve nerve cell health and in some cases reduced disease severity. In the mouse model of ms, understanding how these interventions can impact these pathways opens the door to potential new treatments that could stop Ms. Progression. Dr. Frieza has also uncovered a new brain immune system connection that reduces Ms. Inflammation. He found that levels of a protein in the bloodstream called GDF15 increase during pregnancy, and this increase in GDF15 levels is associated with fewer Ms. Relapses. GDF15 sends signals to specific neurons in the brain stem that reprogram the immune system. This reprogramming reduces harmful immune cells from entering the brain and spinal cord and protects against inflammation. And the good News is that GDF15 therapies are already being tested in humans and for other conditions. So if and when there are clinical trials testing GDF15 and MS, those trials are going to move along more quickly. Beyond all of his game changing work in the lab, Dr. Frieza continues to treat people with Ms. In the clinic at the University Medical Center, Hamburg, Eppendorf, where he's also overseeing a clinical trial testing the efficacy of CAR T cell therapy for progressive Ms. And as a reminder, if you'd like to get up to speed on CAR T cell therapy for MS, you might want to catch episode number 424 of Real Talk MS, where I talk with the first person with Ms. In the United States to receive this experimental treatment. Next week, Dr. Friesa will deliver the Barancik Prize lecture at the Americas Committee for Treatment and Research in Ms. Forum, better known as the ACTROMS Forum, where I'm looking forward to speaking with him. The National Mississippi Society's Ms. Care Deserts Initiative focuses on addressing critical gaps in Ms. Care in regions across the United States where specialty Ms. Care is limited and the latest step in this initiative is being launched in partnership with the Wisconsin Collaborative for Health Care Quality. Called Bridging the Gap, Reducing Delays in Multiple Sclerosis Diagnosis and Expanding Access to Care in Wisconsin, this initiative is designed to reduce delays in getting an Ms. Diagnosis and expand access to care to the over 14,000 people living with Ms. In Wisconsin. The year long initiative will clearly measure the timeline to an Ms. Diagnosis in Wisconsin, showing the average time from an initial Ms. Related symptom to diagnosis segmented by geography, race and ethnicity and insurance type. The initiative will also pinpoint high priority intervention zones by identifying where delays in getting an Ms. Diagnosis are most severe. It will also create an educational program and digital tools for primary care providers, general neurologists and emergency room clinicians to improve their recognition of early Ms. Symptoms and streamline referral pathways. We'll keep you updated as the Ms. Society launches this and other partnerships and initiatives aimed at improving time to diagnosis and access to quality care. A drug discovery Collaborative research network called BRAVE in ms, established and funded by the International Progressive Ms. Alliance, has discovered that a treatment originally developed for sleep and wakefulness disorders also shows the ability to protect nerve cells and promote myelin repair in experimental models of Ms. The drug is called Bavasant, and if you're into the technical side of things, Bavasant is a histamine receptor H3 antagonist, which means that it's a drug that blocks receptors that are primarily found in the brain and prevents them from inhibiting the release of neurotransmitters. By blocking these receptors, they increase levels of histamine, acetylcholine, dopamine and norepinephrine, which collectively promote wakefulness and improved cognition. The BRAVE and Ms. Collaborative Drug Discovery Network is led by Professor Gianvito Martino of University Vita Salute, San Rafael and scientific Director at IRCCS San Rafaeli Hospital in Milan, Italy. The network involves 13 investigators from Europe, Canada and the United States, including the Paris Brain Institute, University of California, San Francisco and University Hospital Munster. This research network is focused on investigating drugs that have already been approved for other treatments. They've developed an innovative drug screening platform that combines computer analysis with lab grown human cells, brain tissue samples and animal models to identify molecules that may protect nerve cells and or promote myelin repair. And instead of evaluating each molecule individually, investigators can screen thousands of compounds at a time, speeding up the process and leading to potential solutions more quickly and more cost effectively. After reviewing hundreds of molecules already approved for other indications and given its ability to protect nerve cells and promote remyelination, the team has identified Bavasant as a promising candidate for treating progressive Ms. The International Progressive Ms. Alliance has already agreed to fund the BRAVEN Ms. Project with an additional €700,000 to extend their study of Bavasant. So we'll be hearing more about this potential treatment as the research network continues its work. And if you'd like to learn more about this discovery, you'll find a link in today's show. Notes. I've often said that to me, the toughest part of living with Ms. Is the uncertainty of never knowing what lies ahead. One person is diagnosed with Ms. And they experience very few symptoms for someone else. Their Ms. Journey may be quite different. And sometimes I think that just living with the not knowing may