S6E18 The latest research in exercise for MS with Dr Robert Motl

Robert Motl  00:00

People who have low levels of lifestyle physical activity, have more relapses have more lesions, they have greater deterioration of white and gray matter. You know they have a faster rate of disability progression over time.

 

Overcoming MS  00:16

Welcome to Living well with MS. This show comes to you from Overcoming MS, the world’s leading multiple sclerosis healthy lifestyle charity, which helps people live a full and healthy life through the Overcoming MS program. We interview a range of experts and people with multiple sclerosis. Please remember all opinions expressed are their own, Help others discover living well with MS. If you enjoy the show, please rate and review us wherever you listen to podcasts. And now let’s meet our guest.

 

Véronique Gauthier-Simmons  00:52

So hi, everyone, and welcome to this episode of The Living well with MS podcast. My name is Veronique Gauthier-Simmons, and I’m one of the facilitators of Overcoming MS with a special interest in exercise and physical activity. So I’m really, really delighted to welcome our guest today, Professor Motl. So thank you so much for accepting our invitation.

 

Robert Motl  01:20

Yeah, it’s really an honor to be here.

 

Véronique Gauthier-Simmons  01:22

Thank you. So you are a professor of kinesiology and nutrition. And also professor of rehabilitation sciences at the UIC which is University of Illinois, Chicago. Yeah, you are internationally known as a top researcher in the field of exercise and physical activity for people living with MS. So as a person living with MS, I want to personally thank you for all your work, because that is so important. It really makes a huge difference. So thank you. And you’ve been very, very busy, because you have authored. So over 650 And maybe maybe closer to 900 research articles, is that correct?

 

Robert Motl  02:09

That’s correct. We we’ve been very busy. And I, I emphasize the collective we it’s a team, it’s me, it’s colleagues, it’s postdocs, graduate students, undergraduates, it’s collectively a large number of individuals who contribute their their life and soul to this work. And, I appreciate your, your appreciation for the work we do. Because you know, the people with MS who we do research on really provide unique meaning and value to us as researchers because it gives us something really important to shoot for and really meaningful to shoot for, because a lot of times I think people do research, but they don’t really have a why. And people with MS give us a big why and what we do, and that powers us every single day.

 

Véronique Gauthier-Simmons  03:02

Okay. And actually, that was one of my first question, why this interest in MS. And what I mean is, did you find something in your earlier research? Do you find something where you thought, Oh, my God, I need to research that this sounds really interesting. And what is it that you found?

 

Robert Motl  03:21

Yeah, so that’s a great question. I get asked that question all the time. I think a lot of me finding MS and exercise was MS and exercise finding me if you will. So I completed a large number of trials for my dissertation work that were looking at single bouts of exercise and how they affected spinal reflexes, and people who have anxiety disorders. Okay, that sounds like a long way off from multiple sclerosis. So I did these studies and all eight of them for my doctoral dissertation failed to demonstrate what I was interested in showing. But what happened is, I always kept in the back of my mind, you know, our results and I also had this really voracious appetite to read. And so I go to the library every day and pick up journals and just random journals and read things. And so one day I was reading this article about spasticity and people with multiple sclerosis. And they were using a drug called baclofen, which is a GABA agonist to reduce spasticity. And they were measuring spasticity with the exact same techniques I was using in my dissertation research. So I thought, wow, I’ll write a grant to the National MS. Society, the United States to look at bouts of exercise to manage neurophysiological processes involved in spasticity and people with multiple sclerosis. They funded it. Oh my gosh, it was like the greatest day in my life right? For something that you don’t think anybody will find. And really, it took off from there. And I will tell you that it really, and I mean this like very sincerely, it really provided a lot of meaning to the research that I do. And in working with people with MS very closely in our research and helping to design some of our studies, has really been one of the most valuable, rewarding experiences that you can have in your career. And I could tell you stories that we could go on for like the rest of the day, but we’ll just leave it at it’s been really rewarding. And that’s where it started.

 

Véronique Gauthier-Simmons  05:44

Thank you. And what is the main? Or what are the key findings from your research? For someone who doesn’t know anything about, you know, exercise? And MS, what would you say? What are the key findings?

