Podcast Host / Moderator (2:39)

Progressive Ms. Yeah, it's been a revolution.

Dr. Jamie Holloman (2:43)

In terms of the care that patients get. And a lot of really good clinical studies showing if you can treat people early with intensive disease modifying therapy, you can reduce progression overall.

Dr. Barry Singer (2:53)

Yeah. One of the changing concepts here is, you know, we talk about worsening. Some people can get worse after an attack, so we call that raw relapse associated worsening. And so some people just get worse right after an attack and live with that change in terms of disability. But then the harder part to treat is what we call pira progression independent of relapse activity. And this is when you're not having relapses, but things are slowly getting worse. And so this is the tricky part of progression that we're really trying to focus on.

Dr. Jamie Holloman (3:30)

Any thoughts on how common progression is in your average Ms. Patient?

Dr. Barry Singer (3:34)

Well, you know, the old trials before we really had treatment, if you follow people over 40 years, unfortunately, about 90% of people went on to progressive Ms. But now we're seeing in more recent trials with higher powered drugs, we're getting to maybe 60% of progressive. And. And with our latest generation of drugs, hopefully that's going to even get less than that.

Dr. Jamie Holloman (3:58)

Absolutely. That's certainly the goal.

Dr. Jamie Holloman (4:00)

Overall. When you're seeing a patient in clinic and you're worried about progression or if a patient asks you about progression, how do you typically describe progression to a patient in the clinic?

Dr. Barry Singer (4:10)

So when we talk to individuals with ms, frankly, they tell me so, you know, I sit back and like to listen to someone tell their story. And frequently they'll tell me, you know, I'm just not doing as well. I'm having a hard, harder time walking. I've gotten slower. Some of our patients will talk about they could walk two miles before their foot would drop. And, you know, now they can go a mile and a half and then, you know, six months later, just a mile. So sometimes you can hear that as you talk to patients about their mobility. Sometimes it's a caregiver, the spouse, the friend, the daughter that comes in and says, you know, the person living with Ms. Is having more cognitive problems, more memory problems, word finding difficulty, and they notice a decline in cognition over time. If you're living with Ms. And you've noticed changes, then it's important to convey those.

Dr. Jamie Holloman (5:06)

Absolutely. Any thoughts on what causes this underlying progression in multiple sclerosis?

Dr. Barry Singer (5:12)

Well, there seems to be a number of factors going on. One's actually injury to the nervous system. So we know the immune attack happens and the immune system turns on itself, attacks myelin, the coating of the nerves. But it's not just the coating of the nerves that get damaged. You know, sometimes part of the nerve called the axon gets attacked, so that can lead to permanent damage to the central nervous system. We also know there's failure of remyelination, so the ability to recoat the nerves gets worse as patients age. And so repair is not as good. And we call this category of neurodegeneration losing ground. But there's also some chronic inflammation going in the nervous system. And on a recent podcast, we're talking about spinal cord pathology. And there's actually active inflammation going on in people throughout their life. Chronic lesions in the brain and spinal cord have a group of cells called microglia. And these microglia create a rim around the edge of lesions, and they cause chronic inflammation, inflammation, and damage to the nervous system. Some of these lesions are actually slowly expanding lesions, so they keep getting bigger. And so we know these microglia play an important role, so targeting them may be useful. We also know the brain and spinal cords has an outside coding called the meninges. And along these meninges, inside the nervous system is clusters of B cells that create chronic inflammation. And so if we can target those B cells, we may be able to prevent some of that progression that we see in people living with Ms. And then I think another important topic is age related changes. So, unfortunately, as we all age, our brains are shrinking, and this happens, unfortunately, at a faster rate in people living with multiple sclerosis. And when you're young and healthy and you have some lesions, you have a lot of extra brain to compensate. But unfortunately, as we age, we're losing brain tissue and it makes it harder. So because of all these reasons, it's really important that we get an early diagnosis with someone with Ms. And get them on highly effective treatment so we can prevent this damage. So when people age, they have a lot less lesions on their brain and spinal cord allows them to adapt.

Dr. Jamie Holloman (7:35)

Well, yeah, you mentioned a little bit about some of the therapies. Would you mind going in a little bit of detail when you see a patient in your clinic with concerns of progression, what type of medications you might think about to try to help with the disease?

