Teasing Apart The Causes And Early Signs Of Parkinson’s

Some Parkinson’s patients may experience strange symptoms, like smell loss and sleep disorders, decades before diagnosis.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Ira Flatow?

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• 0:16Speaker 01

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• 0:33Flora Lichtman?

  Hey there. This is Flora Lixman, and you're listening to Science Friday. Each year, around 90,000 people in the US are diagnosed with Parkinson's disease. It's a neurodegenerative disease that can cause tremors and affect cognition. Scientists think that Parkinson's happens when some neurons, cells in the brain, get clogged up with clumps of protein and stop working right. Now, normally, proteins aren't a problem. They're good. We need them. But when certain proteins misbehave and fold into weird shapes, trouble can start. Misfolding proteins are found in lots of neurodegenerative diseases like ALS and Huntington's disease and Alzheimer's. You've probably heard about plaques and tangles. Those are the protein clumps found in Alzheimer's.

• 1:18Flora Lichtman?

  In Parkinson's, a protein called alpha cyanuclein is thought to be the culprit, misfolding, clumping, and spreading through the brain. So what gets this protein ball rolling? And can it be stopped? That is what we're talking about today. Let me introduce my guests. Dr. Emily Temin Donfar is a neurologist specializing in movement disorders. She's a clinical assistant professor of neurology at the Keck School of Medicine of USC. And Dr. Michael Okun is a professor and executive director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health. He's also the medical advisor for the Parkinson's Foundation, and he's written many books about Parkinson's. His latest is called "The Parkinson's Plan: A New Path to Prevention and Treatment."

• 2:03Flora Lichtman?

  Emily and Michael, welcome to Science Friday.

• 2:05Speaker 03

  I should be here.

• 2:06Flora Lichtman?

  Thank you for having me. Michael, did I get that description right about the misfolded proteins causing problems?

• 2:13Speaker 03

  Yeah, so these proteins exist normally. And so when we have something called alpha synuclein, you know, you need these things and they they're important for regulation and for what we call homeostasis. And so when we think about, you know, Parkinson's and Alzheimer's disease and ALS and these diseases that are degenerative, we think about them showing up in protein folding. It's a clue, it's a breadcrumb that's telling us something is going on in this brain, in this body that is evoking, it's causing the body to have a response to say, hey, you're out of homeostasis. But what we have to be careful of is we have to be careful

• 2:58Speaker 03

  of the enticing idea that it's all that these protein clumps that they're that they're the cause of everything. We have to be very careful of going down that road, you know, too far, because it might be that this is just a signal and a very important signal. But but I think we have to be really careful to ask ourselves, why does it start? Why does it spread? Why does it progress? And to be humble and say, we really don't have the answers to those questions yet.

• 3:28Flora Lichtman?

  Emily, I think people are familiar with some of the later stage symptoms, tremors, impaired movement, in some cases cognitive impairment. But you are studying some very early signs of Parkinson's. And I know smell is one of them. What do we know about this?

• 3:45Speaker 04

  Yeah, so there's a very large observational study going on and it's been going on since 2010 called the Parkinson's Progression Marker Initiative. And this study is including participants who have Parkinson's disease and those who are at risk of Parkinson's disease, what we call a prodromal participants. And these are people who have diminished sense of smell, what we call hypozmia, which we think often predates motor symptoms like stiffness, slowness and tremor, as you mentioned.

• 4:21Speaker 04

  And as well, we have seen that patients who have something called REM sleep behavior disorder, which is a sort of dream reenactment behavior, this can also precede some of the motor symptoms.

• 4:34Flora Lichtman?

  Dream reenactment behavior, like acting out your dreams while you're asleep?

• 4:38Speaker 04

  Yes, yes, this is something that is diagnosed based on a sleep study, but patients with Parkinson's, many will describe yelling out in their sleep, thrashing around, it's often noticed by their bed partners.

• 4:52Flora Lichtman?

  How early are these signs showing up?

• 4:56Speaker 04

  So this can happen many years, even decades, before motor symptoms can occur. And we know a large portion of people who have REM sleep behavior disorder, not everyone, but a large portion of them do go on to develop Parkinson's disease.

• 5:10Flora Lichtman?

  And smell too, the smell loss too, that early?

• 5:14Speaker 04

  Yes, smell loss as well. And so not everybody who has smell loss will have Parkinson's disease, right? We see, you know, there may be many other reasons to have smell loss. But we do see in patients who have Parkinson's disease, a large portion of them, before they develop motor symptoms, will have had a diminished sense of smell.

• 5:33Flora Lichtman?

  Michael, does the fact that it starts in the nose suggest that it is triggered by something we are breathing in?

