In early May, the Parkinson’s Foundation presented a webinar on a genetic testing initiative called PD GENEration, featuring Dr. Martha Nance. She discussed the relevance of genetics for those with Parkinson’s disease (PD), provided an overview of the PD GENEration study, and summarized what we have learned from the initiative so far and what we hope to learn in the future. We at Stanford Parkinson’s Community Outreach viewed the webinar and are sharing our notes.  

This webinar was recorded and can be viewed here.

If you have questions about the webinar, you can contact the Parkinson’s Foundation at contact@parkinson.org.

To learn more about the PD GENEration national initiative or complete a form indicating your interest in participating, you can visit the study website.

For questions specific to the study, you can call the Parkinson’s Foundation HelpLine 800-4PD-INFO or email Genetics@Parkinson.org for more information.

Now… on to our notes from the webinar.

– Lauren

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PD GENEration – Webinar notes

Presented by the Parkinson’s Foundation

May 5, 2020

Summary by Lauren Stroshane, Stanford Parkinson’s Community Outreach

Neurologist Martha Nance spoke about the PD GENEration project, dividing her presentation into four sections:

1. Why talk about genetics in the first place? Isn’t PD mainly an environmentally-caused illness?
2. PD GENEration overview
3. What do we know so far?
4. Looking to the future

The Parkinson’s Foundation designates Centers of Excellence in the treatment and research of PD around the country. Once the PD GENEration project is past its pilot period, they hope to expand the study to roughly 50 Centers of Excellence across the US.

Genetics and PD

Of people who have PD, about 90 percent likely developed it due to environmental factors. However, about 10 percent of those with PD have a genetic component to their disease that we can detect: a variant in a particular gene that has caused them to have PD. While each PD journey is different, gaining a better understanding of the genetics underpinning PD is a starting point to understand the disease. Someday, perhaps we can use genetics to help diagnose and even treat PD.

Every cell in our body contains two entire sets of 30,000 genes. Each gene is a recipe instructing the cell in how to create a given protein. A mistake in the recipe – called a mutation if it causes a disease or a variant if it is benign – affects the end result. At least twenty genes are believed to be relevant to PD, though there may be more that we simply do not know of yet.

The project PD GENEration seeks to analyze the “top seven” most important PD genes.

In clinical practice, PD genetics are quite complicated. There are so many questions to answer:

• What genes should we test, and how do we test them?
• How do we interpret the results of the tests, differentiating between a harmless variance and a disease-causing mutation?
• How do we explain those results to patients?
• What does it mean if you have a genetic mutation? What does it mean if you DON’T have a genetic mutation?
• Who should discuss genetic test results with patients?
• What about other family members?
• Is genetic testing actually useful? Does it change a patient’s treatment, prognosis, or ability to participate in research? Does it make their life better?

The PD GENEration study

In partnership with Fulgent Labs and led by Dr. Roy Alcalay with Columbia University, the PD GENEration study analyzes 7 different PD genes, provides the results to participants either via a doctor or a genetic counselor, and then assesses the participant’s understanding and experience afterward.  

The genes being tested include:

1. GBA
2. LRRK2
3. SNCA
4. PRKN
5. PINK1
6. DJ1
7. VPS35

Study design:

• Who: Individuals with PD (up to 15,000 participants)
• What: genetic testing and genetic counseling at no cost to the participant (English and Spanish). Will also create a “bank” of DNA for future research.
• When: Next 5 years – Pilot study launched at 6 sites in Oct 2019
• Where: Parkinson’s Foundation Centers of Excellence and Parkinson’s Study Group sites

How can I learn more or sign up to participate in PD GENEration?

Visit the website.

Here you will find information about how the study works, who can participate and where, and security and confidentiality. You can also fill out an interest form to receive future updates about the project. There is also a page of Frequently Asked Questions.

Pilot sites that are already enrolling include:

• Columbia University Irving Medical Center (New York, NY)
• Struthers Parkinson’s Center at Park Nicollet (Minneapolis, MN)
• Massachusetts General Hospital (Boston, MA)
• Northwestern Medicine (Chicago, IL)
• Perelman School of Medicine at the University of Pennsylvania (Philadelphia, PA)
• University of California San Diego (San Diego, CA)

More sites will be announced in coming months.

So far, over 1,400 people have completed the online interest form, representing 49 different states as well as Canada. In 6 months, over 290 participants registered at the sites listed above, with 21 states represented.

