Dan Keller 0:00
Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow.
With rapid and powerful advances in genetic analysis over the past couple of decades, researchers have been able to pinpoint specific variants in genes that are associated with particular forms of diseases. There are now more than 20 genes that are associated with Parkinson's disease, and different variants of these genes may be relevant to different forms of the disease, its progression, and potentially its treatment. The Parkinson's Foundation study, PD GENEration: Mapping the Future of Parkinson's Disease, aims to explain how these genes influence the susceptibility to PD and the course of the disease. This is the fifth episode in our PD gene podcast series, in which we'll be providing you with quarterly initiative updates.
This episode marks the halfway point for the PD GENEration study. We're excited to share that enrollment has reached nearly 300 participants within five months of the study's launch. The average age of participants is 64 years old; the youngest participant is 30 years old, and the oldest is 88. While the pilot study was launched at six sites across the US, there has been an overwhelmingly positive response from the PD community, with PD GENEration participants represented across 21 states. Over 38 participants, about 13% of the cohort, have been identified with a genetic form of Parkinson's disease. In contrast, most published studies report the prevalence of genetic carriers to range from 5% to 10% of the total population of people with Parkinson's.
PD GENEration's early success represents the collective efforts of the Parkinson's community. When I spoke with Dr. Tanya Simuni and Dr. Michael Schwarzschild, they explained how genetic studies can define discrete subsets of people with PD, leading to clinical trials more targeted to different causes or forms of the disease. Today's podcast is sponsored by Kyowa Kirin. I guess the main question is, why are genetics in the spotlight now as it pertains to Parkinson's disease?
Dr. Tanya Simuni 3:13
That is a very good question, as you well know. The biggest, ambitious goal is to find, if not a cure for Parkinson's disease, ways to effectively slow progression of the disease. And despite multiple trials over at least 30 years, we have not been successful so far. And while there are a number of reasons for failure to achieve that goal, one of them is looking at Parkinson's as one single disease. And we clearly recognize that under the umbrella of Parkinson's disease, there are different forms, and one of them—and of great interest—are the subsets of patients who carry genetic mutations.
While the number of people with a single mutation responsible for the disease is very small—it is approximately 5% to 10%—the mechanism of the disease relevant to those people can also very well be relevant to the Parkinson's community at large. And that's the reason a combination of an exponential increase in the knowledge of genetics combined with the development of new therapeutics targeting specific genetic mutations has put genetics in the spotlight of research in Parkinson's.
Dr. Michael Schwarzschild 4:38
Now that we are targeting the genes that contribute at least to a subset of Parkinson's patients' disease, we now know that we're really on terra firma in terms of the relevance of the targets. We know that if we are successful in targeting those genetic contributions, we are targeting what's causing the pathology of the disease, and that's really a quantum advance compared to the previous targets that we've had. So for multiple reasons, but particularly because of the causality of genetic forms of Parkinson's, there's a step forward in terms of the rationale behind our enthusiasm.
Dan Keller 5:14
Which genes are of particular interest?
Dr. Michael Schwarzschild 5:17
So the two that have risen to the top of at least 20 different genes that have been implicated in Parkinson's disease are one that's called LRRK2 and another one that's abbreviated GBA.
Dan Keller 5:29
The Parkinson's Foundation has a big initiative now called PD GENEration, and it will be looking at some genes, among which are LRRK2 and GBA. What is the benefit to a patient personally in participating in any of these?
Dr. Tanya Simuni 5:46
Very good question. I believe that I can speak for the whole of the community of people living with Parkinson's that they are looking for better therapies and, ultimately, the cures. And genetically targeted therapeutics provide the new era in the therapeutic development in Parkinson's. So I think that unequivocally, the benefit and responsibility is to participate in the studies, because we can design the best study, but if the study does not recruit participants, we will never have the answers.