Dr. Barry Singer (7:48)

So that's definitely an unmet need. Jamie, we really don't have great treatments for progressive disease. We have some positive data in some clinical trials, so we have a couple agents that have been shown to be positive in progressive patients, but unfortunately, a lot of trials have not been positive. In the mid-1990s, there was a clinical trial looking at the first Ms. Drug in secondary progressive Ms. And that's beta seron for some of you out there in different parts of the world. Beta Fearon. So this was studied actually in two trials. One was in a European study and one was a North American study. And interestingly, it did slow down progression in the clinical trial in Europe, but did not work in North America. So if you go back and look at what patients were enrolled, it turned out that North American patients were older, they had Ms. Longer and had less relapses. So it looks like younger patients seem to respond better in preventing progression. Another important trial that we were involved on here at our center was Mason. So this was the expand trial and this was a nicely done trial looking at secondary progressive Ms. And the patients range from 18 to 60 years old. They had a moderate amount of disability. At the most people would needed a walker or double crutches to walk. We call that an EDSS of 6.5. And the bottom line is it did slow down Mason, did slow down progression, so by about 21%. So it did show a benefit in slowing down progression, but not the most robust number. The side effects of Mason included elevated liver blood tests, increase in blood pressure, swelling, back of the eye called macular edema and increased rates of shingles. So overall the data for Mason was favorable in secondary progressive Ms. Have there.

Dr. Jamie Holloman (9:44)

Been any other current Ms. Disease modifying therapies that have shown a benefit on progression?

Dr. Barry Singer (9:49)

We do have one trial in primary progressive ms, large trial with ocrevus or ocrelizumab. And so this was studied in primary progressive Ms. Patients, not the secondary progressive that we were talking about, but the percentage of patients that had confirmed disability progression was reduced by 24% compared to patients on placebo. So this was a big win for primary progressive patients because the only FDA approved treatment for primary progressive Ms. But again, we don't really have a big phase 3 clinical trial studying secondary progressive Ms. With the B cell treatments. They are approved for activ secondary progressive Ms. So these are people that are progressive but still have new relapses or new MRI activity. So if you are still having inflammatory activity, which we consider relapses into MRI activity despite being progressive, you would be a candidate for these medications.

Dr. Jamie Holloman (10:48)

Absolutely. And I think with all your discussion thus far, you've highlighted a good fact which is the data is pretty complex both in terms of the types of patients that are in these various different studies and the effect sizes that we're seeing. So it's a very nuanced discussion, but nevertheless has these intermittent Glimmers of hope. Which kind of brings us, I think, to a new medication on the horizon that a lot of us are pretty excited about. Tolobrutinib, which is a BTK inhibitor or a Bruton's tyrosine kinase inhibitor. I think a good place to start would be maybe if you could tell me a little bit about Bruton's tyrosine kinase and what this enzyme does and why it was targeted for this medication.

Dr. Barry Singer (11:29)

Yeah. So this is Tolobritinib is an oral medication? Well, it's experimental medications. It's not FDA approved yet, but it's used for targeting cells in the nervous system. By blocking btk, it allows impairment of a couple different types of cells. One is microglia and one are B cells. So I mentioned microglia are these little cells that are on the rim of chronic lymph lesions and cause continued inflammation in the brain of people living with Ms. And so the idea is, could you target these cells in the nervous system and prevent progression? The other thing is that it affects B cells. So many of our drugs with Ms. Are going after B cells, we find that really reduces new inflammatory activity. One of the advantages of a molecule like this is that it can get into the brain and the central nervous system. Many of our antibody therapies don't get into the brain in very high concentration. The coverings of the brain and meninges kind of blocks them out. And we have something called the blood brain barrier that blocks out antibodies. But this molecule, tolobrutinib, can get into the nervous system, and we think it's going to go after those microglia and the B cells.

Podcast Host / Moderator (12:44)

Could you tell me a little bit.

Dr. Jamie Holloman (12:45)

More about some of the clinical data that we're getting on tolebrutinib?