 

Robert Motl  05:57

That’s a good question. I’m going to keep it broad, and then I’ll dive into kind of what I think is a little bit more detail. I think the most important thing is is that people with MS need to know that exercise has profound benefits for a lot of the functional consequences symptomatic consequences and quality of life consequences. I think people with MS need to understand that exercise is very safe, the adverse event profile and serious adverse event profile is is very positive, it’s no different from the general population. And then I think people with MS need to understand that there are guidelines, and very specific guidelines about the dose of exercise that that people with MS should engage in, to safely accrue the benefits. So when I talk about the benefits, you know, we we know that that exercise has effects and beneficial effects on some of the most prevalent symptoms in MS. So, you think about fatigue as an example, you know, just about everybody with MS will tell you I have fatigue in various degrees, some very severe. And there is it a wealth of evidence that exercise is very effective at reducing fatigue and people with multiple sclerosis. Same thing occurs with depression, we know depression exists. And you know, 30 to 40% of people with multiple sclerosis and exercise is very powerful there. When we move into other things like walking, as an example, you know, that’s the most obvious symptom of MS that is people with MS start to have a little bit of difficulty in their ambulatory capacity, and that transitions to canes and rollators. And sometimes wheelchairs. And we know that exercise can can reverse that loss of ambulation. And then, you know, some of the really important things I would say, are quality of life and independence. So, you know, sometimes I think researchers underestimate the importance of quality of life and independence. But as humans, you know, our underlying spirit is to live a good life, and to be able to do the things that we want to do on a daily basis. Right. And, and we’ve demonstrated that exercise improves quality of life. And it optimizes the ability to live independent, high quality life where you’re able to do things like maintain employment, you know, do simple things like in America, you know, we talk about basketball a lot, go out in the driveway and shoot baskets with your kids, right? Go take a bike ride around the neighborhood with them, all of those things that are the little things that just mean so much.

 

Véronique Gauthier-Simmons  08:44

I’d like to come back to a key definition, I think for me is you talk about exercise. Yeah. So exercise means it is structured and with a purpose. And over the last couple of years, there’s been more and more people saying that we don’t need to exercise we just need to move and walk the dogs they are not talking about people with MS. With for the general population. But this argument as slowly moved into the MS community and I work with a lot of people with MS. I teach yoga and physical activity and a few times people told me but actually it’s enough we will if we walk I said no, but what do you think?

 

Robert Motl  09:32

I think you’re gonna put me in between a rock and a hard place? So you know, to be quite honest, we’ve pursued both research on on structured formalized exercise where for example, you go to the gym and we’ll ride a bike or a treadmill for a specific period of time at a specific intensity or go lift weights and and we know that that is beneficial. And we have prescriptive guidelines. And we can talk about those later. On the other side is, this thing that we call lifestyle, physical activity that is being active in everyday life. And we actually wrote this paper, it was kind of a goofy paper, but it was lifestyle, physical activity and MS. The new kid on the block, right, like, you know, bringing lifestyle physical activity into MS. What do we need to know, what do we need to do? And so we established this agenda to understand what do we know about levels of lifestyle, physical activity, it is very low, people with MS don’t engage in physical activity as part of their life. And I think that there are a number of reasons for that. We then looked at kind of the variables that explain that from a theoretical behavior change perspective. We also studied how low levels of lifestyle physical activity are related to outcomes. And MS. So people who have low levels of lifestyle, physical activity, have more relapses have more lesions, they have greater deterioration of white and gray matter, you know, they have a faster rate of disability progression over time, higher fatigue, depression, you know, all of those things. And so then we started to say, Okay, well, how do we change lifestyle, physical activity. So we have spent about, you know, 15 years developing these interventions, that are called behavioral interventions. And what we do is we teach people skills like self monitoring, goal setting, tracking, right, all of these different behavioral skills. And then we also help them identify opportunities to be physically active in everyday life. So for example, you know, people who are still working, you know, oftentimes, we work in close enough proximity that we can just get up from our desk and walk over to a coworker’s desk, it might take two minutes, and have a quick conversation instead of sending an email. And then we walk back, and that’s two minutes, that’s lifestyle, physical activity, that’s just walking. And if you can do that, you know, 10 times a day, what people don’t realize is that adds up to 40 minutes of physical activity. And this walk in this physical activity can have great benefits. And so we’ve developed these interventions to teach people these skills, they’re very successful at changing physical activity, during three to six month periods of the formalized intervention, then we take the intervention away, and all the coaching away and everything, and then we follow them six months later. And people still maintain that physical activity level that they learned, because we’ve taught them skills, strategies, techniques to be more physically active. And they’ve learned how to put physical activity in their life. And so they can maintain it, it’s easier. And as a consequence of that we’ve we’ve demonstrated that this approach, reduces fatigue, reduces depression, it improves processing speed, and improves walking performance, and quality of life. But to me, the real bang for the buck was, we did some research where we did a DEXA scan to get someone’s body composition. And it’s a very objective measurement of body fat, lean muscle mass and bone. And we were able to demonstrate that this intervention, reduce body fat, increase lean mass, and increased bone mass. So and that’s not something that that you can influence the machine to do better at, it’s just, it’s like an MRI, it’s biological data. And it really convinced us that this approach works. So we’ve really spun this approach off. And I would say, you know, the good thing is people with MS have two approaches to choices, right, they can engage in exercise, or they can do this thing that we call sitting less and moving more, that is trying to reduce the amount of time that you spent sitting or laying and not moving and increase the amount of time you spend moving during every day. And you know, really one of the next steps is we want to combine this right? Because what happens sometimes, is people will engage in exercise, and they drop their lifestyle physical activity. Right. And it’s a compensatory response. Like I’m doing more here. So I have to save energy here. And we get it and we want to know well could we actually deliver an intervention where people start to exercise more and engage in lifestyle physical activity, and does that have a even greater benefits?