A participant’s perspective

A member of the Parkinson’s Advisory Council, Mel Mitchell, shared his perspective on his participation in the study. When he was first diagnosed, he didn’t care why he had developed PD – he just wanted to know what to do to treat it. Over time, his priorities have shifted, and he became interested in getting involved in research. The enormous scope of the PD GENEration study appealed to him. He also felt a responsibility to others to help further our understanding of PD, and knew that researchers were relying on individuals like him in order to learn more. He found the process of participating in the study to be simple and streamlined.

Results so far

Preliminary results have found a significant number of PD-associated mutations. The GBA mutation was most common, followed by PRKN, LRRK2, and SNCA, in descending order of frequency.

The Covid-19 pandemic threw a bit of a wrench into the planned rollout of the study, but it has also provided an opportunity to expand the accessibility of the study for thousands of people with PD. They are working on an amended protocol to include telehealth visits instead of in-person visits, and cheek swab kits will be sent directly to patients’ homes.

Eventual treatments for genetic types of PD?

Currently, there are no treatments for specific genetic forms of PD. However, there will be increasing numbers of trials evaluating potential treatments for individuals with known genetic mutations. For example, Denali Therapeutics has run two Phase 1 trials looking at drugs specifically for those with the LRRK2. For people who have already undergone genetic testing and know their genetic profile, there will continue to be more and more trials in which they can participate – helping researchers to find the solution!

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Question & Answer Session

Q: I already had genetic testing through 23andMe. Is there a way I can share my gene sequencing data with the PD GENEration study?

A: What we have been doing is simply repeating the testing. The study’s tests are far more comprehensive than those available by 23andMe, which only tests for a few possible mutations for each gene that is included. For instance, some individuals who received normal results via 23andMe learned after participating in the study that they actually do have a mutation that is associated with PD, which wasn’t included in the 23andMe panel.

It’s also important to perform all the genetic testing for the study in the same lab, with the same consistent techniques, to be able to include all the results in the dataset. Fortunately, having previously undergone genetic testing does not disqualify you from participating in the PD GENEration study.

Q: I have already found out that I have a genetic mutation; should I still do the study?

A: Absolutely! It’s also possible that you may have more mutations than you were previously tested for, so it is well worth doing our testing for the study as well. Variants are not reported by the lab, only mutations that we know can cause disease. During the course of the study, if it turns out there are variants we thought were harmless, which end up correlating strongly in study participants, then patients have the option to be re-contacted and notified down the line. By studying a large group of patients throughout the country, this research has the potential to really expand our knowledge of mutations associated with PD.

Q: What are the sources of funding for this study?

A: The Parkinson’s Foundation is the main funder.

Q: Can you determine the specific symptoms that an individual with a PD-associated mutation will develop over the course of their illness?

A: Not at this point. We are hoping this study may shed some light on this. We have an inkling in some cases but there is so much we don’t know that we have to be careful not to overstate our very limited evidence at this point. Certain genetic mutations and combinations of mutations tend to cause very early onset PD, such as in one’s 20s or 30s. People with PRKN don’t tend to lose their sense of smell, do not have dementia, and tend to live a long time. They don’t have Lewy bodies. It may be an entirely different disease! Those with GBA or SNCA are sometimes prone to faster progression.

Q: Will genetic testing be made available for the family members of PD GENEration participants as well?

A: This particular study does not have the bandwidth to expand testing to family members. The best we can do is provide the individual with PD with a copy of their detailed genetic testing report, which their relative can bring with them to speak with their own physician about the wisdom of pursuing genetic testing. In those who don’t have symptoms, such as a healthy 30-year-old, it can be ethically dubious to test without a specific reason. For many of these mutations, the presence of the mutation does not 100 percent guarantee that they will develop PD. It may only increase risk by a certain percent (and we do not yet know what that percent would be). So we caution against testing just for its own sake. Not to mention, your insurance company may interpret this as being a diagnosis of PD and count it as a pre-existing condition, which can cause serious issues with future insurance coverage.

Q: Will the results of this research ever be shared with insurance companies or employers?

A: For study participants, it shouldn’t matter whether the genetic testing results are shared with an insurance company or employer; they already have been labeled with the diagnosis of PD, and the test results don’t change that.

Back to the hypothetical 30-year-old son or daughter, if they underwent genetic testing themselves in the absence of symptoms or a diagnosis, then there is concern that the genetic test results could be used against them by insurers or employers.