NEW YORK – The Parkinson's Foundation recently expanded its PD GENEration genetic testing and counseling initiative to include more sites and greater outreach to traditionally underserved communities.
The patient advocacy and research organization expanded its study to 23 sites out of a target of 50, partnered with Morehouse School of Medicine to reach minority communities in the Atlanta area, and formed a Parkinson's Disease Gene Curation Expert Panel (GCEP) to help curate Parkinson's-related genes and their variants.
PD GENEration is a nationwide initiative to evaluate how offering genetic testing and counseling to people with Parkinson's affects their clinical care and enrollment in clinical trials. The study aims to eventually recruit 15,000 people, of which it has currently recruited some 23 percent.
Genetic counseling is a key component of the study, as Parkinson's remains incompletely understood, leading to significant concerns among those living with it regarding its potential course and the possibility of passing it on to future generations.
Despite this, genetic counseling is often not covered by public insurance plans, something that the Parkinson's Foundation hopes to eventually change.
"Ninety percent of our population is covered by Medicare," said James Beck, one of the study investigators and CSO of the Parkinson's Foundation. "Yet, Medicare won't consider genetic counselors as Medicare providers."
There are approximately two dozen genes currently linked to Parkinson's, although their exact contributions to the disorder's development and progression remain under debate. Even diagnosing Parkinson's requires assessing numerous signs and symptoms, as the disorder lacks a single definitive diagnostic measure.
"It's not like with diabetes," said Beck, "where you can just measure insulin levels."
Scientists conducting PD GENEration studies screen participants with a seven-gene next-generation sequencing panel, focusing on those genes most frequently associated with Parkinson's, according to available literature.
"There's such heterogeneity when it comes to Parkinson's gene panels," Beck said, noting that depending on the vendor, these can include anywhere from five to over 50 genes, sometimes including genes related to other neurodegenerative disorders such as Alzheimer's.
The Parkinson's Foundation's select gene panel, Beck said, "really narrows the focus and narrows the burden on both the clinicians and the patient."
For participants who test negative for this panel, Beck said that "screening the seven most common genes really allows us to reassure people that they're unlikely to have a genetic form of Parkinson's."
The diversity in Parkinson's gene panels, Beck explained, stems from a lack of official Parkinson's-related gene curation.
To that end and under the auspices of the National Institutes of Health-funded Clinical Genome Resource, the Parkinson's Foundation recently created GCEP, of which Beck is one of three chairs.
The approximately 50-person GCEP is tasked with developing a framework to determine whether a given mutation is causal to a particular disease. Panel findings will be entered into a publicly accessible database.
"If you're a drug company and you're looking to create a therapy for Parkinson's disease," Beck said, "that database is really critical because if the variants you're focused on are in that database, that's one less thing you have to talk to FDA about, to convince them that what you're doing is relevant to Parkinson's."
While the study focuses on a narrow gene panel, it seeks a wide scope for recruitment, particularly among populations traditionally underrepresented in clinical studies, such as African Americans and Latinos.
To that end, the foundation entered into a collaboration with Morehouse School of Medicine (MSM), a majority Black school in Atlanta, approximately six months ago.
Underserved communities tend to be socioeconomically disadvantaged and have less access to Parkinson's specialists and to medications and care services, resulting in delays in both diagnosis and treatment, as well as a lower quality of care.
They are also chronically underrepresented in studies, leading to significant knowledge gaps in the research and medical communities.
Studies have provided conflicting results, for instance, on the rates of Parkinson's disease among African Americans, with some showing roughly equal rates and others suggesting that this population sees significantly lower rates of Parkinson's. Finding that Parkinson's does affect African Americans — or other ethnic groups — less than others could shed light on how the disorder arises and therefore how to treat it.
"My hope is that we'll be able to see if there are any genetic variations or changes that we may not have been able to see in previous studies," said Chantale Branson, an assistant professor of medicine at MSM, who supervises the school's participation in PD GENEration.
These variations may also inform gene therapy developments, which could be hindered by a lack of diversity.
"If there's something down the line with regards to gene therapies, then everyone will benefit from it," Branson said.
Understanding how population genetics vary can also inform how patient support organizations might best allocate their resources.
"Genetic testing may also reveal specific populations to be more likely to be at risk of a Parkinson's diagnosis, which would allow organizations to focus on these specific community needs," said Andrew Price, social services manager for the Northwest Parkinson's Foundation, a separate entity from the Parkinson's Foundation.
While Morehouse is mainly helping recruit minority populations into PD GENEration, the researchers involved will also be able to access the study's data to perform their own analyses.
Individual participants in PD GENEration will also have access to their own genetic test results, in contrast with many genetic studies. This, says Beck, is important in building trust, educating patients, and generally retuning value to participants.
"A lot of research studies," he said, "just ask stuff of people — time, a lot of blood, a lot of other things — and never give anything back. This is part of empowering people with Parkinson's and is where we need to go when it comes to clinical research moving forward."
Participants also have the option to undergo in-person or at-home testing, with all samples sent to Fulgent Genetics, a CLIA-certified and CAP-accredited lab in Los Angeles.
The PD GENEration study has already led researchers to some families and individuals with Parkinson's who have very rare mutations. Although the study tests for seven genes, participants who test negative but have family histories of the disorder may undergo further testing.
The study has uncovered one person, for instance, who has a sibling with Parkinson's and a very rare mutation of interest in a gene called CPS35, which Beck hopes to better characterize clinically.
As the study continues to move forward, Beck also plans for it to expand beyond the US.
"The Parkinson's Foundation is international," Beck said. "We have centers of excellence in Canada and throughout the world, so we're looking to partner with some centers of excellence [abroad] in order to be able to bring this testing to a wider range of individuals."