Dr. Barry Singer (12:48)

Yeah. So we participate in the clinical trials here, and it's exciting to see this go forward. One of the clinical trials was Hercules. So Hercules was in the secondary progressive Ms. Patients. And so people were randomized 2 to 1. So twice as many people got tolebrutin as placebo. Patients that entered the clinical trial had a moderate amount of disability. Some of them needed a walker to ambulate, and the patients were randomized to receive toleprintin or placebo. When we look at the age of the patients, on average, the age was about 49, so a little older than our relapsing clinical trials, where, you know, on average they're about 35, 36. And in general, they had Ms. Relapsing, remitting Ms. Was initially diagnosed about 17 years on average. So these people were definitely not active patients. They were more in the progressive phase. And their last relapse, on average, was seven and a half years ago. So this is very similar to many of my patients in clinic, you know, who are older patients and are having more progression and less relapses. And so the bottom line is the patients on tolebrutinib were less likely to have progression of disability. So this was a 31% benefit. Interestingly, also, there was a small group of patients that actually did better. So during the clinical trial, they actually had improvement. So we call that confirmed disability improvement. And it was 8.6% in the tolebrutinib group and only 4.5% in placebo. The tolobrutinib didn't have the most robust MRI data. It was about a 38% reduction on new and enlarging T2 lesions. So these are some of the brain lesions that we look at for Ms. In terms of risk. You know, unfortunately, there's always a trade off here. Right. So respiratory infections were more common in the tolembutinib group than in placebo, and this included COVID 19 was a little higher nasopharyngitis and influenza or flu. The other concern was liver enzyme abnormalities. So you can look at the normal range of liver enzymes, and about a half a percent of patients had 20 times above the upper limit of normal. So that's definitely a potential concern here and will require significant monitoring if FDA approved.

Dr. Jamie Holloman (15:13)

Yeah. The hope would certainly be, given the signal that it might be changing the liver enzymes, is if we carefully monitor patients on this medication, we can catch those patients who may be having some elevation in liver enzymes, take them off the medication. You mentioned the Hercules study. There was also the Gemini study with tolebrutinib. Would you mind sort of just briefly touching on that and telling us what that showed in terms of ms?

Dr. Barry Singer (15:38)

Yeah, so we had studied tolobrutinib and Hercules, which is in the secondary progressive patients. There was actually a primary progressive trial too, but we're waiting on that data. And then Gemini 1 and 2 were the relapsing clinical trials. So, again, these were younger patients. So on average they were about 37 years old and they had relapsing forms of Ms. And was primarily relapsing, remitting Ms. And so, you know, it was compared to not placebo, but tariflutamide. So it's another once a day pill. The bottom line on relapses was about the same. So the relapse rates were really no different than tariflid M. It did not outperform it. You know, the relapses were pretty low. It was equivalent, about one relapse every seven to nine years on both drugs. So they both did perform fairly well, but not a significant benefit on relapses. But interestingly, Jamie, when they looked at the data looking at progression of disability, looking at worsening disability over time, that was a 29% benefit for being on tolebrutinib than teraflutamide. So even though they were same on relapses on disability, tolebrutinum was 29% better. So it kind of reflects what we saw in Hercules where an impact on disability. Again, you know, is it because it's going after the B cells and the microglia within the nervous system? We don't know. But overall positive results.

Dr. Jamie Holloman (17:04)

And this is something that, you know, is still in the works. As you mentioned, this is a medication currently undergoing FDA approval. But if I had to put you on the spot and maybe say with the perfect patient that you envisioned, a maybe trial telebrutinib in the future, what would you say?

Dr. Barry Singer (17:19)

Well, I think it's pretty open. There's going to be a lot of patients that do have progression. Unfortunately, we hear it every day. So I think it's part of the discussion with patients and then I think we're going to have to monitor them to see if they have new MRI activity if you do switch over. Someone highly active with numerous enhancing lesions. I'm probably not going to pick this agent, but many patients kind of fall in between. And so we have to kind of figure out who's good candidate. And like anything else, it's the conversation we have with the patient and having a discussion about what we find appropriate. You know, one day it would be nice to have a little bit of combination treatment. You know, so one drug that's very effective for progression and one that's very good at shutting down new contrast enhancing lesions. So ideally combination. And there has been some data in oncology using BTK inhibitors with B cell depletion. So hopefully one day we may be headed that way, but not yet.

Dr. Jamie Holloman (18:13)

And I think a burning question our listeners with multiple sclerosis might have is when could they expect tolebrutinib to be available?