• 5:41Speaker 03

  Yeah, so there are a number of theories on this. And it's not just the nose. So the nose would be one path to the potential start of Parkinson's. The other is the gut. And, and people talk about this as brain first, so coming through the nose, or gut first, actually coming through, you know, through the stomach and through your gut. And we find these abnormal protein clumps that you talked about in both places. And one of the real amazing and mysterious things about Parkinson's is when we look at the genetics of Parkinson's, about 13 to 15 people out of every 100 have a single piece of DNA

• 6:24Speaker 03

  that is abnormal or mutated. And that causes their Parkinson's. But the vast majority of people don't have that single mutation. And so we are now shifting a lot of our science, a lot of our effort, a lot of our research toward trying to understand what environmental factors and environmental influences might be impacting.

• 6:49Speaker 03

  Parkinson's, why it starts, why it spreads, why it progresses. And there are two areas that have really, you know, raised up in our, in our radar of what could be going on. One is, is air pollution and the other is pesticides and water. And, and so things that we take in from the environment seem to be related and have a high association for, for more cases of Parkinson's and other degenerative disorders that you mentioned as well.

• 7:26Flora Lichtman?

  Which, what specifically?

• 7:28Speaker 03

  We worry about pesticides. So things like Paraquat is, as one, you know, example of a pesticide that is highly associated with Parkinson's disease. When we think about water, we think about trichloroethylene. And also we think about dry cleaners as being one of the big offenders. And this is also a chemical that's used to degrease. It's a chemical that's used in the airline industry. It's a chemical used by factories, but when folks throw it away, it actually gets into the water supply and can actually vaporize and get up into the brains of folks with Parkinson disease. And so trichloroethylene is a chemical.

• 8:11Speaker 03

  And then in Alzheimer's disease, and in some cases of Parkinson's, it has a higher association with Alzheimer's is air pollution. And so we are beginning to shift our thinking to being more preventative as we see study after study showing us these associations.

• 8:31Flora Lichtman?

  I mean, does this suggest that we could be preventing Parkinson's if we had different regulation around certain chemicals?

• 8:40Speaker 03

  So I believe this is true. You know, as we begin to uncover these associations, we have to be careful, right? Because Parkinson's probably isn't one disease. Parkinson's is a whole body disease. There are probably a lot of different causes. And so the question comes up is, do we have, you know, needless cases? And can we spare this generation and the next? And I think the answer comes with the courage to follow the science and to do the experiment and to remove these things, especially when there are alternatives or ways that we can, we can live better.

• 9:26Flora Lichtman?

  We have to take a quick break. But when we come back, we're going to talk lots more about this, including about early warning signs. Don't go away.

• 9:40Speaker 01

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• 10:51Flora Lichtman?

  Okay, we're back. I'm talking with Dr. Emily Temmendonfar and Dr. Michael Okun about Parkinson's disease. Emily, tell me about this longitudinal study you mentioned, PPMI. What are you trying to learn?

• 11:03Speaker 04

  So, the goal of PPMI, it's really about early detection. Can we more accurately and more early detect Parkinson's disease? And also to speed development of new treatments. So, it's really twofold in that goal. You know, as we think about developing treatments to slow disease progression, with that, we need to also think about how do we diagnose earlier and more accurately?

• 11:38Flora Lichtman?

  Is there a blood test for Parkinson's? Like, are there biomarkers you can measure?

• 11:43Speaker 04

  We don't have a blood test for Parkinson's, but we do have other biomarkers. And so, that's been one of the challenges, is can we identify and validate biomarkers. Through this Parkinson's Progression Markers Initiative, we've been able to validate alpha synuclein seeding amplification assay, which is a spinal fluid biomarker. But it's hard to obtain spinal fluid. It's not the most comfortable process for people. So, we are still looking to identify other biomarkers that are more easily accessible, like in tear fluid, blood samples.

• 12:20Flora Lichtman?

  And how does the test work for participants?

• 12:22Speaker 04

  The participants in PPMI, they get a series of tests. So, they actually have a lot of tests when they come into the office. They not only have clinical assessments done, they also undergo imaging studies, including dopamine transport imaging studies.

• 12:41Speaker 04

  And our goal is also, I think, ultimately to identify biomarkers and have some quantitative data with that so we can better track disease progression and response to treatment.

• 12:53Flora Lichtman?

  How do you test smell loss?

• 12:55Speaker 04

  So there's actually a validated smell test where you can, participants can receive that in the mail and.

• 13:04Flora Lichtman?

  Like a card that, you know, like markers with a smell? What should I be envisioning?

• 13:08Speaker 04

  Exactly, exactly. So it's sort of like if you can envision those scratch and sniffs. So with those smell tests, they'll have different smells and they'll receive a score based on how well they did with each of the smells.

• 13:25Flora Lichtman?

  Emily, if I find that I do have smell loss, does that mean I'm at higher risk that I have Parkinson's?

• 13:33Speaker 04

  It doesn't mean you already have it, but you may have a feature, and this is part of what we're trying to understand. So not everybody with smell loss will go on to develop Parkinson's, but you may qualify to participate in the study in some form. But I wouldn't say, you know, if you have diminished sense of smell, that you should necessarily be very concerned you go on to have Parkinson's disease. It's something we're trying to understand better.