be the worst of all the invisible symptoms of Ms. So I'm glad to share that A research team in Italy has been successful at using artificial intelligence to predict whether someone newly diagnosed with Ms. Will experience disability worsening that occurs even in the absence of relapses. Using a type of AI called machine learning, a computer analyzes a person's age at the time of Ms. Onset, how long that person has had ms, and their early disability score to predict which individuals are likely to experience progression independent of relapse activity or pera within the first three years of their diagnosis. Research has shown that most disability progression in Ms. Actually occurs due to this gradual worsening that's happening in the central nervous system even when someone isn't experiencing a relapse. Currently, there's no method to determine whether someone who's been newly diagnosed is likely to experience this progression independent of relapse activity in the first few years following their diagnosis. So the research team used clinical and demographic data from 719 people with Ms. Who underwent routine assessments over the first three years following their diagnosis. After those three years, 13% of the patients had experienced progression independent of relapse activity. So, taking all of the variables that are routinely measured during a clinic visit, the researchers calculated a statistical measure that was applied to a machine learning model, and the results were impressive. Now, the research team has stressed that more research is needed to validate this approach, but I think this may demonstrate that one day in the not too distant future, we'll be able to leave some of the uncertainty surrounding Ms. In the future back in the past. If you'd like to review the details of this study, you'll find a link in today's show. Notes Foreign. 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. Able now 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 in this episode of the podcast, we've covered discoveries that are paving the way toward what I consider some pretty big things. And I think we can safely say that being able to prevent Ms. Would be a very big thing. The global Ms. Research community has taken a significant step toward that goal, and in a moment, the National Ms. Society's Executive Vice President and Chief Research and Medical Affairs Officer, Dr. Bruce Bebo, is going to walk us through what Ms. Prevention is all about. We're always fortunate when the National Ms. Society is Executive Vice president of research. Dr. Bruce Bebo joins us for a conversation. Welcome back to the podcast, Bruce.
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Great to be with you, John. Happy New Year.
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Happy New Year. You know, a couple of weeks ago I came across a paper that had just been published. It recapped an international workshop that took place last spring, and this workshop was focused on developing a global research agenda aimed at preventing Ms. Now, the paper caught my attention because while I've seen and read lots of research focused on steps towards stopping disease progression or even identifying potential cures for ms, I think this may have been the first time I saw researchers committed to preventing multiple sclerosis. So before we get to that paper and that workshop, can you bring us up to speed on this concept of Ms. Prevention?
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B
Prevention is one of the pillars in the Pathways to Cures Research Roadmap. So you might recall that ROADMAP outlines three cures for Ms. Stop, Restore, and End, and the end cure we defined as prevention. And prevention can take two flavors of prevention that we're thinking of from a scientific point of view. One is referred to as primary prevention and one is referred to as secondary prevention. And I'll define what I mean by those. So primary prevention will be accomplished once we know what the critical risk factors are that trigger Ms. And what we know the critical genetic risk factors are for Ms. And how they interact with each other. For example, we can think of the genetic risk for Ms. Perhaps contributing about 30% of the risk to developing disease. And the reason why we say that is when you have an identical twin that has ms, the other twin has Ms. About 30% of the time. So to try to kind of put a number on it, that's not precise, but we think of the, the genetic component to the risk for Ms. Of being about 30%, which means the rest is related to the environment, pathogens or infectious agents, modifiable risk factors, and environmental exposures being Perhaps the other 70% contributing to the risk. So not much we can do about the genetics, our genetics, but we certainly can understand better the interactions between genetics and environment, understand what those key triggers are and when they're modifiable, learn from that and reduce exposures to these triggers for Ms. So of course, I'm quite sure we've talked about this on your podcast in the past, but ebv, of course, being one of the leading risk factors for Ms. And while there's not anything we can do about it right now, there's a potential to develop a vaccine and test that hypothesis that EBV is necessary and sufficient to cause Ms. So that's primary prevention. Are there risk factors we can identify? Can we prevent or modify exposure to those risk factors and prevent Ms. From happening in the general population? The second idea around prevention is called secondary prevention, and that's being able