Dan Keller 0:08
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. Parkinson's disease may not be just one disease, but may be the end result of processes governed by several genes. PD may take different forms, with patients experiencing different symptoms and courses of progression. So the Parkinson's Foundation has initiated PD GENEration: Mapping the Future of Parkinson's Disease, the largest genetic study ever undertaken in PD in the United States. It will recruit 15,000 participants who will receive genetic testing as it relates to PD, along with genetic counseling. They will be kept fully informed, quickly getting their test results back, which may empower them to decide to participate in clinical trials of potential treatments, as well as to make decisions about their lives. Currently, the foundation has launched a pilot study at selected sites across the US and will expand nationwide next year. This episode marks the second in our PD GENEration podcast series, in which we'll be providing you with quarterly initiative updates. Today's update marks the first participant enrolled in the study. To learn more about both the advocate and investigator perspectives, I spoke with patient advocate Anne Hall and neurologist and principal investigator of the initiative, Roy Alcalay, to get some background on PD GENEration.
Roy Alcalay 2:15
PD GENEration, the Parkinson’s Foundation genetic initiative, is an initiative to offer genetic testing and counseling for people with Parkinson's so they can be counseled about their genetic makeup and get the results back to see whether they carry one of the genetic risk factors for Parkinson's that may affect their care or ability to participate in clinical trials.
Dan Keller 2:40
Does it have broader use in terms of discovering things about Parkinson's disease and how genes contribute to it?
Roy Alcalay 2:49
So I think that the field of genetics and Parkinson's evolved tremendously in the last 20 years, since the first discovery of a gene linked to Parkinson's. I think the innovation and the importance of PD GENEration is that it brings it from the researchers and from the scientific publications to the people with Parkinson's. So it's not just that the genes appear on publications. Now you can know, if you're interested, if you're a carrier of one of these genes. Now, I think that once people with Parkinson's are more aware to whether they carry mutations or not, this will change the entire perspective of the research around these genes. For example, if some more people that have those genes are identified, we can understand a little bit better how their Parkinson's looks like.
Dan Keller 3:39
How much do genes contribute to Parkinson's?
Roy Alcalay 3:42
Genes contribute significantly to Parkinson's. People try to put a percent to it, but I think it's a little bit difficult to do that. We anticipate that among participants in PD GENEration, roughly 10% will find a gene that is linked to Parkinson's in them. These 10% would carry a gene. But it's not that all those who carry the gene have Parkinson's disease. So this is a risk factor—in some cases, an important risk factor—but a risk factor. So even though that may have contributed to them having Parkinson's, there are other causes, other risk factors that need to be discovered.
Dan Keller 4:21
I understand PD GENEration is going to be done in two phases. Can you tell me about those?
Anne Hall 4:26
The first phase will be what we're calling a pilot study. It will involve six of the Centers of Excellence: the University of California, San Diego; Columbia University Medical Center in New York; Massachusetts General; Northwestern University; the Struthers Medical Center in Minnesota; and the University of Pennsylvania. It'll collect data from 600 patients, 100 from each of the centers. And in the second phase, we'll collect data from 15,000 individuals with Parkinson's. So it'll be a really big nationwide study as it rolls out in the second phase.
Dan Keller 5:00
What do you hope to gain from the study?
Roy Alcalay 5:03
One of the major roles of the PD GENEration study is to give people with Parkinson's their genetic results back and see how that affects their treatment and how that affects motivation of people to participate in clinical trials that involve these genes. Many clinical trials for drugs that may slow down or prevent Parkinson's have failed, and researchers are trying to figure out why. One of the potential reasons is that we treat Parkinson's as one condition, while Parkinson's may have multiple causes. So it's time to think a little bit more about precision medicine in Parkinson's. It completely revolutionized the way breast cancer is treated, the way other cancers are treated. And the question is, whether drugs are developed that work on a specific gene or biological pathway, will that be the way to slow down or prevent Parkinson's? And then the next question would be, who would benefit from such treatment? Only those with mutations, or maybe a larger, broader Parkinson's population?
Dan Keller 6:03
Once someone joins the study and gets tested, how long will it take for them to get their results back?
Roy Alcalay 6:10
So our goal is six weeks. We anticipate the lab and the processing to take roughly three to four weeks, and then to schedule the follow-up appointment with a doctor or with a genetic counselor, we would give that two weeks. So within six weeks from enrollment, we expect the participants to receive their genetic results back.
Dan Keller 6:29
Anne, why participate? What is someone going to get out of this, and what can they do for the broader Parkinson's community?
Anne Hall 6:36
Dan, one of the things I was thinking about when I was first asked to join the steering committee to talk about PD GENEration was "Why now?" When I was first diagnosed about 10 years ago, if someone had asked me to do genetic testing, I think I probably would have said no, because I didn't see what the point would be. There really wasn't anything that could be done with that information. At that time, things have really changed a lot, though, in the research field for Parkinson's, and also in sort of people's attitudes about genetic testing in general. So why this is important, and why now, is because there's a strong interest that people with Parkinson's have to find out what their genetic background actually is. And the one really important thing about this study is that it's not only nationwide in its second phase, but also it's going to be free, and it's a very comprehensive look at the genetic background of people with Parkinson's. So it's going to be quite different than some of the other more commercially available genetic tests. Also, there are multiple drug tests in clinical trials right now that look at particular genetic backgrounds, and there's going to be more of that as we go forward. So individuals who know that they have a genetic marker or know that they don't will then be able to more selectively participate in those clinical trials, and that can only advance the field of genetic study for Parkinson's and the development of better treatments going forward.
