Placebos Vs Parkinson's: The Power Of Joy : Short Wave Parkinson's disease is a brain disorder that leads to difficulty with walking, balance and coordination. There is currently no cure, but scientists in Pittsburgh, PA have an ambitious plan to develop a treatment based on the placebo effect. NPR science correspondent, Jon Hamilton, tells the story of how this plan came to be. It involves a batch of illegal drugs, the rabies virus, and figuring out what makes a monkey really happy.

Watch the video of the cyclist with Parkinson's disease here: https://bit.ly/3GPZ6PK

Email the show at ShortWave@NPR.org.

Placebos Vs Parkinson's: The Power Of Joy

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EMILY KWONG, BYLINE: You're listening to SHORT WAVE...

(SOUNDBITE OF MUSIC)

KWONG: ...From NPR.

DAN CHARLES, HOST:

Hello, Short Wavers. Dan Charles here. You've heard of placebos - right? - little sugar pills. Well, apparently they can have profound effects, sometimes even get our brains working differently and help treat a disease or disorder. This is what I've been hearing from NPR's resident brainophile, Jon Hamilton. Hi, Jon.

JON HAMILTON, BYLINE: Hey, Dan. You know, I have been pestering you about this because it's true. In some cases, these fake drugs can cause real changes in the brain. And I've been talking to these scientists in Pittsburgh who think they might be able to use this placebo effect to come up with better treatments for Parkinson's disease.

CHARLES: Really? So how does a placebo actually help somebody with Parkinson's?

HAMILTON: To answer that, let me tell you about this couple I met while I was in Pittsburgh. They asked me not to use their last name to keep their medical situation private, so I'll just use their first names, Paul (ph) and Roz (ph).

CHARLES: OK.

HAMILTON: Anyway, Paul has had Parkinson's for more than a decade. You can tell. He moves slowly; he has some tremor; his balance is a bit off. So for Paul, something as simple as getting out of a chair usually takes some time and effort, but not always. Paul and Roz told me the story about something that happened to them while they were taking care of their grandchildren.

ROZ: One grandson was running towards the steps to go downstairs.

PAUL: Out of the corner of my eye, I could see this little figure moving.

ROZ: Paul jumped up from the chair and ran to my grandson.

PAUL: Not thinking about how to get up, just get up and go.

ROZ: I mean, he just got up like it was nothing and ran to pick up Max (ph). He goes, Max, come here. He picks up Max.

CHARLES: So the effects of Parkinson's just kind of disappeared when he realized he had to save his grandson.

HAMILTON: Right.

CHARLES: How does that work?

HAMILTON: No one knows exactly, but it appears to be some variation of the placebo effect. Instead of a sugar pill, though, it seems to be a particular situation that has made the difference. The fancy name for what Paul did is paradoxical kinesia. This is something that tends to show up in people with Parkinson's when they're feeling stress or a really strong emotion. It's like the brain is suddenly able to flip a switch that temporarily allows them to move the way they used to.

CHARLES: But is there some way to control this paradoxical kinesia and use it to help people with Parkinson's?

HAMILTON: I mean, it's a big leap, obviously. But these scientists in Pittsburgh - they have a really ambitious plan to develop a treatment based on the placebo effect. This plan also has a pretty wild back story. It involves a bad batch of illegal drugs, the rabies virus and figuring out what makes a monkey really happy.

CHARLES: Today on SHORT WAVE, placebos versus Parkinson's.

HAMILTON: And the healing power of joy - really.

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CHARLES: OK, Jon, first of all, how do we treat Parkinson's right now? Can we even?

HAMILTON: So Parkinson's is a disease that causes cells to become impaired or die in a part of the brain called the basal ganglia. This area controls movement and, as the disease progresses, people's movements tend to become slower, stiffer, less coordinated. Sometimes they freeze up. Their hands often tremble. Their voice may quaver. Ultimately, they may be unable to walk and talk and even feed themselves.

CHARLES: It's a really hard disease.

HAMILTON: It is. And right now, there is no cure. But there are treatments that relieve some of the symptoms. The drug L-dopa, for instance, can replace a substance called dopamine that the brain is no longer making. L-dopa works really well at first. But over time, it can become less effective and produce more side effects like involuntary movements. As a result, many patients turn to deep brain stimulation, but that requires brain surgery and running wires to a sort of pacemaker device implanted in your chest that eventually will need to be replaced. So there is definitely room for some new options.