 

Véronique Gauthier-Simmons  14:47

But what about the body adapting so once you do more, the body adapts. So you still need to keep doing more and how far how many hours a day Oh, well, what is the limit?

 

Robert Motl  15:03

That’s a good question. You know, I don’t know that we know what the limit is, right? We have thresholds or ideas of how much people should increase to obtain benefits. So, for example, a person with MS, if they can get an extra 1500 steps per day, five days a week, that’s enough to have a meaningful effect on their physical activity levels. If they can get closer to 3000 steps per day, we see even greater benefits on there, multiple sclerosis, you know, but being cognizant that that, you know, there’s only a certain number of hours in the day, I think one of the things that we’re working on right now, is looking at how people take those steps during the day, right. So one of the things that we’re working on is this idea of step based metrics and looking at the speed at which you walk during every day tasks. And the idea being that we don’t necessarily have to have you do more than 1500 steps per day. But rather, if we can get you to do 30 minutes, over the course of the day, and each of those minutes be at a faster walking speed, that actually has greater benefits than accumulation. And that’s something that people can always bump up a little bit, right, like. So it’s complicated, it’s nuanced. And there’s no clear guidance right now on how much but I would say, shooting for 1500 steps per day over what you’re currently doing is good. Shooting for 3000 steps per day over what you’re currently doing is even better. Should you go past that. You know, just listen to your body, it will tell you whether that’s good or bad.

 

Overcoming MS  17:02

Have you signed up to the new Overcoming MS app? If not, download the live well hub in your app store and join the Overcoming MS community, get support, find connections and feel motivated to live well with MS. Download the live well hub today.

 

Véronique Gauthier-Simmons  17:20

And you’ve described before the exercise as a disease modifying behavior. So how does regular exercising compared to current DMT? Oh, can we or should we?

 

Robert Motl  17:39

That’s a very loaded question. You may have seen, we wrote this paper to the multiple sclerosis journal, we’re invited to make the argument that exercise is indeed a disease modifying behavior. And so what we did is we looked at how you establish medications as a disease modifying behavior. And they oftentimes focus on lesions, relapses progression of disability, as well as neuro performance outcomes like walking speed and cognitive processing speed. And so what we did is we adopted those same metrics and went and looked at the exercise literature. And to see if exercise, reduce those same measures of that we would use to approve a regulatory medication. And what we found is that exercise is associated with a lower burden of lesions. So the lesions are smaller and the number of lesions is lower. Exercise is associated with about a 27% reduction in relapse rates compared to control. And that’s important because that’s comparable to the very early classes of disease modifying therapies that were showing about a 25% reduction. Now, the newer classes are more powerful. We provided data that exercise is associated with a flat disability trajectory, whereas those who don’t exercise have an increase in disability. And the exercise is associated with beneficial effects in walking speed by the time 25 foot walk, and processing speed by the simple digit modalities tests. So this suggested to us that exercise indeed has disease modifying effects. Now, that should not mean that you should stop your disease modifying medication and replace it with exercise. What I think it means is that you should be on a really good disease modifying medication program that you develop with your neurologist and that you can add exercise on top of that, and expect there to be even more powerful benefits than just your disease modifying medication alone. You know, But there’s still a lot of questions to figure out in this, like, over a 10 year period of time what happens? Right, you know, because we still have this idea of smoldering MS and underlying, you know, low level inflammation that that, you know, maybe exercise helps with that. We got to figure that out.