to identify people who are at high risk for developing Ms. And again deploying strategies that are modifiable to prevent Ms. From happening in people who are at high risk for Ms. So I'll share a little bit more what I'm trying to explain there. So we know what some of the risk factors for Ms. Are, things like childhood obesity and smoking. We know that if you're a first degree relative of someone with ms, your risk is higher. We know that if you live in a northern latitude, your risk may be higher. We're starting to, by using artificial intelligence, find patterns in healthcare utilization and people that went on later to develop Ms. That might tell us that you're at high risk for developing Ms. So the vision I have for secondary prevention, John, is we take all this information, we can calculate a genetic risk score, we can understand what your exposures are to environmental risk factors like ebv. We can start to get a sense of whether you're engaging with the healthcare system in a way, in a pattern that is indicating there's a risk for Ms. And identifying people that are at high risk and identifying people in the very, very, very earliest stages of disease, perhaps even before the central nervous system becomes involved. So we know there are changes to people's immune systems who have this genetic background and have exposure to these environmental risk factors. Again, I think AI might be able to help us here identify patterns in the immune system in the peripheral blood that could tell us somebody's immune system has been perturbed in a way that they're in this pre Ms. Stage. And we could stop that immune system from getting to the nervous system and prevent Ms. From happening in the first place. So I would call that secondary prevention. That's not prevention in the general population, but it's prevention in people who may be at high risk for developing the disease. So I think we're closer to secondary prevention than we are to primary prevention. And the tools that we need to identify people who are at high risk for Ms. Are starting to come together right now. So I'm really excited, particularly about the opportunity we have in secondary prevention and identifying people at very high risk for Ms. And intervening before they actually develop.
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A
Any clinical signs of Ms. That is an amazing vision. And the fact that we're on the cusp of perhaps achieving some of that is really exciting. So let's drill down a little bit. What can you tell me about that workshop that took place last April on this topic?
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B
Yeah, so that workshop was an effort by a growing group of Ms. Organizations that were all present at the meeting we had a few years ago in New York. John, I think you were there too. Our Pathway Secures research meeting that we had in New York. And like maybe three years ago, I think it was. And that's where we refined this Stop, restore and end pathways for pathways to cures. And it became clear, I think, in that meeting that the opportunities for prevention were super exciting. And so there is a group of global Ms. Organizations that have committed to work together to accelerate progress on pathways to cures, and a group within that group that has been inspired, like I have, about the possibilities of prevention that are pooling resources a little bit. John, like the International Progressive Ms. Alliance, it's not quite to that level of sophistication yet, but it's sort of the beginning of something like that, where the leadership from the global Ms. Societies, recognizing this opportunity, recognizing that we can go faster and make more progress if we work together. And this meeting was a first step in that direction. So bringing, I think it was about 50 thought leaders from around the world. It was hazard duty page on this was in Lisbon, if I'm remembering Portugal. So really great environment to have this meeting where we spent several days together charting out where the opportunities are in prevention. And I can share. While there aren't immediate plans to deploy resources, they are starting to come together. We are starting to work together to develop funding opportunities and identifying areas where we could make investments to accelerate progress, particularly in this topic, I would just say of the secondary prevention.
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A
This work is being led by our friends at Ms. Canada and Ms. Australia. Will the National Ms. Society here in the US Also have a role in this?
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B
All right, so let it be officially declared that, yes, we will have a role in this. John, I'm very, as you can tell, I think by the tone of my voice and the comments I've made that I think this is a very promising, exciting area. And we are grateful to the Ms. Society of Canada and Australia for, for leading this work. As you know, the Ms. Society in the United States is leading the International Progressive Ms. Alliance that is a large body of work and perhaps might be challenging for us to lead two big, large bodies of work like this. So we are grateful to our friends and colleagues in Canada and Australia for leading this. I have pledged to them. So this isn't a surprise that we are also committed to supporting this work, both financially and intellectually.
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A
So I think you've already started answering my next question. What are the next steps in developing this global research agenda?
