As a Parkinson’s Foundation Center of Excellence, Penn Medicine’s Movement Disorders Center offers specialized and multifaceted care for thousands of patients with Parkinson’s disease (PD).
Along with clinical consultation and care for movement disorders, the Center conducts research and has a leading neurogenetics testing program with related counseling services specific to Parkinson’s disease.
Genetic Factors in Parkinson’s Disease
Seven genes — GBA, LRRK2, PRKN, SNCA, PINK1, PARK7 and VPS35 — are currently known to be associated with increased Parkinson’s disease risk. A 2020 study in Nature found that 15 percent of Parkinson’s disease cases have an identifiable link to one of these genes, with GBA and LRRK2 being the most common.
Thomas F. Tropea, DO, a movement disorders neurologist and researcher at Penn Medicine, says that genetic research is ongoing, and in reality, a higher percentage of Parkinson’s disease may be related to genetics.
“While there is a single gene association in 15 percent of cases, additional changes can occur around the genome that may also alter a person’s risk,” he says.
Dr. Tropea’s research seeks to understand the overlap between PD and other neurodegenerative diseases. He studies biomarkers and genetics in order to identify individuals at risk for disease progression and motor and non-motor complications of the disease.
Penn’s MIND Initiative: Enabling Universal Genetic Testing for Patients with Parkinson’s Disease
Given the genetic factors in Parkinson’s disease, there is interest in the scientific community in developing PD therapies focused on genetic targets. Enrolling in clinical trials targeting a genetic pathway requires knowing an individual’s genetic information. But genetic testing for people with Parkinson’s disease is not widely offered as a standard of care.
Dr. Tropea and colleagues have set out to change that standard of care with an initiative known as the Molecular Integration in Neurological Diagnosis (MIND) Initiative.
In collaboration with Alice Chen-Plotkin, MD, and Vivianna Van Deerlin, MD, PhD, MIND conducts scientific research aimed at studying the molecular drivers of Parkinson’s disease to identify pathways for treatment discovery.
The MIND Initiative screens for variants in the two most common genes associated with PD risk, which are the subject of clinical trials at Penn. Individuals who carry a relevant variant within one of these genes may be eligible to enroll in these clinical trials.
“We had a number of patients who may have been eligible for clinical trials and clinical research studies in the past, yet there really was not a process for making genetic testing widely available to people with Parkinson's. This niche is an area that we have dramatically expanded,” explains Dr. Tropea.
Since there are currently no available treatments targeting genetic variants of Parkinson’s disease, Penn does not use patients’ genetic information for medical decision-making beyond clinical trials enrollment. But Dr. Tropea hopes that current work will lead to new treatments tailored to genetic changes in people with PD.
Parkinson's Disease MIND Initiative Cohort Biobank
The MIND Initiative also seeks to create the world’s largest Parkinson’s disease biobank.
The Parkinson's Disease MIND Initiative Cohort aims to include everyone with PD, not just the five to 10 percent of cases traditionally focused on by research.
“We've created a pathway for everybody here at Penn to be offered access to genetic testing and genetic counseling,” says Dr. Tropea. “And around that, we've built a genetic biobank where we collect samples from everyone in the center with Parkinson's disease.”
Every patient at Penn being treated for Parkinson’s disease is given the option to participate in the cohort. Those who consent have a blood draw or saliva collection, from which the MIND team isolate DNA and measure PD biomarkers.
“We’ve essentially transformed our clinic into a research cohort,” notes Dr. Tropea. “This can help us better match patients to therapies that are best for them,” he continues. “I'm most excited about this opportunity to continue to use this data and these samples for the next probably 10, 15, 20 years, so that we can finally figure out how to treat patients better...Maybe even find a cure.”
The MIND Initiative is an active contributor to the Global Parkinson’s Genetics Program (GP2), an international effort that seeks to genotype more than 150,000 people around the world to better understand the genetics of Parkinson’s disease.
Genetic Counseling, Testing and Disclosure for Parkinson’s Disease
The Neurology Department is home to the Penn Neurogenetics Therapy Center, which has one of the largest neurogenetics counseling programs in the country.
The program has five certified genetic counselors who exclusively meet with adults with a personal or family history of neurological disorders. Most of these neurogenetics counselors participate in research as well. One of the genetic counselors, Rachel A. Paul, MS, CGC, is fully dedicated to Parkinson’s disease clinical care and research.
Penn offers traditional pre-test genetic counseling to help patients with Parkinson’s disease and their families weigh the considerations and benefits of testing. This is typically the path for patients who have an extensive family history or develop symptoms under the age of 50.
For individuals who elect to proceed with testing, genetic counselors review what the results could mean. In the era of clinical trials, this may include an introduction to new research related to particular genetic results.
In addition, genetic counselors review potential implications of genetic results for an individual’s family members and answer any questions that arise. People with PD may pass on a genetic variant to their children. But many of the common Parkinson’s disease risk variants have incomplete or low penetrance.
“For instance, the GBA gene is the most common gene associated with Parkinson’s risk. And only a small proportion of unaffected individuals who carry a variant in this gene will go on to develop the disease,” explains Dr. Tropea. “So, there is considerable nuance around genetic testing results for PD.”
Testing a Novel Approach to Evaluate Online Genetic Counseling
The Parkinson’s disease genetics research program created an online, self-paced educational platform for pre-test genetics education.
Called IMAGINE-PD, the 15- to 17-minute program includes videos of neurogenetics professionals presenting background information about PD genetics and genetic testing and explaining the potential benefits and considerations of choosing to test.
Penn created the IMAGINE-PD platform to expand accessibility of genetic services to as many people as possible. IMAGINE-PD is designed for use by people of different educational levels and those with visual and hearing impairments. Patients also have the option to have questions answered by a genetic counselor if they prefer.
A randomized clinical trial, GETVIRTUAL-PD, compares this online pre-test educational platform to standard virtual pre-test genetic counseling. The program is evaluating the online platform’s safety, effectiveness and equivalence to a virtual visit with genetic counselors.
To date, the team has disclosed genetic results to more than 300 individuals.
“We took a lot of care to curate the material, so it provides the best information to our patients,” says Dr. Tropea. “I think this can have implications well beyond just our Parkinson’s disease population.”
If this platform is effective, the team expects to make it widely available to all patients with Parkinson’s disease being treated at the MIND Initiative and Genetic Counseling Research.
Learn more about neurogenetics testing and counseling and research at Penn
- Meet the MIND Initiative team.
- Contact us for more information about enrolling in the MIND Initiative.
- Refer a patient to the Movement Disorder Center.