 

Véronique Gauthier-Simmons  20:17

Yeah, actually, that’s what I was going to ask. MS is both degenerative and inflammatory. And do we know which part exercise influences?

 

Robert Motl  20:28

I guess I would say when we look at the evidence of exercise, and its effects on on kind of the common measures of inflammation that we, we obtained from blood draws, which are serum, and they don’t necessarily reflect what’s going on in the brain. We don’t really see a lot of effect of exercise on the serum biomarkers of inflammatory processes. When we look at exercise, and we look at serum biomarkers of of neurotrophic factors and neurotrophic factors are the biological factors associated with you know, loss of tissue like gray matter tissue and neurodegeneration, we do see that exercise is associated with an increase in particularly brain derived neurotrophic factor. And so that would be suggestive that exercise exerts more of an effect on neurodegeneration than it does on inflammation. The one thing that I want to really point out, though, is that in the studies, the majority of people are on a disease modifying therapy. And so that’s already suppressing the amount of neuro inflammation that you’re going to see. And so it may be hard to imagine the exercise could actually show an effect in the context of these medications. So I wouldn’t rule it out. I think we have to get better tools to understand neuro inflammation, and then apply exercise to to that paradigm to understand if there is a neuro inflammatory reduction with exercise training. And what about exercise in the brain? So I think you done research in this area as well.  So you know, a lot of what we’ve studied has has focused on different nuclei, or specific, you know, areas of the brain that are associated with with very specific functions. So for example, we focused on the thalamus as an area of the brain that’s associated with processing speed, and not just the volume of the thalamus, but how the thalamus is connected to other areas of the brain that are associated with cognition. We’ve also studied the basal ganglia, the basal ganglia are areas of the brain, the cognate, putamen, globus pallidus, that are associated with movement related patterns and also their connections to other areas of the brain. And what we’re showing in this literature is that exercise is associated with larger volumes of the thalamus of the basal ganglia structures, and is also associated with better connectivity. So these hubs of neurons that are very important for regulating cognition, or mobility, are developing stronger, better connections with other regions of the brain to form a better system for regulating cognition or regulating movement mobility. So we’re seeing these great changes, I would say, one of the most important studies in this area actually wasn’t done by our group, it was a group out of Italy, that studied balanced based training, and connectivity in the cerebellum. And they just show these really wonderful changes with balance training, suggesting improvements in balance. And that was really accounted for, by connectivity in the cerebellum, which is an area associated with balance and motor control. It just a really, really strong, well designed study. And so this is something that we focus on every day now in our labs is trying to understand exercise in the brain, because I think for two reasons. One is I think people with MS want to know more like can I exercise and help restore brain and prevent brain loss. And I think that neurologists and other health care providers, they really want those data to show that exercise is doing something within the brain. So they can say, hey, just an exercise not just for your fatigue or your depression, but also exercise because it will help to produce brain health, you know, improve the structure function of the central nervous system.

 

Véronique Gauthier-Simmons  24:54

You said last year that exercise activates the central nervous system, the parasympathetic nervous system, the endocrine system, the skeletal muscle system, the cardiovascular system, and it does so in a very integrative and systematic manner. And by repeatedly exposing yourself to bouts of exercise, all of these systems adapt in an integrated manner. They learn how to work better, they grow stronger, they grow better. And I think as a person living with MS, this is what I need to know, in a way that when I exercise, everything is improving. So in a way, the details you work on it, and you can explain, but it’s just nice to remember everything is going to be better with exercise. But are they some people with MS. Who don’t benefit from exercise? Or maybe benefit less?

