Northwestern University’s Daniel Corcos is testing whether high-intensity aerobic exercise can slow Parkinson’s progression in the Phase 3 SPARX clinical trial.
Exercise can improve Parkinson’s symptoms, but could it also slow the disease’s progression? Northwestern University researcher Daniel Corcos, PhD, is leading a Phase 3 clinical trial (SPARX3) to test whether high-intensity aerobic exercise can slow Parkinson’s progression, particularly in people who are newly diagnosed and not yet taking Parkinson’s medication.
Corcos, a professor at Northwestern’s Department of Physical Therapy and Human Movement Sciences, studies how targeted exercise affects movement and brain function in Parkinson’s. His team has completed clinical trials examining both progressive resistance training and endurance exercise in Parkinson’s. The large follow-up trial designed to answer whether the intensity of exercise can change the trajectory of the disease.
In this conversation with Being Patient founder Deborah Kan, Corcos lays out a practical, four-part “exercise prescription” for Parkinson’s — aerobic training, resistance work, flexibility, and balance-focused neuromotor training — and explains how to tailor it based on symptoms and stage of disease. He also unpacks how SPARX3 will compare 370 people assigned to moderate- versus high-intensity treadmill workouts over two years, tracking changes in Parkinson’s symptoms and brain scans to see whether higher-intensity exercise is linked to slower disease progression.
Being Patient: What does it mean to exercise when you have Parkinson’s?
Daniel Corcos: Well, to have Parkinson’s, first of all, it’s very important to get an accurate diagnosis. In the case of Parkinson’s disease, the people who see people with Parkinson’s disease are movement disorder specialists. Several other diseases can look a little bit like Parkinson’s disease at the beginning. People often have essential tremor, and sometimes one can have both Parkinson’s disease and essential tremor. So the first point is to have an accurate diagnosis which you can be reasonably confident in. One is never fully confident because there is no definitive diagnosis while you are alive.
We’ve been studying exercise for a long time, and we’ve been studying exercise in Parkinson’s disease since the early ’90s, and we know a lot. We know very clearly what is good for you and we know clearly why it is good for you. The exercise prescription [was] published in 2024. The details are also on the Parkinson Foundation website.
The first thing is that all of us have a heart. It’s good to look after your heart. You will have heard exercise for your heart and lungs referred to as cardio, aerobic, and endurance. They’re all roughly synonyms. And what you should be doing is exercising four times a week for about 30 minutes, with your heart rate elevated to about 80-85 percent of your peak heart rate. You warm up for a few minutes, you cool down for a few minutes.
And that is especially valuable for those of you who have young-onset Parkinson’s disease, because the younger you are, the longer you navigate the disease. And there is cumulative evidence now from four studies that if you exercise like that, there’s a high probability you will slow the rate of your disease progression.
Being Patient: Is that directly associated with dopamine signaling, motor circles? What do we know specifically about why exercise is good, especially at that earlier stage, in terms of the biological mechanisms that it may be having an influence on?
Corcos: The precise underlying mechanisms regarding how it works, they’re still to be elucidated. My own view is that when you’re exercising at a high heart rate, you are pumping a lot of blood through the system. The blood is going to the brain. Every decade that we age, we get less blood to the brain. Less blood to the brain is less nutrients to neurons. Less nutrients to neurons is neurons not working as well. There is evidence that dopamine uptake in neurons is better after high-intensity exercise. So this is the cardio, aerobic, endurance.
Part two of the exercise is resistance exercise, weightlifting. It’s very good for osteoporosis. It’s very good for preventing frailty. Clear data, it improves cognition. It’s very important.
Third part of the exercise prescription is that many of you will wake up in the morning and you may feel a little bit stiff. Some of you may feel [really] stiff. And so getting going in the morning is hard. Flexibility training, flexibility exercises, is very good for stiffness.
The final part of the prescription is as the disease progresses, the probability of falling goes up, the probability of hesitating when you initiate gait goes up, the probability of freezing of gait goes up. So you need what is called neuromotor training, which is essentially balance exercises. These are best done under a certain level of supervision so somebody can show you what to do. You can think of it as agility training. Activities like dance are very good. But the idea is you put your body in a position where your balance is tested, and that helps you. So those are the four parts of the prescription. They’re clearly known, and the benefit is overwhelming.
Being Patient: You’re conducting a Phase 3 trial right now, and you mentioned several other trials that have delved into exercise and Parkinson’s. Clinically, what differences do you see between patients who exercise regularly and those who don’t with Parkinson’s?
