Melanie Cole, MS (Host): Welcome to Back to Health, your source for the latest in health, wellness, and medical care, keeping you informed so you can make informed healthcare choices for yourself and your whole family. Back to Health features conversations about trending health topics and medical breakthroughs from our team of world renowned physicians at Weill Cornell Medicine.

I'm Melanie Cole. And joining me today to talk about treatments for progressive multiple sclerosis is Dr. Jai S. Perumal. She's an Associate Professor of Clinical Neurology in the Department of Neurology and Neuroscience at Weill Cornell Medicine and an attending neurologist at New York-Presbyterian Hospital Weill Cornell Medical Center.

Dr. Perumal, thank you so much for joining us today. And I'd like you to start. Since I said the topic is progressive multiple sclerosis, can you explain the difference between relapsing-remitting MS and progressive for our audience?

Dr. Jai S. Perumal: Sure, Melanie. First, thank you for having me on this. It's a pleasure. So, we can just go into the topic right away. There are a couple of different forms of MS. The most common form of MS is relapsing-remitting where a patient has an acute onset of symptoms. And then, over the next several days or weeks, they recover. And then, depending on how the disease goes and their treatments, anywhere from a few months or a few years, they may have another attack. So, their clinical presentation is an attack, normal, an attack, normal. So, that form of MS is called relapsing-remitting. That's the more common form. About 85% or even 90% of patients are diagnosed with relapsing-remitting.

The less common form of MS is called primary progressive MS. In this case, patients don't start out by having the symptoms all of a sudden. It almost feels like the symptoms creep in. They may notice that they're not able to keep up with their spouses when they walk, or they may notice they are getting fatigued easily, their foot is dragging. It kind of creeps in, and it never goes away. The problems slowly build up. So, that form of MS is called primary progressive, where they don't have an up and down phase to their disease. It starts with these problems with gait, sometimes cognition that creeps in and slowly gets worse.

Now, when you look at the typical demographic, relapsing-remitting patients, the average age is in their 20s. There is a female preponderance in MS. The ratio is about 2.5 or closer to 3:1. So, that ratio holds for relapsing-remitting. While if you look at the primary progressive MS group, it's often diagnosed later, a couple of decades later. It's late 40s, sometimes early 50s. And the ratio of female to male is almost 1:1. So, there is a slightly higher male preponderance in that form of MS when compared to the female, but the ratio is still 1:1.

Now, you may also have heard about secondary progressive MS. This form of MS is essentially what happens to patients with relapsing-remitting disease. Over time, depending on how aggressive or uncontrolled their disease is, they may transition from having an up and down pattern to a disease course that is similar to the primary progressive MS, in that problems kind of creep in and now they are here to stay. So, since these patients had a relapsing phase in the beginning and then transitioned to this kind of slowly worsening problems, that form of MS is called secondary progressive. It's not a completely different form when compared to relapsing-remitting. It's just the latter stage of relapsing patients.

Melanie Cole, MS: Thank you so much for explaining that so clearly for us. Tell us a little bit about treatment options available for patients with progressive MS, how they differ from what you would do for someone with relapsing-remitting, and the goals of treatment, because I think that's the most important thing. If we know that this is something that does not go away or cannot be cured as we use that word, then what are some of the goals of treatment that you're looking to?

Dr. Jai S. Perumal: All our current treatments have shown excellent efficacy in relapsing-remitting patients with MS. And our goal in using some of these high efficacy treatments early in patients with relapsing-remitting is to delay or decrease the level of disability or possibly prevent our relapsing patients from entering into the secondary progressive stage where their problems go up. You know, the pattern of the disease will change. It'll go from up and down to a steady level. But that doesn't mean once they hit that steady level, their disease has to be on a downward trend or now everything is going to continuously get worse. So, our primary biggest goal with what we currently have, the treatments we have, is to use it early in relapsing-remitting patients so that they never have that much of a problem when they hit the latter part of MS. So, that's what we can currently do.

Now, we have a couple of medications, some of them have an indication for either secondary progressive or primary progressive MS. And in some patients, they may have an impact, especially patients who are relatively younger, who may have this kind of still an inflammatory phase, these treatments may have an impact. But unfortunately, the kind of efficacy we see with the existing treatments in relapsing-remitting patients with MS, we don't see in secondary progressive or primary progressive MS. At least for secondary progressive MS, you know, since they are patients who transition from relapsing-remitting, we can use these treatments early to delay or make the transition not so hard. But for primary progressive MS, it can be difficult when they don't respond to these treatments and that has been our biggest need in terms of our current treatments. There is a gaping need for us to get better in terms of treating progressive MS.

