Around 15% of Parkinson’s cases are thought to involve a significant genetic component — but genetic testing for the disease has not been common.
“Mutations in several different genes increase the risk of Parkinson’s disease,” Roy N. Alcalay, MD, MS, a neurology professor at Columbia University and principle investigator of PDGENEration, said in a press release. “Until recently, we rarely offered genetic testing for people with Parkinson’s because the benefit had been unclear.”
That paradigm is changing, though. Thanks to recent research, an individual’s genetics can sometimes be used to predict disease outcomes, and new medications that are designed for people with specific Parkinson’s-associated mutations are starting to enter clinical trials.
“From our own genetic studies, I realized many people were eligible to enroll in such trials, but they didn’t know it because nobody told them about their genetic status,” Alcalay said. “I wanted to find a simple, ethical way to offer Parkinson’s patients information about their genotype if they are interested.”
That led to PDGENEration, which aims to give free genetic testing and counseling to people with Parkinson’s. The program currently is only available at Columbia, but there are plans to expand it to other centers in the U.S., with a goal of enrolling 15,000 patients. There are no age restrictions to participation.
PDGENEration will test patients for seven genes that are known to be related to Parkinson’s: GBA (glucocerebrosidase beta), LRRK2 (dardarin), PRKN (Parkin), PINK1 (PTEN induced putative kinase 1), PARK7 (DJ-1), VPS-35, and SNCA (alpha-synuclein).
As an illustration of the possible utility of this test, take GBA, which is mutated in up to 10% of people with Parkinson’s. The enzyme that this gene codes for helps cells clear out gunk, so when the gene doesn’t work, toxins can accumulate in cells. That is thought to be the mechanistic link to Parkinson’s. Clinical trials specific for Parkinson’s patients with GBA mutations are already enrolling (e.g. NCT02906020).
In addition to giving some patients information about clinical trials for which they might be eligible, PDGENEration hopes to gather data that will help researchers and clinicians to better understand the genetics of the disease. This will go beyond the seven known genes and include sequencing of all of the parts of the genome that code for protein (whole-exome sequencing).
“These data may be used for future discovery of additional Parkinson’s-related genes,” said Alcalay, adding, “We will invite all those who completed the genetic study to enroll in a longitudinal follow-up study, which could help us better understand how these mutations affect Parkinson’s progression. For instance, can patients with these genetic risk factors modify their risk with lifestyle changes?”
The genetic testing results obtained through this study will be confidentially sent to a secure central database for future Parkinson’s-related research.
More information about the program and how to enroll can be found here.