Dr. Michael Schwarzschild 6:25
And if I could add to Dr. Simuni's point, maybe even more broadly, participating in clinical trials is very, I believe, empowering for people with Parkinson's disease. Whether in participating one is randomized to the placebo group or the active intervention, it's only through these clinical trials that we're going to get to the answers that everybody wants. And being able to participate and fight the disease that way, I think, is one of the most common gratifications for people who participate.
I would add also, at the level of these LRRK2 and GBA targeted genetic forms of Parkinson's trials, that there's sort of another layer of value and benefit that can be provided with a general trial. There's a chance, of course, that the therapeutic will work, and that you'll be in the active group, and you'll benefit directly. But the knowledge, as I just mentioned, will invariably be helpful to the whole Parkinson's community and generations to come, so it serves all people with Parkinson's.
In the case of genetic forms of Parkinson's, in between oneself and all people with Parkinson's are one's family and one's offspring and future generations who will carry at least some small risk because of the volunteers for these studies being able to qualify because they have an altered form of a gene that will be inherited by members of their family. And so I think there's one other additional motivation that, regardless of the result of the study, their families stand to benefit substantially as well.
Dan Keller 7:53
Unlike a drug trial where you're randomized and you might or might not get the drug, but you might or might not get the side effects and negative outcomes, it seems like it's mainly benefit. You're contributing to the knowledge, and since there's no intervention—they're not giving you anything—there's no potential harm. I would think maybe there's some anxiety, but it seems like the balance falls on the upside.
Dr. Tanya Simuni 8:18
So, Dan, you're now speaking about observational studies that would recruit participants to identify whether they're carriers of a particular genetic mutation, and to see whether their clinical course of the disease and underlying biological samples, whatever collected in the study, are different from the people who do not carry the genetic mutation. So there, you are absolutely right: the harm is minimum, the knowledge gained for the scientific community is tremendous, and as Dr. Schwarzschild indicated, knowledge gained not only for the scientific community but for the participant empowering themselves that they're contributing to that knowledge.
Dr. Michael Schwarzschild 9:01
And just to clarify, Dan, too, in terms of LRRK2 and GBA clinical studies versus trials—because semantics can be particularly tricky. We've highlighted the few early-stage trials, which are intervention studies and do, of course, carry risks and benefits depending on what one's randomized to. There's a whole raft of preceding and ongoing observational studies, like the Fox Foundation's PPMI study and other cohorts, which are enriched for genetic forms of disease that have actually helped lay the groundwork for these trials. And yes, in those studies, there's a lot to be offered with lower risk and lower benefit for the individual.
Dan Keller 9:40
Yeah, I was particularly thinking of the PD GENEration initiative that the Parkinson's Foundation is starting, which is purely observational.
Dr. Michael Schwarzschild 9:48
Right. And then, so in our vernacular, we consider the PD GENEration an observational study as opposed to a trial, but it's tricky.
Dan Keller 9:57
PD GENEration is going to be gathering a lot of data over several years. I wonder when it's going to really have enough volume or mass to be really informative.
Dr. Michael Schwarzschild 10:11
The whole purpose of PD GENEration, until there are therapeutics for this, is to feed these exact trials that we're talking about. So it's definitely interrelated.
Dan Keller 10:18
You agree, Dr. Simuni, that observational studies like PD GENEration can feed into intervention trials?
Dr. Tanya Simuni 10:26
Absolutely. Observational studies serve a number of purposes, depending on the objective of the study: collecting information of the clinical profile of the participants, of underlying biological characteristics of the participants, and undoubtedly no less important—and probably mostly important—identifying the participants for the future ongoing studies. And it is specifically relevant when we are targeting genetically positive individuals. We already talked about the fact that out of the whole Parkinson's community, it's less than 10% that would carry those genes. So we need that identified population who know their genetic status to be informed of the studies that test therapeutics for that particular gene.
Dan Keller 11:14
If it's, say, 10% of the population with Parkinson's who carry those genes, are there other things we should also be looking at—not only genetics, but other kinds of biomarkers which would define subpopulations?