And the underlying pathology or what causes this kind of progression is different. In relapsing-remitting patients, most of the damage is caused by inflammation outside of the brain. You know, you have these immune cells that are circulating in the blood. They gain access to the brain and then they cause a lesion. And that lesion will cause a relapse. So, we are very good at controlling the immune system outside of the brain. We can control it either mildly or significantly depending on how aggressive we need to be to treat the disease so we can prevent relapses and hence control the disease.

But in progressive MS, the pathology is different. It doesn't appear that it is immune cells that go from outside to the inside of the brain causing problems, but it looks like there are inflammatory changes or injury happening within the compartment of the brain itself. These are immune cells that are residing within the brain causing this kind of slow injury versus these bouts of inflammation coming from outside. And they may be setting off other forms of injury like a neurodegeneration or oxidative stress. So, it appears that the inflammation or the kind of injury happening is different, and we have not been able to control what is happening within the brain the way we have been able to control this kind of immune system that's going from outside. Hence, the relative lesser efficacy of our current treatments in progressive MS. Many of our treatments don't get into the brain the way they can control the cells outside. And even if they get into the brain, we need to be able to better find the targets that cause injury in progressive MS to better address that.

Melanie Cole, MS: Wow. So, it's a lot to take in when we think about this. And you as a healthcare provider, Dr. Perumal, how do you determine then the most appropriate treatment approach for patients with progressive MS? Speak about some of the exciting approaches that you're using now and how with shared decision-making you're working with the patient to decide which ones that you're going to use.

Dr. Jai S. Perumal: Currently, even among the medications that we have, a few of them have indication for progressive MS. So, we start them on treatment and we hope that will work again for relapsing patients. Our goal is to prevent them from becoming secondary progressive MS. For primary progressive MS, we still use the existing treatments. And again, the goal of any treatment is to start early before more damage happens, because we are much better at preventing than reversing damage that has happened.

In what's coming, what we can see happening now in progressive MS is we have definitely gained a lot more knowledge into what may be causing this. So, I'm hoping that with the current advances in treatment, and there are a few clinical trials, some of them are in phase III and some are in phase II that are specifically targeted at progressive MS. And that is where the biggest research interest is in MS.

Now that we seem to have a good handle on relapsing patients, all the recent, you know, impetus for research funding, everything is being focused on progressive MS. So, I think this kind of effort and resources being put into this is going to result in something effective for progressive MS soon. So, we have a few treatment trials. One is repurposing existing drugs, you know, medications that may have been used for other diseases. They seem to have some kind of an anti-inflammatory effect. They are being studied in some of the medications we use for cholesterol or diabetes or seizures is now being tested in progressive MS.

Another approach is vaccines, reverse vaccines. If something has triggered the immune system to make cells that is now attacking the brain, can we vaccinate them to reverse that triggering? Inverse vaccination, that's being studied. Another modality is using one's own immune cells to go in and kill the bad immune cells that are now targeting the brain. That's called CAR T-cell therapy that's been used in cancer. It recently got FDA approval to be studied in MS and phase II trials, I think, just started. So, it's a lot of exciting news for people who have been desperately waiting for something specific to progressive MS. And I'm sure between all these approaches, we will have something that is effective.

Melanie Cole, MS: This is really an interesting and exciting time in your field, Dr. Perumal. What advice, as we wrap up, would you offer to patients with progressive MS and their caregivers while they're navigating treatment options to optimize their care and advocate for the best healthcare they can get?

Dr. Jai S. Perumal: One is sometimes when patients see a neurologist, they think neurology is already a specialized field, so they don't need to seek the next step. I advise everybody who has MS to find that neurologist who specializes in MS, because the field is changing. So many new treatments, so many new management strategies are coming into effect. So, go find a neurologist who specializes in MS so that they're kept up on the latest developments to establish care.

And then, even with the current treatments we have, we have to use them in the most effective way, start them as early as possible. In addition to going after the underlying disease process, there are so many other aspects to controlling one's disease in terms of symptom management, diet, exercise, all the complementary therapies, all of them plays a big role. So, we have to approach a patient with progressive MS in a comprehensive manner, not just look at controlling the immune system, but what else can we do to make sure we are controlling the disease the best we can and we are providing them opportunity for the best life that they can live.

Melanie Cole, MS: Thank you so much, doctor, for joining us and sharing your incredible expertise in this area today. And Weill Cornell Medicine continues to see our patients in person as well as through video visits. And you can be confident of the safety of your appointments at Weill Cornell Medicine.

That concludes today's episode of Back to Health. We'd like to invite our audience to download, subscribe, rate, and review Back to Health on Apple podcasts, Spotify, iHeart, and Pandora. And for more health tips, please visit weillcornell.org and search podcasts. And parents, don't forget to check out our Kids Health Cast. I'm Melanie Cole. Thanks so much for joining us today.

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