The chief scientific officer of the Parkinson’s Foundation discussed how the PD GENEration initiative tackles 1 of the greatest unmet needs for patients with Parkinson disease.
The Parkinson’s Foundation and Sanofi recently announced funding for a collaborative research effort that will advance the availability of genetic testing and counseling for people with Parkinson disease (PD). Named PD GENEration: Mapping the Future of Parkinson’s Disease, the initiative includes a first-of-its-kind national study that will contribute to the biological understanding of the disease and help researcher assess the impact of genetic mutations within PD.
There is an estimated enrollment of 15,000 people with PD, who will undergo a 4-step process: Attending an appointment at a Center of Excellence or Parkinson Study Group site, developing the results, meeting with a health care professional, and filling out a post-process survey. In addition to uncovering more on the pathology of genetic PD, the initiative will help facilitate future clinical trials for patients with genetic PD. Instead of testing patients after they’ve been enrolled in clinical trials, this important clinical history will already be available.
As part of our NeuroVoices series, James Beck, PhD, chief scientific officer, Parkinson’s Foundation, discussed the initiative’s entirety with NeurologyLive, including the barriers that prevent more widespread testing, gaps in knowledge of genetic PD, and the advantages genetic testing brings to the clinical trial setting.
James Beck, PhD: PD GENEration: Mapping the Future of Parkinson’s Disease initiative is designed to provided free genetic testing and counseling to 15,000 people with Parkinson disease all within the clinical setting. We think it’s important to provide accurate information to people with PD to know whether they have a potential genetic form so they can get that counseling, which is so critical but hasn’t been offered mandatorily to date. We also want to include the condition because we’re seeing a potential sea change in the realm of future therapies for Parkinson disease. We’re moving to an era of precision medicine for PD. These experimental therapies go to clinical trials and we want people with PD to participate, but they need to know if they have a genetic form of PD first. It’s very important to include the clinician as part of that process because it requires that physician-patient partnership to make that decision to go into clinical trials. Ultimately, what it comes down to is a person with PD will ask their doctor, “Is it okay to participate in this trial?” We hope that by including both partners in that discussion ahead of time, they’ll already be able to move quickly to say yes or no.
To date, people with Parkinson disease have no had access to widespread genetic testing. There are a lot of barriers to get genetic testing for people with PD. Primarily because, up until this point, we’re right at the time of a sea change where precision medicine therapies, hopefully, will be available for patients with PD. But before then, understanding whether you have a genetic form of PD was not significant and did not impact your care. It was good to know information but there was no action associated with it. Third party payers and insurance companies weren’t quick to reimburse for genetic testing for PD because it didn’t influence treatment outcomes.
Now, we think that’s going to change. We’re doing our part to get the community ready because those barriers are still there. It’s still very difficult for a person with PD to go out and get genetic testing on their own. In fact, the genetic testing that we offer as part of PD GENEration is next to impossible to get by an individual. There’s no place that can offer this type of comprehensive genetic testing. They would have to go to 2 or 3 different providers in order to essentially get the same information we’re able to provide by combining it together in PD GENEration.
Our pilot study was conducted at 6 different sites throughout the US. We were looking to understand a few things. First, is it even feasible to do what we want to do? 15,000 people is a lot of individuals. We really needed to understand the ability in order to do this at scale. We also wanted to understand what people did or did not know in regard to genetic testing and PD. Those analysis are going to be forthcoming a little bit. Right before the COVID-19 pandemic, we recruited about 300 individuals into our study. The scientific consensus for how many people have a genetic form of PD is about 10%, which is remarkably low. What we found was about 17% of our participants had genetic forms of the disease, some incredible rare as well. We believe is that we’re going to find more than what most scientists believe. It may not be 17% once we reach 15,000, but we certainly believe it’s going to be higher than 10%. In our PD GENEration study, we’re looking at the full length of 7 genes associated with PD. There are a dozen or more genes associated with PD, but they get vanishingly rare as you go down the column. We look at those genes in their entirety and report back to people with PD and tell them if they have a mutation relevant to their disease.