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B
That may be a question to ask our friends in Canada and Australia. So I don't want to steal any thunder from our friends and colleagues there, but I know there is another meeting planned for this summer and I believe that the agenda will be focused on where we can make investments that are strategic and impactful. And then out of this meeting we would absolutely start announcing funding opportunities for the scientific community to apply to in those areas that we feel have the greatest opportunity to move the needle on this. And maybe just to add to that, John, while this global effort is coming together and focusing and aligning resources, we're all individually investing in these areas of research as well. So progress is being made in understanding what the opportunities are in prevention, both as part of this effort and then outside. Outside of the effort.
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A
That makes sense. Having seen and frankly been a part of watching and participating in the way the International Progressive Ms. Alliance has been able to truly influence the research agenda when it comes to progressive Ms. I think the alliance, frankly, is the ideal blueprint for how international collaboration, how working with global partners accelerates everything and brings those topics to the top of everyone's radar in the research community. So I think this is a wonderful way to progress.
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B
Yeah, I think we'll learn, we'll take the best sort of learnings from the alliance and we'll, you know, this is a slightly different topic and opportunities are, are, are slightly different. So we're going to learn for sure. It's the same players as you know, it's the same organizations, it's the same executive leadership and research leadership that have come together to accelerate progress and research and progressive Ms. That are lining up to do this work as well. So we will take the best parts of the alliance and we'll customize it and to the purpose of this work. And I'm excited about the opportunity and the progress we can make. You know, people often ask me, John, when I give talks, you know, when are we going to have a cure? It's of course a natural question and it's of course a hard one to answer and I'm not going to answer it for you now. But what I'll answer is of the three cures and pathways to cures, stop, restore and end, I think it's this end cure, the prevention cure that we're the closest to. So I think we can make real progress in the next few years. I have an idea of developing an Ms. Risk tool or early detection tool. And other neurologic and autoimmune conditions have these tools. So for example, Parkinson's disease has an early risk tool, type 1 diabetes. There's one approved treatment for delaying the onset of insulin dependent type 1 diabetes based on this sort of secondary prevention concept. So we can learn from our colleagues in these other conditions. And I am excited about the idea of developing a multimodal risk tool that takes into account your genetics, your environmental exposures, your engagement with the health care system, your EBV status, all of these variables and in the end churn out some kind of algorithm or formula that would be able to calculate, let's say like a little bit like a Framingham heart disease risk score. What's your 10 year Ms. Risk score? And then I can imagine my vision here is that that would hit some threshold at some point that it would trigger an MRI scan on a regular basis. You have no clinical symptoms, but you have enough circumstantial evidence, if you will, to justify from a financial point of view, starting to do Mr. Annual, or maybe more often MRI scans. So we catch Ms. Before it was ever even clinically apparent and start being able to treat it before it becomes apparent. I'll leave you with one more thought that this concept of radiologically isolated syndrome, so sometimes people get MRI scans of their nervous system for different reasons. They have neurological symptoms that their healthcare provider can't explain and they need to do imaging and they'll find imaging signs that look a lot like Ms. In people with no clinical symptoms of Ms. This is called radiologically isolated syndrome. And there have been two clinical trials now where these cases of radiologically isolated syndrome were collected and treated with Ms. Disease modifying therapies and shown a significant delay and the onset of Ms. With a disease modifying therapy. And I wonder, even in some cases, we may have already prevented Ms. In some people from those trials of radiologically isolated syndrome. So if we can find people with this RIS intentionally rather than accidentally and start treating them before any clinical signs appear, I think minimally we're going to delay the onset of Ms. By years, which would be amazing. And perhaps we might even prevent Ms. From occurring in some people. And that that's kind of the first step towards this secondary prevention.
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A
I always learn something new when I talk with you, but the other thing that happens is I come away from these conversations really energized. I caught your enthusiasm for the whole prevention strategy and, and its place and its values. So this is, this is really a wonderful direction that the world is heading in.
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B
Stay tuned. It's going to move fast, I think. Yeah. Going to move fast.
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A
Well, Dr. Bruce Bebo, I want to thank you for all you and the National Ms. Society do to support and fund Ms. Research around the world, especially now when research funding from our federal government is so uncertain. The Society's investment of over a billion dollars since its founding has perhaps never been more important. As always, thanks so much for talking with me today.
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B
Thanks, John. Have a good day.
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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 at realtalkms.com/439. 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. I'm John Strum. Thanks for listening. Stay safe and make healthy choices. Sam.