Dr. Barry Singer (18:22)

So fortunately, tolabrutinib is under expedited review by the fda and we should hear something by the end of September of 2025.

Dr. Jamie Holloman (18:30)

Dr. Singer, I just want to thank.

Podcast Host / Moderator (18:32)

You for all your work that you do.

Dr. Jamie Holloman (18:34)

I'm glad we were able to kind of turn the mics around and get your knowledge on this point. Point. You're a clinical researcher and have actively contributed to all these studies, so it's great to have that firsthand perspective for our audience.

Dr. Barry Singer (18:46)

Well, thanks, Dr. Hallman. It's great to have you join the Ms. Living well podcast and I'm really looking forward to your conversation with Dr. Lagank.

Dr. Jamie Holloman (18:54)

Absolutely.

Dr. Jamie Holloman (18:55)

Pleasure talking with you.

Podcast Host / Moderator (19:08)

Our next guest is Dr. Christopher Legank. Dr. Legank is the founder of North Central Neurology Associates in Coleman, Alabama, a leading center for patient enrollment in clinical trials on new oral multiple cirrhosis medications. He received his medical degree from Meharry Medical College School of Medicine in Nashville, Tennessee and later completed an internship in internal medical medicine, neurology residency and a two year neuroimmunology fellowship in Ms. At the University of Alabama in Birmingham. He also created the Joan P. LeGank Ms. Center in honor of his mother. Dr. LeGank, thanks so much for joining our podcast.

Dr. Christopher Legank (19:43)

You're welcome. Thank you for having me.

Podcast Host / Moderator (19:45)

I think a great place to start would be what initially got you interested in working with Ms. Well, it was.

Dr. Christopher Legank (19:50)

Kind of put upon me. My mom had ms, so that kind of set the wheels in motion that I wanted to have an impact on this disease. Also from a caregiver perspective, able to hopefully relate to those caring for people with Ms. And understand that dynamic as well.

Dr. Jamie Holloman (20:08)

Yeah, absolutely. That's incredible. And it's something we share in common. My mom was also impacted by multiple cirrhosis and totally agree. It kind of sets the stage for how you think about medicine and just makes it incredibly fulfilling to work with patients with multiple cirrhosis. And I know that your Ms. Center is named after your mother, Joan Legank.

Dr. Christopher Legank (20:29)

Yes. Joanne P. Le Gank Ms. Center. That's right.

Dr. Jamie Holloman (20:31)

Yeah. So that's incredible.

Podcast Host / Moderator (20:33)

Great.

Dr. Jamie Holloman (20:33)

Well, our topic today is progressive symptoms in patients with multiple cirrhosis. And so this is something that comes up pretty commonly in clinic. And so I just wanted to get your perspective. And as an Ms. Clinician, how do you think about progressive symptoms and multiple cirrhosis?

Dr. Christopher Legank (20:48)

It's a huge subject. The more we learn, the more we know. We don't know. With this condition, progressive symptoms can occur because there's actual progression of the disease and the progressive symptoms can also be due to stress and stress associated worsening, I think is underappreciated and has a huge impact on progression of symptoms, which fortunately Then can be reversed if we deal with the cumulative stressors. But progressive symptoms of cognitive decline, fatigue, walking impairment are quite common in ms, as you know.

Dr. Jamie Holloman (21:26)

Yeah, absolutely. In patients dealing with these symptoms, how do you typically address it in clinic or how do you start the discussion?

Dr. Christopher Legank (21:34)

So first is to identify really is this progression due to the disease progressing, Is it due to stress aggravating the reserve that a person has to compensate for the prior areas of damage, or is it due to some, some other condition that's going on that can certainly aggravate fatigue or whatnot? So it's really trying to get at the core of what's going on. Do we need to change our disease modifying therapy because it's not holding a person, or do we need to identify the stressors and address those? And then of course, just at the end of the day, it's trying to treat the symptoms themselves.

Dr. Jamie Holloman (22:09)

Absolutely. One of the common complaints that patients have will be progressive type symptoms and specifically they'll mention that they just kind of feel a little bit worse even though they're on medication. Maybe the medication seems to be helping, but still they're getting a little bit.