 

Robert Motl  25:50

Yeah, that’s a great question. I’m glad you found that quote, because that is something that we live and breathe by that this notion that exercise is the only stimulus that activates every system in the human body in a systematic, integrative organized way. And literally, every time you activate it, it’s a stressor to those systems. And those systems in response to stress, learn how to adapt and work better together. And that is just the beauty of exercise. There’s nothing else like that. When I think about like, does exercise benefit everybody equally? So that’s getting into this whole idea that we’ve been working on lately called response heterogeneity. That is, if I if I give 10 people the exact same exercise prescription, will all attend show the exact same adaptations? And the answer that we’re learning is no. Okay? That is that some people with with a stimulus will maybe show a little bit of worsening, some people will show no change. And some people will show great adaptations or benefits. So one of the keys in this is learning how to create precision based prescriptions for people with multiple sclerosis. And what that relies upon is trying to understand characteristics of people with MS, and how those characteristics portend, how they might respond to one program versus another program. And make sure that we match the program optimized based on those characteristics. That’s like the Holy Grail that we’re working on over the next 10 years. And and it’s really complicated, it’s the same thing that’s happened if I can for a second in the world of of cancer, and medications for cancer is that they used to have this kind of one size fits all approach where you have cancer, we’re going to do this medication. And then they saw that some people get better, some people don’t change, some people get worse. And then they’ve started to identify these biomarkers that say, Oh, if you have this biomarker, we’re going to give you this medication, because everybody who has this biomarker and receives it gets better. And that’s what we have to do with exercise, and MS is figure out those biomarkers.

 

Véronique Gauthier-Simmons  28:26

So that’s how you see the future of exercise therapy. So who do you think would be in charge of prescribing this? Do you think the neurologist or the GP would need to be involved?

 

Robert Motl  28:42

That’s like a 10 hour discussion. So this has been something that we’ve been working on quite a bit is trying to understand the promotion pathway. And so we started about 10 years ago asking people with MS who they want their exercise prescription guidance promotion from and, you know, to my chagrin, they told me, neurologists and they were very clear that it wasn’t like a kinesiologist exercise professional such as myself, they really said neurologist, and then you know as we pressed them a little further than they they opened up to well, maybe the nurse practitioner or you know other other professional and the neurologists office, then maybe the PT and OT and then lastly someone like yourself. So you know, like then the next question we went to as we went to the healthcare providers, particularly the neurologists, and said, What do you think? Do you think you’re the right agent of change? And they said, Yeah, absolutely. We can promote exercise. We just don’t know what to tell people. Right? And the nurse said the same thing. PTs and OTs have more information to tell people but they’re still not 100% equipped with with the exercise prescription because you know, PTs and OTs it’s really a clinical practice to restore function through very specific movement based systems and parameters. And it’s not a more globalized thing like helping individuals engage in exercise. So so what we learned, if you will, is that there’s this convergence, people with MS want the health care providers, particularly the neurologist, the neurologists are willing to do it. But we have to create the knowledge base and the system for this dialogue, this interaction, and everything. So we’re working on that right now. That’s something that some of my my colleagues are working on, is developing these kinds of scripts and trainings and things along those lines. The one thing that we do have that’s already ready to go is, we already have the toolkit. So both the neurologist and the patient said, I need a toolkit, like you gotta give me something that I can go exercise with. We’ve created that, and we have the full program to go with it. That’s done. Now we have to figure out how to get people to that point.

 

Véronique Gauthier-Simmons  31:05

So your your latest study, I think, is on the mood and the exercise training study for MS. Yep. So can you tell us about that a little bit?