CHARLES: I've read that exercise can help. Is that true?

HAMILTON: It appears to, especially exercise that focuses on balance and coordination. Also, there is a lot of evidence that exercise can provide psychological benefits.

CHARLES: OK. But as you said, nothing close to a cure. So this placebo idea - where did that come from?

HAMILTON: It came mostly from a guy named Peter Strick. He's a professor at the University of Pittsburgh and also runs the Brain Institute there - a big deal, right? He's known as someone who follows his curiosity and likes to take on big challenges. So here's what he told me about the placebo effect.

PETER STRICK: I love it when people say it's all in your head because your brain is in your head.

CHARLES: I think I understand. So he's saying if the placebo is having an effect in your head somewhere, it's actually affecting brain circuitry.

HAMILTON: Exactly. He's saying that the brain can change its own circuits and that this can help treat a disease.

STRICK: And there are, I think, concrete neural circuits that explain placebo effects. There are real biological underpinnings for these kinds of things.

HAMILTON: So Strick heard about Paul leaping out of his chair to grab his grandson. He thought it sounded like a classic example of paradoxical kinesia. And he told me it reminded him of this video that has just fascinated him. This video was made back in 2010 by two neurologists in the Netherlands. Strick showed it to me, and now, Dan, I am going to show it to you.

CHARLES: I would love to see this.

HAMILTON: All right. Let's roll this. So we're in a hospital - in a hospital corridor, and we're watching this man get out of a wheelchair, right?

CHARLES: Yeah, yeah. He looks very unsteady. His hands are shaking.

HAMILTON: Arms down at his side - classic Parkinson's. There's an attendant who's making sure he doesn't hurt himself.

CHARLES: Ooh, he's kind of going down on his knees here.

HAMILTON: Yeah, that's a test they do to see whether - if your gait is interrupted, whether you can recover, and he can't. He goes down to his knees, right?

CHARLES: Now the scene changes.

HAMILTON: Yep. We're out in the hospital parking lot. He's just gotten on a bike and ridden away as if...

CHARLES: He's biking down the street.

HAMILTON: Yeah. I mean, it's - right. It's like he's on his way to work. No problem, guys. And what's even more amazing to me is that he's not just pedaling automatically, he's reacting to what's around him.

CHARLES: Ooh, nice turn.

HAMILTON: Right? I mean, he looks great.

CHARLES: Yeah.

HAMILTON: You would - like, you saw that guy coming down the street, you would never know he had Parkinson's.

CHARLES: No, not in a million years.

So this is kind of like that situation you described with Paul leaping out of his chair to grab his grandson, right? But this man in the video is not responding to fear.

HAMILTON: No, clearly not. And that's part of what fascinated Peter Strick. He thinks some other emotion was involved, perhaps joy - you know, the joy of being able to move again, of being on a bike, of being in control.

CHARLES: Well, I can totally relate to this. I mean, there are days when there's nothing I would rather do than get on my bike and go for a ride.

HAMILTON: Me, too. I mean, it makes you feel good. So in any case, Strick wanted to know what switch had been flipped in this guy's brain. His lab has been working to identify the brain circuits that are involved in voluntary movement, and here is where rabies comes in.

CHARLES: Rabies?

HAMILTON: Rabies. The rabies virus has this amazing and kind of terrifying ability to infect a nerve cell anywhere in the body and then follow the nerve pathways that lead back to the brain. Strick was one of the scientists who developed ways to use the rabies virus to trace the brain circuits that allow animals to move. That helped him figure out which circuits are damaged in Parkinson's disease. It also helped him identify circuits that seem to be involved in both movement and emotion. All of that research helped Strick's lab come up with this hunch about what's going on in the brain of that Dutch cyclist who clearly has damage to a critical brain circuit.

STRICK: Our hypothesis is that there's another circuit that's intact, and it's engaged by our sense of reward, by the joy of doing something and that this circuit isn't affected in Parkinson's disease.

CHARLES: So he's saying the key is how to activate this alternate circuit...

HAMILTON: Right.

CHARLES: ...That is not damaged that can kind of take over that we see maybe happening in that video of the Dutch cyclist.

HAMILTON: Exactly.

CHARLES: This sounds like an amazing hypothesis. But, you know, hypothesis is just a fancy word for unproven hunch, right (laughter)?

HAMILTON: (Laughter) Yeah.

CHARLES: Is there a way to test it and figure out if it's true?