• 14:01Flora Lichtman?

  Michael, do we understand how the sort of protein misfolding spreads? You know, if it's starting in the nose or the gut, why does it keep going?

• 14:11Speaker 03

  Yeah, so, you know, we actually don't know the answer to that question. And one of the other very interesting, but also perplexing things for scientists is that everybody with Parkinson's disease doesn't have these abnormal synuclein, alpha, you know, misfolding within their brains. And we see differences in different types of genes, genetic forms of Parkinson's, and not everybody, it's not a one size fits all. And so we have begun to rethink this disease. And in fact, the idea that Parkinson's is just a disease of dopamine.

• 14:53Speaker 03

  We have now rethought that. We don't think Parkinson's disease is a disease just of the brain. We see it in the nerves outside the brain. We see it in the gut. We see it in the salivary glands. We see it in the skin. And so it's a whole body disease.

• 15:10Flora Lichtman?

  Hmm. Do we have any treatment that can slow the progression of the disease now? Emily?

• 15:16Speaker 04

  No, we don't have any treatment as it stands now that we know will slow progression of the disease. There are other interventions that we emphasize, including things like regular physical activity, diet, these sorts of things that we know can have a really positive benefit overall. But as it stands now, we don't have a treatment that we know slows disease progression.

• 15:46Flora Lichtman?

  This must be so frustrating for both of you who, you know, have devoted your lives to this. I mean, of course, it's devastating to patients, but it must also hit you hard.

• 15:57Speaker 04

  I'm very optimistic. I do think, you know, we were just talking about, you know, PPMI and the importance of these biomarkers. And it's really important, I think, in the context of building, you know, staging. One thing patients always come in and ask me is, what stage am I in? And that paradigm is sort of is shifting to this biological staging. And why that's really important is, as Dr. Oken was saying, putting into context all these different biomarkers. And some people may have certain positivity

• 16:38Speaker 04

  in some of their biomarkers and not in others. And putting that together to design clinical trials to develop more precise treatment plans for patients. This is really critical now.

• 16:50Flora Lichtman?

  Michael, what about you? Are you optimistic?

• 16:53Speaker 03

  I am optimistic. I, you know, so. As Emily said, we don't have the data yet as to what might slow disease progression. But we do know that certain things are really important. And, and study after study is showing that exercise, as Emily mentioned, is like a drug. It's now in major guidelines prescribed by every expert. So anybody who's listening should know that having an exercise regime, whether or not you can stand up, you know, or not, there are ways to exercise. Exercise is a very powerful drug. And there's data to suggest that it may, you know, have some effect in slowing the disease, although still debatable among scientists. Sleep is super important.

• 17:35Speaker 03

  And so I think we're entering an era of medicine where we can be more preventative. We can think about what we can do to, to prevent diseases, to try to stop them from developing. But even if you have a disease, the first thing you should do is remove some of these things from the environment and improve your situation. So if you have Parkinson's disease, get a carbon water filter, you know, make sure that you're, you have air purifiers around, particularly if you're in an urban area or an area without good air quality, and wash your fruit and get those pesticides off of them. There's no reason we shouldn't be doing those simple things.

• 18:11Flora Lichtman?

  Yeah, well, I would love to see society at large work on some of these problems because we are in a time where health optimization is sort of the name of the game, that it's now everyone's individual responsibility to keep themselves healthy. And I guess just to push back slightly on that, I would love to see this personally as a society-wide effort, you know?

• 18:36Speaker 03

  Hundred percent. And so, you know, we all want this to go faster. And I think the way to make it go faster is for each one of us. And every time that I go on the road for the Parkinson's Foundation, or talk about the book, or talk about Parkinson, I always tell the most important thing you can do is listen to people and ask people with Parkinson to tell their stories. The more we tell the stories of each other, we are a community, we are a village, the better chance we're going to have to decrease the amount of time that we can get to prevention and we can get to reducing the numbers and the burden of this disease. So tell your story would be a key message.

• 19:18Flora Lichtman?

  Emily and Michael, thank you so much for joining me today.

• 19:20Speaker 03

  Honored to be here.

• 19:22Flora Lichtman?

  Thank you so much. It was a pleasure. Dr. Emily Temmenden-Far is a neurologist specializing in movement disorders. She's a clinical assistant professor of neurology at the Keck School of Medicine of USC. And Dr. Michael Okun is a professor and executive director of the Norman Fixle Institute for Neurological Diseases at University of Florida Health. He's also the medical advisor for the Parkinson's Foundation. This episode was produced by Annette Heist. And if you like the podcast, please rate and review the show wherever you listen. I want to thank listener Reformed Luddite, who wrote, "This is the first thing I listen to each morning. I especially enjoy getting to hear from the scientists themselves." Me, too. Thank you for listening. See you next time. I'm Flora Lichtman.