 

Robert Motl  31:16

Yeah, absolutely. It’s one of the most important studies we’re doing right now. And so what we realized when we looked at the literature on exercise, and depression and people with MS is that there wasn’t a single study that actually recruited people with major depressive disorder. So people have a clinical diagnosis of depression. And so we wrote a grant to the Department of Defense in the United States, which sounds odd, but they have a congressionally mandated research program that funds research for diseases like MS. And they funded this study, to deliver exercise training as a way to treat depression in people with MS who have major depressive disorder. And so we work very hard with our neurologists in Chicagoland area and a little bit beyond to identify people with MS who likely meet criteria for having major depressive disorder, we do very extensive screening to make sure that they meet clinical criteria for major depressive disorder, we then bring them into the lab and do a lot of testing with them. Mood testing, cognitive testing, other symptoms, fitness, you know, the whole baseline gamut. And then we give them one of two evidence based programs. And they do these programs at home. But we support them remotely through coaching from our lab, one of the programs is structured aerobic and resistance exercise that they do three days per week. And they progressively move from a very light, short duration, up to meeting guidelines within six to 10 weeks. And then they maintain that over the remainder of the 16 week period. The other protocol is range of motion. So one of the things that we find is that people with MS are very tight and restricted, and they lose range of motion. And that has all sorts of secondary complications. So we focus on that as another modality and we have a program, we give them all the equipment they need. We give them manuals, we give them, the logbooks, calendar has everything they need, and then we coach them remotely. So one day a week, they get on a Zoom with our behavioral coaches who are amazing people really highly trained to work with them on their exercise program. They’re their behavior change and sticking with it and adherence and compliance. And so we’re examining how all those baseline parameters change after the intervention. And then we follow these people up for months afterwards as well, where we’ve stopped giving them coaching, but they still have all the materials and we’re hoping that they’re still doing it. And what we hope to demonstrate is that these programs are effective for reducing depression in individuals with major depressive disorder who have MS. And if so, this would provide the first class one evidence that exercise could be prescribed for treating depression and MS. And that would be a game changer of a study.

 

Véronique Gauthier-Simmons  34:31

That’s brilliant. And I saw on the website of the exercise neuroscience research laboratory that there are so many different projects going on. Could some of our listeners volunteer on this program if they qualify?

 

Robert Motl  34:54

Yeah, you know, we we study lots of different things. I mean, some days I wonder how we do it all, but we do a lot. And our lab is very big, we have lots of dedicated people. And so yes, if if you can connect people to our lab, if they, if they go to Google and type in University of Illinois at Chicago and exercise neuroscience research lab, they’ll find us. And there’s a link on there for research projects. And, you know, we’ve purposely designed these projects to be things that anybody, anywhere in the United States or the world for that matter, could participate in. Because, you know, we really one of our missions is to create a global movement of exercise and MS. And, particularly, because when you look at what’s been done, it’s largely done and in large, industrialized countries, and, and there’s lots that a lot of people who are in places that need this evidence, and so we’re trying to create that as well. But that’s a side point.

 

Véronique Gauthier-Simmons  35:59

Thank you so much. Again, thank you for all your work. Is there anything else that you would like to to add to this conversation? Anything else that you would like to share?

 

Robert Motl  36:15

Yeah, I think that we’re learning more and more every day that living your best life involves doing things like exercising, eating well, diet, lifestyle. And so I would encourage people that it doesn’t have to be exercise, but exercise is probably the most potent of these agents. But as you start to change your exercise behavior, think about doing some other things like maybe trying different ways of eating and things along those lines and, and trying to get a little bit better sleep quality. And I think it’s the totality of those things that will really make the biggest difference in the end, but exercise first,

 

Véronique Gauthier-Simmons  36:56

You are describing the Overcoming MS program that is actually holistic and includes exercise and stress management and diet and mindfulness. And so, yeah, it’s a whole new lifestyle. Thank you so much. That’s very motivating. And I wish you a wonderful rest of the day. Thank you so much for talking to me. Thank you.

 

Robert Motl  37:20

Thank you.

 

Overcoming MS  37:23

Thank you for listening to this episode of Living Well with MS. Please check out this episode’s show notes at overcoming ms.org/podcast you’ll find useful links and bonus information there. Don’t forget to subscribe to the podcast so you never miss an episode. And please rate and review the show to help others find us. This show is made possible by the Overcoming MS community. Our theme music is by Claire and Nev Dean, our host is Geoff Allix. Our videos are edited by Lorna Greenwood, and I’m the producer Regina Beech. Have questions or ideas to share? Email us at podcast at overcoming ms.org We’d love to hear from you. The Living Well with MS podcast is for private non commercial use and exists to educate and inspire our community of listeners. We do not offer medical advice for medical advice please contact your doctor or other licensed health care professional.