Corcos: I think most of my colleagues who see patients on a daily basis — I’m a PhD, but I do spend a lot of time with people with disease — most of my colleagues say that the patients who exercise and live a healthy lifestyle are doing much better. There are lots of studies which have looked at the epidemiology, if you like, of how disease progresses and compared people who exercise with a healthy lifestyle, and rates of progression are slower. I think there’s no question.
I [meet] every month with a group of people. They’re all firm converts to exercise, and they all view it as medicine. From their point of view, exercise is medicine. And this has been argued for quite a long while. And so those people do better. I think people who stay at home all the time, who don’t go out and socialize and move and are active with people, they just don’t do as well.
It’s important for you all to realize, this has got nothing to do with Parkinson’s disease per se. This is true across the spectrum, from Alzheimer’s to people who’ve had a stroke to people who’ve got metabolic syndrome to people who have diabetes. The take-home message is the same.
The thing about Parkinson’s disease is that exercise does mobilize dopamine from within, the endogenous use of dopamine, and therefore it’s a disease tailor-made for almost an extra benefit from exercise.
“And there is cumulative evidence now from four studies that if you exercise like that, there’s a high probability you will slow the rate of your disease progression.”
Being Patient: You had mentioned earlier it’s especially beneficial for people with early-onset Parkinson’s. Is that because exercise can actually change the disease process itself, or is it helping the brain kind of compensate for damage? What do we know exactly why that is in terms of the relationship with the disease? Is it cause-effect? What is it?
Daniel Corcos: A lot of what goes on when you adopt a healthy lifestyle is you do learn to compensate. And so that is certainly true. The reason I stressed the early onset is if you have a disease for 10 years, you get a 10-year benefit from exercise. I know people who are 28. You’ve all heard of Michael J. Fox. He was 29. So he’s had a disease for 40 years. So in a sense, you’re getting four times the benefit, but that’s just because you have the disease four times as long. And so the earlier you get the disease, the greater the benefit over one’s life.
And so the way that I look at this is I try very hard to help people understand that just because you have Parkinson’s disease doesn’t mean you can’t be healthy. There’s nothing about having Parkinson’s disease per se which stops you, especially when you get it early on and you’re still young, from leading a relatively normal, healthy lifestyle.
Now, I’m fully aware some of you may be in your 80s, and some of you may be what is called stage three and four. And I’m fully aware of how you present, and that life can get very complicated, and I’m not trying to underplay that. But I do want to put [out] a message of informed optimism, especially for those of you who are just newly diagnosed. Much of what you read, much of what you hear can be a little bit pessimistic. I think the way to approach the disease is with informed optimism.
Being Patient: A viewer is asking, is there a specific exercise that’s more beneficial than others? Between running, walking versus weightlifting, or yoga — have different types of exercises been studied in terms of the benefit to people with Parkinson’s?
Corcos: A little bit like asking the question, is French cuisine better for you than Greek cuisine, or Italian cuisine? I’m not convinced that’s the best question. I think you have to start off with yourself. So if you’re younger onset, if you’re not falling, if you’re not freezing, then putting the time in on slowing disease progression is where I would focus. Because one of the things I’m always told is, you’ve got all these things to do, and there are only so many hours in the day, and I’m a very busy person.
If I was falling, then I would go very, very much on the neuromotor. I would find a physical therapist. I would do Rock Steady Boxing; that’s a form of boxing. So if I had a balance agility problem, I would probably put more time on that.
For those of you who are noticeably older, and you’re having trouble getting out of a chair, then I would be doing a lot of exercises just to maintain my everyday activities of daily living. And I would work very closely with a PT. So the classic answer to all questions always is, it depends.
Being Patient: I want to talk a little bit about the trial that you’re running right now. It’s in Phase 3. It’s called SPARX3, and it’s to test whether high-intensity aerobic exercise can slow Parkinson’s progression, particularly in people who are newly diagnosed and not on medications. Tell us how many people are in this trial? Do you have any early insights on what exactly we’ll learn once you’ve completed this study?
Corcos: We will randomize 370 people. One hundred eighty-five will be 60-65 percent peak heart rate. One hundred eighty-five will be 80-85 percent peak heart rate. The study is over two years, and at the end of the day, we expect to show that the group exercising with a high heart rate, 80-85 percent, will have slower progression of the disease than the other one. So when you look at the difference between a measure of Parkinsonism, the group at 60-65 percent will have a higher number there. It’s called the Movement Disorder Society Unified Parkinson’s Disease Rating Scale, and that number will be higher in the moderate-intensity group.