Roy Alcalay 8:00
I am very hopeful that treatments that target genetic pathways will modify Parkinson's and will change the way we treat Parkinson's. And there is a little bit of a question of "the chicken and the egg," because you would say people should know their genotype if that will make them take different drugs. But how would we know if those drugs work if people don't know their genotype, participate in clinical trials, and advance the field forward? So I think this is a great opportunity for people who are interested in getting their genetic results back, to get it with genetic counseling, without cost, and then decide whether they want to participate in those clinical trials. It is true that it's not for everyone.
Dan Keller 8:42
The drugs you refer to, are these current drugs, or are you envisioning drugs that specifically target pathways governed by those genes?
Roy Alcalay 8:52
So there's no FDA-approved drugs that work on these genes, but there are different drugs that are being tested in different stages of clinical trials—Phase I, Phase II clinical trials—that recruit only people with a selected genetic mutation or gene variants into the studies. There's at least five studies like that worldwide, so it's not just one study that will either happen or fail. I'm very hopeful that the more studies that take place, that at least one of them, if not more, will come through and hopefully revolutionize treatment for Parkinson's.
Dan Keller 9:27
These sound like fairly long studies if you're looking at progression. Is that true?
Roy Alcalay 9:32
Just like any other studies for Parkinson's that are disease-modifying trials, they will take more than a year; it's like a year or two years, because Parkinson's is relatively slowly progressive. So if you want to see that you change the progression, you need to follow up people a little bit longer.
Dan Keller 9:49
Is there also a component of genetic counseling in this?
Anne Hall 9:52
Absolutely, yes. One of the things that we're going to be looking at in the study is whether there's a difference between how the results are conveyed—in other words, whether there is more satisfaction with results conveyed through a telemedicine approach by video link or telephone, or by the clinicians at the facility that participants participate in.
Dan Keller 10:16
And are there genetic counselors at those facilities?
Anne Hall 10:19
Most have genetic counselors. We're still working out some of the details on exactly how that will be delivered.
Roy Alcalay 10:26
But one of the major questions is whether physicians who treat people with Parkinson's would be comfortable, and can they do an excellent job returning the genetic results back? I think that it is very likely that in a few years, just like people with newly diagnosed Parkinson's disease get a dopamine scan, a DaTscan, they may get genetic testing as part of the workup of their Parkinson's disease, and then, usually, that should be done by the clinicians and not referred for additional counseling with genetic counselors. So I think that in the long run, the Parkinson's Foundation has a mission to educate physicians about genetic counseling, about the data, about those genes, so people who treat people with Parkinson's can counsel as appropriately as possible.
Dan Keller 11:12
What's important to add or that we missed?
Roy Alcalay 11:15
There is a major empowerment component to this grant. I have participated in genetic studies in Parkinson's since 2007, and I have always been frustrated that because of IRB issues and because of the quality of the way we collected data in the genetic lab, that it couldn't just streamline the results back to participants. And I also learned a lot from participants—that people wanted to know their genetic makeup even when there wasn't something to act on it, and people went to direct-to-consumer testing or tried to get the results in other ways. Here, we're giving people the opportunity to get the results back from an excellent lab with genetic counseling if one wants to know their genetic makeup. I think that is the right way to doing it.
Anne Hall 12:00
I just want to piggyback on what Roy said about that as well, that one of the important things about this is, since it is such a comprehensive result that you're getting back, you're not just going to find out that you may or may not have a marker on one or two of the most common Parkinson's genes. You'll get a much broader picture of your health profile genetically, and that can really influence how people make decisions going forward—whether they want to have an end-of-life plan, which could include sort of like a bucket list; whether they want to talk about leaving their jobs early if they're a younger onset individual. So some of these things are really important decisions that people can't always make if they don't have full information. And that will also include the many people we believe who will participate in the study who may not find out that they have any markers that we know of at this time, but they could in the future find out, since the information will be maintained by our partners in this initiative. And if something comes up in the future with regard to additional markers, they will have the opportunity to participate in further studies about that as well.
Roy Alcalay 13:01
And also think we need to think about it in the broader picture of other neurological conditions—that people are very frustrated. How come there's still no treatment for Alzheimer's and ALS and Parkinson's disease? And I think that one of the problems and one of the things that held us back in all these conditions is really treating all patients as a group, rather than looking at subgroups within the people with Parkinson's. Now, anyone who knows people with Parkinson's knows that it's not one condition, and not one Parkinson's looks like the other. So this is an opportunity for us to understand better what's causing it and to see whether we can help clinical trials that intervene on these pathways.
Dan Keller 13:43
Very good. Thank you both. To learn more about PD GENEration, you can visit our website at parkinson.org/PDGENE. You can find out about why it is being conducted, how PD GENEration works, find a site near you, and learn about how you can get involved. You can also visit the PD GENEration Frequently Asked Questions page at parkinson.org/PDGENEration/FAQs. You might also want to go back and listen to the first episode in the PD GENEration series, Episode 61, featuring Dr. Jim Beck as he talks about the role of genetics in PD. Episode Seven is also relevant and points out how knowledge of genes involved in PD may help lead to better treatments, even slowing down progression. Of course, our PD Information Specialists are available to answer questions and provide information in English or Spanish about this topic or anything else having to do with Parkinson's. You can reach them at 1-800-4PD-INFO. For questions about the topics discussed today, or if you 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. Thank you for listening.