Dr. Jamie Holloman (22:23)

Weaker, they don't feel as sharp as they used to.

Dr. Jamie Holloman (22:26)

They maybe are stumbling a little bit more.

Podcast Host / Moderator (22:28)

When you're seeing a patient like that.

Dr. Jamie Holloman (22:31)

Specifically, do you then look on the exam for changes? Do you order new testing, do you sort of talk with them to really parse out how do you start making the determination of maybe stress related factors versus progression of the disease?

Dr. Christopher Legank (22:44)

So that's going to start with a history and just delving into what's going on with patients. If really can't identify any stressors, then we're going to do a little bit of testing. So patients with Ms. Are not immune to other problems. And although we may have tested for thyroid disease and B12 deficiency and things like that, vitamin D deficiency in the past, we may have to revisit that because those conditions certainly can have an onset later in life as well. Depression and anxiety are common comorbid conditions in MS, up to 40% in each. And addressing those and the impact they have on their overall functioning needs to be done. So it's really kind of getting a history. If you can't identify anything, do a little bit of testing. And then of course MRI testing and testing for Ms. Worsening is something we do if we don't have answers there.

Dr. Jamie Holloman (23:35)

So let's say you're working with a patient and we're sort of able to rule out some stressful factors. We're Able to check a B12 level. Tsh. Those look okay. MRI is repeated. That looks all right. But still they're having some progressive symptoms, maybe some cognitive decline or some difficulty with walking. What do you typically do with patients in that case?

Dr. Christopher Legank (23:56)

So there, I guess I'm still a little unsure if they have progression of Ms. Or there are other things involved. And I probably, if I don't see any objective evidence that Ms. Is advancing, I'm not so quick to change their disease modifying therapy and probably would symptomatically treat that person. So fatigue and cognition are intimately associated. There's primary fatigue of ms, which is very common, but sleep disorders and just a host of things affecting a person's energy level. So working on that, there are certainly medications that are wakeful agents and stimulants that can help and then paying attention to lifestyle. We know that when a person's out of shape, it takes a lot more energy to do things. So we try to encourage them to get into shape and acknowledge that that's a very slow process.

Dr. Jamie Holloman (24:46)

A question I get from patients. It's kind of a tug of war where they'll try to get up and get moving around, but then the fatigue kind of gets the best of them and so that'll knock them out for a couple hours. So they always ask, you know, how much can I do? You know, how should I think about getting up? Increasing activity. Do you have particular guidance from that standpoint?

Dr. Christopher Legank (25:06)

Yeah, it's very individual. It's wherever they are, just trying to slowly advance that. So if it's walking, it's walking a little bit more. Make sure that I know heat is not an issue. Us here in the south have to contend with that most of the year. So cooling vests and cooling devices can be helpful. Pool therapy is something that can help a person to get into a little bit better shape as well. That's one approach. But it all depends where a person's starting as to what we're going to recommend as far as advancing goes.

Dr. Jamie Holloman (25:37)

You mentioned sometimes you'll consider drugs to promote wakefulness. Are there specific drugs that you think about in patients with fatigue?

Dr. Christopher Legank (25:44)

So Armodafinil and Modafinil or Nuvigil Provigil are two agents that we generally will start with. They kind of complement stimulants. So sometimes we use combination of wakeful agent and N as stimulants. The stimulants or the Adderalls and Ritalins and Vyvanses, et cetera, et cetera. Those types of medications. Fatigue being so common 90% of people with Ms. Affected by fatigue at some point and significant impact in over 60% of people. People are hesitant to take medications, especially stimulants and oh, that's a bad drug. And it's controlled. And we certainly would. I love for a person to find ways to have energy other than medications, but just frankly, most of the time they're going to require a little assistance to optimize function. It's just trying to improve quality of life. That's the bottom line with these symptomatic treatments. Is your quality of life better for having taken this? And that's taking into account side effects, cost on the adverse side versus benefit that you derive. And it's kind of working with that to really, you know, just allow a person to function as best as they can neurologically.

Dr. Jamie Holloman (26:54)

Yeah, that's absolutely right. I do get that same comment where, yeah, I'm worried about the addictiveness potential.