We also have a scan. It’s called a dopamine transporter scan. It looks at how dopamine binds in different parts of the brain. And we expect that the binding potential to be higher in the group that exercises at 80-85 percent.
In Europe, the standard drug for Parkinson’s disease is called Madopar. For those of you who are American, you probably know it as Sinemet. Going on dopaminergic therapy is now currently thought of as good. There used to be an idea that trying to delay it — and for those of you, and I’m in this camp myself, who try to avoid drugs as often as possible — there is the idea that maybe, “I can get away with [delaying] it.’ Well, current guidelines from the American Academy of Neurology is to take your dopaminergic medication.
In fact, in our exercise prescription, which was written by three young movement disorder specialists, we make the case that one way to look at your medication is in order to exercise.
We have another paper out for those of you who love to run. If you end up with running-induced dystonia, which for young people can be real aggravation, one way to deal with that is extra medication. And Madopar happens to be particularly effective. And so medication is good.
Why is SPARX3 on people who are drug naive? We want to look at Parkinson’s disease and how exercise affects Parkinson’s disease in the absence of drug therapy. SPARX2, which was published in 2018, and which was very informative, was on drug-naive people. So anytime you read studies of disease progression, they will always be — I think I can say always quite emphatically — on people who have not yet taken medication. Otherwise, you don’t know whether it’s your new treatment or the medication which is altering disease progression.
“I [meet] every month with a group of people. They’re all firm converts to exercise, and they all view it as medicine. From their point of view, exercise is medicine.”
Being Patient: When will we have the results of this study? And I’m assuming you’re not recruiting anymore, right?
Daniel Montie Corcos: We’ve got 16 more to randomized. So at about 11 of our sites, we are recruiting very vigorously. We expect to publish the paper in the New England Journal of Medicine in the middle of 2029. That’s our target journal because it’s a target journal for all Phase 3 clinical trials.
Being Patient: What exactly is the rigorous exercise that participants are undertaking?
Corcos: They’re all on a treadmill. That was done intentionally. For those of you who are exercising, it doesn’t have to be a treadmill. It can be biking. It can be walking. It can be elliptical. It can be whatever you want. Heart rate is very tightly controlled. It’s measured with a heart rate monitor. So it’s five minutes to warm up, 30 minutes at the heart rate of 80-85 percent, precisely measured, and five minutes to cool down, precisely measured. So that part of the study is very rigorous.
We also monitor people’s activity for a whole week during the course of the study. Every three months we monitor it for a week, because we’re interested in the question: If you’re now getting fitter and fitter and you’re exercising, there are three possibilities. One, your overall activity level doesn’t change. Two, you’re now fitter, so you go out and do more. And we saw a lot of that in SPARX2. Third option is you’re so tired from your exercise that you hit the couch. So your overall activity level could even drop. And we have that data.
Being Patient: For people who are watching right now, just incorporate some sort of exercise in your life. We’re definitely seeing the benefits. I can feel it when I run. I really feel that a lot changes. My memory gets better. My concentration is better during the day. So that natural link between the benefits for your brain and exercise isn’t such an anomaly, I think.
Corcos: It’s very important to think of exercise from two totally separate points of view, one of which is over the course of your life. So you exercise — are you slowing disease progression? Are you maintaining healthspan? Are you turning yourself into a super-ager, which is what is quite necessary.
The other thing, which is equally important but much less studied, is what effect does it have on you day to day? And I call this the acute exercise effect. So I have a friend just like Deborah. I’m going to paraphrase your moods here; I could be wrong. If Deborah goes two or three days without her run, she might get a little bit cranky. Her patience, her concentration, her focus might drop. And so for people who really get a benefit, you should ask yourself, am I getting an acute effect?
And we’re going to be looking at this in SPARX3. There is something about the different biomarkers in the blood that may respond differently for some people. Not everybody gets that kind of endorphin high. For those who do, it’s terrific. And when they’re deprived, this is not good for their family.
If any of you struggle with exercise, think of the benefits you get on a day-to-day basis. Think of the benefits you’re going to get in three months or three years. And if none of that works for you, you can take it to the bank that the better your physical function and cognition is, the better it is for the people around you.
So when I write grants, I can use the number: there’s more than a million people with Parkinson’s disease in America — and yes, most of my colleagues do that. I actually don’t. I make the case that every person with Parkinson’s disease probably has a family and friends of 10 to 20 to 30 people who, in some way, are affected. So anything you can do to maintain your health span is really good for you, your family and your good friends.