Dr. Tanya Simuni 11:28
This is a million-dollar question with a million-dollar answer that we've been trying to come up with. Yes, absolutely, we should. And we're hoping that a small subset of genetically positive population will teach us more about what we call sporadic population. But yes, identifying the underlying biology that defines the course of the disease in that non-genetic population, looking at the other variables, absolutely will inform the design of the future studies.
Dan Keller 12:05
Anything important to add that we've missed?
Dr. Tanya Simuni 12:09
I think that both of us would like to close saying that the scientific community is working very hard to bring next-generation studies, more informative, with a smarter design of the studies, with better molecules. But as the scientific community is advancing, it is equally the responsibility of people living with Parkinson's disease to be active contributors and participants. And obviously, participation in the studies is essential to provide us answers.
Dan Keller 12:40
Do you find people are eager to get into clinical trials?
Dr. Tanya Simuni 12:45
We are advancing, and I believe that in order for people to participate in the studies, a number of things have to happen. They need to be informed of the reasons for the studies, they need to be informed of the ongoing studies. Because movement disorders physicians take care of the minority of people living with Parkinson's disease, so it is on us, the responsibility, to educate the patient community, to educate the community of neurologists and other physicians taking care of these patients so that the information is out there. I believe that people want to participate, but they need to have the information where, how, and whether they qualify.
Dr. Michael Schwarzschild 13:29
And I'll just compliment Dr. Simuni's point to highlight the flip side of that improvement that I think we've seen as clinicians over decades of clinical trials for Parkinson's disease—that enrollment, always a challenge, is increased as patient participants understand why the disease, how it's being targeted, and what role they have to play. At the same time, I think the research community has also improved in understanding the partnership between the patient community and the Parkinson's Foundation, which has actually highlighted this nicely with their Patient Advocacy in Research program, their PAIR program, which partners increasingly with clinical trials like Dr. Simuni and I oversee, in which we are informed by the patient perspective with direct representation of people with Parkinson's serving on our steering committees and the like. So it's really at every level that we're improving this enterprise. It's a partnership with the patient community through podcasts like this, understanding what the challenge is and how they can contribute, and all of us coming together with improving ideas like the genetic trials in Parkinson's represent that make it so hopeful.
Dan Keller 14:39
Very good. Thank you both.
Dan Keller 14:50
The only way that science advances and treatments and cures can be found is by people with a disease participating in medical studies. For information on the PD GENEration initiative and how to participate, go to parkinson.org/pdgeneration. Even more information can be found by searching our website for PD GENEration, as well as listening to episodes 7, 14, 15, 64, 67, and 73 of this podcast series.
Don't forget that April is Parkinson's Awareness Month, and you can help people with Parkinson's in your community by getting involved. This year's theme is #PlanForPD, highlighting the importance of creating a plan for best managing Parkinson's. Learn more at parkinson.org/awareness.
In May, our signature spring walks, Moving Day, a Walk for Parkinson's, are going virtual. Even though we won't be able to move together in person, we can still unite in the fight against Parkinson's from the comfort of our homes. Join us online Saturday, May 9, for a virtual walk to celebrate the power of exercise by moving and fundraising to beat Parkinson's together. Learn more and register at movingdaywalk.org.
As always, our PD Information Specialists can answer questions and provide information in English or Spanish about today's topics or anything else having to do with Parkinson's. You can reach them at 1-800-4PD-INFO. To receive news and updates about future events and resources, you can opt into our email list at the bottom of our website's homepage. If you have questions or want to leave feedback on this podcast or any other subject, you can do it at parkinson.org/feedback.
If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts, or wherever you get your podcasts. At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life today. To that end, we'll be bringing you a new episode in this podcast series every other week. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO, that's 1-800-473-4636. And thanks again to Kyowa Kirin for sponsoring today's podcast. Thank you for listening.