Dr. Christopher Legank (27:00)

You know, and oddly enough, I really don't see our patients getting quote, unquote addicted to these medications. You know, we may have to adjust dosing to get to the right dose, but once we're there, generally people are pretty content and stable at that dose.

Dr. Jamie Holloman (27:17)

I totally agree. You made a great point that, you know, roughly 90% of patients deal with fatigue. I'll find sometimes in patients and with patient family members, there might be a little bit of an education gap where family members might think, oh, this isn't necessarily the multiple cirrhosis or there's something else kind of personally that the patient is just not motivated or doesn't want to get up and do things, which is really heartbreaking when you hear it. And I think it's always helpful to get that message out that this is incredibly common, incredibly disabling, and so patients don't feel alone and that they're somehow not managing their disease well if they're experiencing a trendous amount of fatigue. Are there other things you look at when someone comes in with a kind of chief complaint of I'm just not walking as well or I'm not able to get up and kind of move around as easily as I used to?

Dr. Christopher Legank (28:05)

Sure. In our clinic we do a 25 foot time walk for everybody before I see them, so the nurse will walk them so that I have a little bit of an objective measure that may go along with their complaint of walking? Gee, they're not walking quite as well. There are other things, of course, arthritis, DJD of the spine, other things that can impact their walking and for that matter, hand grip, you know, Difficulty gripping things can be due to arthritis. They just don't have the flexibility of the joint, so they get weaker. But with walking in particular, it's kind of assessing. Is there something else going on? People can have neuropathy, et cetera. There's also endurance issues. So you may see someone walk and they seem to be walking fine, but a quarter of a mile down, which we don't assess in the clinic, they have a foot drop or their hip flexor is weakening and they're just unable to lift their leg that we don't see in clinic. So we kind of try to get a history. Balance certainly can be off when they change their vision. So if they have, we call proprioceptive difficulties or difficulty with knowing where they are in space because of a spinal cord lesion, for example, they don't have a visual focus, and they're relying on those sensors from their joints, and it's not coming up through the spinal cord, then they fall a lot. So walking can be due to something like that. We see that pretty commonly. So we try to be attentive to the different things that can impact walking. Now, there is a medication that I think is terribly underutilized, and that's Dalfamperidine or Empira. So it's a medication that can actually improve strength, improve walking by improving signaling through scar tissue and by blocking potassium channel. So it's just. It's an endurance pathway medication. It's misperceived as being just a walking aid. And it does help that, but it helps endurance in general. And so if patient hasn't tried that, has issues with endurance and some aspect of their neurological system, then I think that's a medication that can be helpful.

Dr. Jamie Holloman (30:04)

In those situations where maybe you kind of do the full optimization and make sure that everything is well treated from a symptomatic standpoint. Are there patients that you would consider switching disease modifying therapies or think about changing Ms. Treatment options?

Dr. Christopher Legank (30:20)

The area the central nervous system sometimes not imaged is the spinal cord. And the spinal cord certainly contributes a good bit to gait difficulties. So person comes in with their maintenance MRI of their brain and there's no change. Great news, but I'm not walking quite as well. And we're thinking it's something else. We need to remember that spinal cord disease occurs too, and we need to image that area sometimes to look for problems there. And there are 15 to 25% of people have asymptomatic or silent spinal cord lesions that might impact an eloquent area A little bit. But if we at the end of the day don't see any lesion that's causing difficulty, there still may be some things that are happening from an Ms. Standpoint that's making their walking worse. And I think that if we're watching someone kind of decline before our eyes and addressed all those other issues, I think discussing change in a DMT is certainly reasonable.

Dr. Jamie Holloman (31:21)

How do you typically frame the switch of medications with patients? Kind of knowing that there's some evidence that we have for benefit of progression, but not nearly as robust as the effect that it can have on relapses and inflammation?

