NEW YORK (GenomeWeb) – The Parkinson's Foundation (PF) said last week that it will begin a country-wide program called the Genetic Initiative in order to offer free genetic testing to individuals with Parkinson's disease, as well as family members who have a potential genetic risk for the condition.
By collecting the patients' genetic information in a larger database, the foundation hopes to connect families with genetic counseling and clinical trials, as well as further understand the genetics that may cause Parkinson's.
Starting in 2019, the Miami-based non-profit will phase in the initiative in a number of its Centers of Excellence across the US. The foundation currently has a network of 28 such centers that partner with local hospitals and clinics.
Through a clinical study started in 2009 called the Parkinson's Outcome Project (POP), these partners have collected information on over 10,000 patients. Under the new Genetic Initiative, select centers will recruit individuals diagnosed with Parkinson's or whose family has a genetic history of the disease to test for mutations in LRRK2 and GBA, as well as offer genetic counseling. The foundation will include the data collected from the Genetic Initiative as part of the POP's genetic repository in order to develop new research avenues and treatment options for patients.
"We announced this initiative so that we have a group of people around the table to ensure we have something that is useful to everyone in the PD community," Parkinson's Foundation CSO James Beck explained. "People need to find out their genetic status in order to participate in these clinical trials, and no one knows that information for the most part."
Parkinson's disease is a movement disorder caused when the dopamine-producing neurons in a section of the brain begin to deteriorate. While one of the most common neurological disorders, PD's risk factors are mostly unknown. However, researchers believe that the disease may be caused by a complex interaction of genetic and environmental factors. Because there is no diagnostic test for Parkinson's disease, doctors must rely on a combination of clinical exams and tests evaluating symptoms.
In its mono-genetic form, Parkinson's disease is thought to be caused by mutations in a person's LRRK2 or GBA gene. According to Beck, only a small amount of people with Parkinson's actually have a mono-genetic form of the disease, as the mutation appears in 10 to 15 percent of the patient population.
LRRK2-related Parkinson's is a mild form of the disease that uses less cognitive involvement and develops at a slower pace. A number of mutations in the gene can cause Parkinson's disease, including the common T2-29S mutation. A patient, however, requires at least two autosomal dominant copies of the mutation in the gene to develop LRRK2-related Parkinson's.
According to Beck, genetic mutations or variants in GBA, on average, lead to a slightly more aggressive course of Parkinson's disease. GBA-related Parkinson's demands more cognitive involvement and leads to a faster rate of progression of dementia in patients. In contrast to LRRK2, an individual's DNA only requires a single copy of the GBA mutation, as the risk factor for Parkinson's disease increases eightfold or more, Beck said
Parkinson's Foundation scientific advisor Roy Alcalay explained that while detecting LRRK2 mutations requires a relatively straightforward PCR-based test, the mutation only occurs in about 1 percent of the patient population. In contrast, GBA-related Parkinson's is difficult to detect because several recombinations of the gene have been shown to be pathogenic, and because of the existence of a pseudogene that can mimic GBA.
"Because not all of [the mutations] are fully understood regarding their relationship to the disease ... [it's] not practical to use a SNP chip," Beck explained in an email. "There is a pseudogene for GBA that can make pulling out the true GBA gene sequence difficult and give misreads... so one has to develop a particular strategy [such as] amplify[ing] the gene first and then use sequencing primers."
Assays that typically detect the genes generally use either whole blood samples or saliva samples. While preferring to use whole blood samples since it plans to collect the DNA as part of the POP's larger database, the PF aims to be flexible in terms of choosing the sample type.
Beck estimated that, on average, an assay costs about $1,000 per test and per gene. In addition, results for current tests require a minimum of three weeks, and turnaround time can be anywhere from 21 to 45 days.
"There's currently no treatment for Parkinson's that will alter the course of the disease, [as] everything is symptomatic treatment, which is another reason why we're so excited to facilitate clinical trials that might alter the course of Parkinson's disease in some people," Beck added.
The foundation believes that it can act as a facilitator for pharmaceutical companies with clinical trials and people with Parkinson's disease who want to know more about their status and possibly enroll in future clinical trials. The group additionally wants to reach out to thousands of people genetically predisposed for Parkinson's disease in order to provide improved long-term outcomes.
Before the initiative, the majority of CLIA/CAP-accredited clinical labs have not offered a combined assay to patients. Individuals living with Parkinson's disease must visit at least two different sources in order to have their DNA sequenced and determine whether they either had LRRK2 or GBA-based Parkinson's disease, which may also require multiple costly follow-up tests to confirm the mutation.
Alcalay said that multiple labs do offer targeted sequencing of GBA for known mutations in certain populations like Ashkenazi Jews, about 6 to 9 percent of whom carry a common GBA mutation. However, he emphasized that "if researchers want to perform a [comprehensive] study on GBA, they need to fully the sequence the gene," in order to cover the variety of mutations that could cause GBA-related Parkinson's disease in the general population.
Beck pointed out that when individual labs offer specific diagnostic services for Parkinson's risk detection, they will fragment the diagnostic space for patients who are uncertain about their genetic risk. He emphasized that "it's not to anyone's benefit for a single company to genotype a small amount of people for a single gene," especially if the results come out negative.
The Parkinson's Foundation has therefore established a scientific advisory board to help identify firms that will ideally detect both genetic mutations and will work with the foundation to find a customized solutions for patients. As a non-profit, Parkinson's Foundation is ensuring that the donations it receives will be directed toward diagnosing and treating as many patients with a genetic risk for Parkinson's disease.
Beck said that preliminary reports estimate that over 800,000 individuals in the US have a form of Parkinson's disease, while approximately 60,000 new cases are diagnosed each year. He estimates that about 80,000 patients currently visit PF's centers and the foundation hopes to scale the number in a meaningful way with the Genetic Initiative.
Beck also plans to announce the initial Centers of Excellence that the foundation will include as part of the initiative by the end of 2018.
"While it will be a multi-year study, we currently have no time estimates [for completion], as it will depend on what we see in the community and our partners," he added.
In addition to genetic screening, the foundation will also offer separate genetic counseling to patients willing to discuss their options for treatments and lifestyle with the disease. Neurologists at the Centers of Excellence trained to work with individuals with Parkinson's disease will advise patients on how to treat their specific form. The group believes that the initiative will improve enrollment in clinical trials for Parkinson's treatment and help facilitate the use of genetic information to expand research.
"What's unique about this protocol is that we are not just treating patients as research subjects, but are engaging them by having them get their results back and see how it affects their treatment and enrollment in clinical trials," Alcalay explained. "[This program] is basically the first time in Parkinson's that the major focus is patient engagement."