HAMILTON: Strick thinks there is. He has put together this big effort to do just that, and he's raised $12 million to pay for it. It comes from a group called the Aligning Science Across Parkinson's Initiative.

CHARLES: That sounds like a lot of money. How are they going to spend it?

HAMILTON: They divided the project into parts. So for example, a lab run by Rob Turner at the University of Pittsburgh - they'll be studying a version of Parkinson's that happens in monkeys, whose brains are a lot like ours. You really can't do this in rats or mice. Turner told me this sort of study is possible because of something really tragic that happened in the early 1980s. It involved people in San Francisco who were buying street drugs.

CHARLES: I think I remember something about that. They were getting something that turned out to be poisonous, right?

HAMILTON: Yeah, yeah. Relatively young people started turning up in the emergency rooms with symptoms that looked exactly like Parkinson's disease. Turner says, at first, it was a complete mystery.

ROB TURNER: One of the local neurologists did the detective work, and he discovered that someone had botched a batch of synthetic opioids and made a neurotoxin instead.

HAMILTON: That neurotoxin is called MPTP. And if you give small doses to monkeys, they develop something very much like Parkinson's. So Turner's job in this big project is to study how this induced version of Parkinson's gradually impairs one specific brain circuit in these animals. Then he's going to try to use the placebo effect to flip on this other circuit that's still intact.

CHARLES: So wait. Monkeys can actually experience a placebo effect? How would you actually do that?

HAMILTON: Well, Turner is pretty sure that monkeys can. He thinks that if these monkeys feel the sort of joy that some people get from riding a bike, say, they will demonstrate this thing, paradoxical kinesia - you know, that flip of a switch in their brain that allows them to move quickly and easily again.

CHARLES: (Laughter) Does Turner know what gives monkeys joy?

HAMILTON: Well, (laughter) he has some ideas. Monkeys love to eat, and they will do all kinds of things to get even a pretty ordinary reward - you know, something like fruit juice. Just anticipating that sort of reward releases all kinds of feel-good hormones in a monkey's brain. So Turner is hoping that the prospect of getting some really special treat will flip the joy switch. He's thinking, you know, maybe something like a tropic smoothie.

TURNER: Not just the normal small size tropic smoothie, but the monkey's going to get that - yes, right? This worked. Get that kind of reward.

HAMILTON: And the scientists will be watching the activity and the dopamine levels in the monkey's brain while this happens. What they hope is that they will actually see the switch flip in the brain circuit that allows normal movement. And once you know which circuit is the key, it should be possible to turn it on through other means, you know, like electrical stimulation or even gene therapy.

CHARLES: OK - so to create that phenomenon that we watched on that video in the monkeys who are suffering from this version of Parkinson's. It does sound like a long way off, though. What about people who have Parkinson's now?

HAMILTON: It turns out there are a lot of ways to get the placebo effect. So for example, many Parkinson's patients who have trouble walking, they're able to dance. So there are all of these dance classes just for people with Parkinson's. And dancing can sometimes help them move better, perhaps in part because of the placebo effect. And remember Paul, you know, the guy who rescued his grandson? He's found another activity that seems to help him move better.

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RICH MUSHINSKY: One, two - one, two.

HAMILTON: So Paul goes to this gym called the Fit4Boxing Club in the suburb of Pittsburgh.

CHARLES: Boxing.

HAMILTON: Boxing, you got it. And the guy you heard calling the punches and those combinations - that's Rich Mushinsky. He owns the club. And he told me that a boxing workout is really a great option for people with Parkinson's. It's all about footwork and balance and coordination, and it's also about spending time with a group of people who are facing the same challenge you are. Plus, Mushinsky says, it makes people like Paul really happy.

MUSHINSKY: It's not a cure, but it makes it better for a short period of time. And, you know, the fighters will tell you how it makes them feel, and we can tell how much better they're doing.

CHARLES: Wow. Does Paul think his boxing classes are helping?

HAMILTON: He told me that they are. And he says it helps him move like a cat.

CHARLES: Amazing. Joy, maybe, solution to Parkinson's.

HAMILTON: Maybe, Dan.

CHARLES: Thank you so much, Jon.

HAMILTON: Thanks, Dan.

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CHARLES: This episode was produced by Eva Tesfaye and edited by Stephanie O'Neill. Katherine Sypher checked the facts. Stu Rushfield was the audio engineer. I'm Dan Charles. Thanks for listening to SHORT WAVE from NPR.

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