Dr. Christopher Legank (31:34)

Yeah, that's a great question. I think managing expectations is important. Setting the appropriate outcome picture. So first, we don't have medications that reverse the disease or get someone better per se. So we have to say that if you do improve on this medication, that's wonderful, great. But our goal going in is to stabilize things and to keep you from getting any worse. So that's our objective here. So if your walking doesn't improve but you're not getting worse, well, that's a win. And just kind of as a maybe a soapbox sidebar here for one second. That I think pertinent is generic medications. Generic DMTs really against generic disease modifying therapies. They haven't been tested at that dose. You and I spend a lot of time in clinical trials proving this dose is effective or that dose is effective. Patients dedicate a lot of time and effort and sacrifice a lot to participate in these clinical trials to prove that we have a particular dose that does a particular thing. Generic medications may be 80% as effective or 120% as toxic as the standard medication. That's the bar that they set for a generic medication. So we're experimenting on patients to save money for the insurance company. I just think that's morally wrong for us to allow a condition that if you have one event based on a couple studies, one by Hirsch, one by Lublin, that about 40% of people will be permanently changed from a relapse. How can we offer medication that hasn't been tested?

Dr. Jamie Holloman (33:18)

Totally agree and thanks so much for mentioning that. So I'd be interested as we wrap up here if there are any interesting therapies in the future that are currently being studied or areas of research that you find particularly compelling. For patients with progressive symptoms who maybe aren't getting good treatment from our current.

Dr. Christopher Legank (33:35)

Therapies, the BTK inhibitors I think continue some of those continue in study to see how they do with progressive disease and hopefully we'll piggyback on the success of tolebrutinib. I'm sure there are an abundance of ones, some of which I'm not aware, but fraxalumab is a monoclonal antibody that works on what's called the CD40 ligand that's on B cells primarily and that medication may eradicate Epstein Barr virus senescent cells. We believe that possibly Epstein Barr virus is responsible for some of this progression of Ms. That's not proven as that's why we're in study, but that's kind of exciting to me. If that pans out to be the case, I think that type of treatment or therapeutic approach can be really helpful. I think the concept of biological aging and chronological aging is fascinating and that not every six year old's the same, that a person's biological age is maybe different than their chronological age. And Dr. Graves out of UC San Francisco has done a lot of work in looking at biological aging and she states the fountain of youth of treatment there is exercise. So kind of non medicinal things and approaches at how can we decrease biological aging, maybe the most important therapeutic intervention in progressive Ms.

Dr. Jamie Holloman (35:06)

Agreed.

Dr. Jamie Holloman (35:06)

And we've kind of seen a revolution in the treatments we can provide over the last 30 years and I'm hopeful that'll continue and that some of the treatments that you mentioned will sort of have that efficacy and really change things. Thanks so much Dr. Legang for chatting with me and taking me time and and thanks so much for everything you do for patients with Ms. You're welcome.

Podcast Host / Moderator (35:36)

Thanks to our listeners for downloading this episode of Ms. Living well podcast. Secondary Progressive Ms. Next Chapter Secondary progressive Ms. Is a stage of the Ms. Disease course characterized by the the gradual progression of Ms. Symptoms over months to years. When working up the possible causes of Ms. Disease progression, it's important to evaluate for a variety of different contributing factors including fatigue, pain, muscle loss from inactivity, mood disorders like depression and anxiety, and drug side effects. Treating these underlying issues with a combination of therapy and medication can significantly improve functionality of our current Ms. Medications. Symponomod has demonstrated a modest benefit in decreasing disability accumulation in secondary progressive Ms. And Ocrevus has shown a benefit in primary progressive Ms. A new class of Ms. Medications called the BTK Inhibitors is currently being studied for treatment of secondary progressive and primary progressive Ms. One such medication, Tolebrutinib, has shown a beneficial effect in decreasing disabilities disability accumulation in patients with secondary progressive Ms. But has a possible side effect of liver toxicity. It is currently under expedited FDA review and could become clinically available sometime in the near future. Thanks again to TG Therapeutics for sponsoring this episode. Keep in mind the topics we discuss in this show are strictly informational and not medical advice. Any change in your treatment should be discussed with your healthcare provider providers first. Our show is hosted by me, Dr. Jamie Holloman and Dr. Barry Singer and produced by Kerriad Harmon. Our theme music is the Gold Lining by Broke for Free. If you like the show, please share it with others living with Ms. I'd appreciate a positive view on Apple Podcasts. It helps more people find out about the show. You can follow me on X at BrainBoyNeuro and Dr. Singer at Dr. Barry Singer. More information about our guests and their websites can be found in the show notes for this episode in the blog section on mslivingwell.org thanks so much for listening.

Dr. Barry Singer (37:40)

This has been an Ms. Livingwell podcast.