The unmet needs in the knowledge gaps are everywhere. As part of our study, we conducted a study of neurologists who are very familiar with PD. This is part of a group called the Parkinson Study Group, which is made up of academic neurologists who have real interest in clinical trials. We asked them basic questions about genetics and PD. What was really telling was that despite the tremendous skill these doctors have, they weren’t comfortable talking about the genetics of PD. One might say this is the crème de la crème of neurologists focusing on PD. That was a real warning for us as a community, and an increased need to educate clinicians about PD and genetics as well. We’re working to undertake those efforts to be able to educate clinicians.
The second thing we realized, too, is that people with PD don’t know much about genetic forms either. A frequently asked question is: how many people have genetic forms of PD? As I mentioned, genetic forms of PD are relatively rare, about 10%, while we saw 17%. But it is certainly less than 20% of individuals. That said, just because this is a rare event doesn’t mean it’s not worth investigating or studying. Our hope is that precision medicine and therapies which may come to bear for genetic forms of PD may be used more broadly.
I’d like to talk about the example of statins. Statins are used broadly for people who have high cholesterol or at risk for cardiovascular disease. What led to the development of statins was the understanding of an incredibly rare form of genetically high cholesterol called familial hypercholesterolemia. Understanding how that gene was mutated and what led to the excess production of cholesterol ended up leading to the development of statins, which interrupted that pathway. Not only did it help people with genetic forms of high cholesterol, but it helped people out more broadly.
We think, and I hope, that individuals who have genetic forms of PD will be able to pave the way with new therapies which can then help the broad community. There’s evidence to suggest that genes that have gone awry in patients with genetic forms of PD, may have gone awry in individuals who don’t have genetic forms. For example, the 2 targets right now for clinical trials are 2 enzymes that are made by 2 different genes. Each has a series of mutations which can lead to those enzymes not working properly. Individuals with PD who don’t have genetic forms of PD may have those enzymes be overreactive or not working properly, which could occur in people with genetic forms of PD. It’s complicated, but the idea is individuals with idiopathic PD may be able to benefit from the hard work and effort of individuals with genetic PD who are willing to participate in clinical trials in order to advance our field forward.
They’re tremendously important. We don’t walk around with a red letter on our chest saying we have a genetic mutation, and that’s certainly not the case with PD. There’s a million people with PD in the US, the vast majority of which do not know they have a genetic form of PD. Even if they did direct consumer testing for PD, those were very targeted, which is not very useful for the broad majority of individuals with PD.
That’s why we created PD GENEration. We want to be able to fully test 7 genes related to PD that we believe are going to be on the cusp of precision medicine. That is where pharmaceutical companies are looking to create therapies to potentially slow or stop those individuals who have those mutations. Knowing whether you have a genetic form of PD is crucial if they want to participate in a clinical trial. On an operational level, how do you do that on a practical level? One way is that you can enroll everybody with PD and then start testing them. If they have that mutation, then they can proceed in the clinical trial. That is unfortunately very inefficient. What’s more efficient is to be able to offer widespread genetic testing now. As soon as these clinical trials become available to individuals, they already have that answer. They can proactively enroll in that trial and be able to speed the process by which these drugs are developed, tested, and hopefully approved.
I would encourage people who are interested in understanding whether their form of PD is genetic to go to our website. There’s an opportunity for them to sign up to participate in the trials. We’ll be honest—there’s a lot of demand right now. But we’re working to expand our capacity. Our goal is to be able to reach out to 15,000 people with PD to offer the free genetic testing, counseling, and ensure that their clinician is part of this process. They can then use that information to learn more about their disease, while also using that information to help other people with PD by hopefully enrolling in clinical trials.
Transcript edited for clarity.