Parkinson's Genetics

Parkinson's Genetics

A little more than 20 years ago, scientists thought Parkinson's disease (PD) had no genetic connection. Today, scientists have linked about 10 percent of Parkinson's cases to a direct genetic cause. In addition, research has discovered changes in about 80 genetic locations that appear to influence the risk of getting Parkinson's. While this is a huge leap in our understanding of PD, we know there is much still to uncover about Parkinson's genes and their roles in disease, which can help lead us to new treatments and faster results.

Leading Genetic Targets

Genes are like recipes that make cellular proteins. When researchers identify changes in a gene linked to Parkinson's, they develop a strategy to learn as much as possible about the gene, the protein it makes and the pathways it works in. Scientists make research tools to investigate the gene and its protein. They look for ways to measure protein activity. They recruit people with the mutation to learn more about its biology and clinical appearance. All these steps lead them toward discovering drug targets and testing new therapies that could help people with Parkinson's.

Today the field is studying a number of leading genes and their proteins:

SNCA (Alpha-synuclein)

In 1997, researchers at the National Institutes of Health made the first Parkinson's genetic connection, discovering that mutations in the SNCA gene were common in several families who had many members with Parkinson's. While mutations in this gene are rare, they have taught us invaluable information about PD.

The SNCA gene instructs the body to make the protein alpha-synuclein, which for reasons that are not yet known, clumps in the brain cells of people with PD. Study of the SNCA gene led to this understanding that applies to nearly all people with the disease. Since then, alpha-synuclein has been a major target of new drugs for Parkinson's.

The Michael J. Fox Foundation (MJFF) has made significant investments in research to understand alpha-synuclein and to translate those discoveries into therapeutic strategies for advancing a cure for PD. Our areas of focus include understanding its role in Parkinson's, creating tests to measure alpha-synuclein and pushing therapies into and through clinical testing. Today, a number of treatments against alpha-synuclein are in clinical trials.

LRRK2 (LRRK2 protein)

Another gene that plays a role in Parkinson's is LRRK2, which accounts for one to two percent of all cases. For people of particular ethnic backgrounds — Ashkenazi (Eastern European) Jewish and North African Berber descent — mutations in the LRRK2 gene account for a much greater number of cases than in the general PD population. Mutations in LRRK2 lead to too much activity of the LRRK2 protein, though recent research indicates people without a mutation can also have overactivity of LRRK2.

The first human study of a LRRK2 drug began in 2017. MJFF's innovative approach to bring research groups together early on — sharing resources and troubleshooting common problems — was critical to this advancement. Today, the Foundation continues to unite the greatest minds in this area toward deeper understanding of LRRK2's role in Parkinson's disease and new therapies.

GBA (GCase)

Mutations in the glucocerebrosidase beta (GBA) gene are the most common of the currently known PD genetic mutations and also more common in people of Ashkenazi Jewish descent. GBA mutations increase a person's risk of Parkinson's, but less so than mutations in SNCA or LRRK2. The GBA gene instructs production of the glucocerebrosidase (GCase) protein, and mutations are associated with not enough GCase activity.

The Michael J. Fox Foundation has long supported work in GBA. Among many investments, the MJFF-led landmark Parkinson's Progression Markers Initiative (PPMI) study is recruiting and following people with a GBA mutation (either with or without PD) to learn more about how Parkinson's unfolds in this population. (PPMI is also following SNCA and LRRK2 mutation carriers.)

PRKN (Parkin)

A common genetic contributor to young-onset Parkinson’s (diagnosed before age 50) is a mutation in the PRKN gene, which manufactures the parkin protein. Scientists believe the parkin protein plays a role in recycling mitochondria, or the “power plants” of cells. In the same pathway with parkin lies PINK1 — another target where researchers may be able to intervene to boost parkin activity.

MJFF is supporting a growing base of research to investigate PRKN, parkin and PINK1. Our strategy involves funding new and varied treatment approaches and establishing their safety; creating parkin and PINK1 measurement tools; and expanding biological understanding of PRKN dysfunction.

Genetic Risk for Parkinson's Disease

If you have a genetic mutation associated with Parkinson's, will you get the disease? Not necessarily. Some mutations carry a greater risk, but none bring a 100 percent chance of developing Parkinson's disease. There are many Parkinson's risk genes where a mutation means a very small increased likelihood of Parkinson's. Researchers are looking for other factors (environmental factors or other genetic mutations, for example) that either push or protect someone with a gene mutation to or from having Parkinson's. Your doctor and/or a genetic counselor can discuss the risk associated with different Parkinson's genes and what your results may mean for you and your loved ones.

Helping Research Efforts

People with Parkinson's and their loved ones have a critical role to play in the pursuit of a cure by being genetically tested and participating in clinical research. Learning one's genetic status is a personal choice made in discussion with loved ones. If you do decide to be genetically tested, sharing your information (stripped of any personally identifying information) with researchers can help uncover more genetic links to Parkinson's and drive therapies to slow or stop disease progression.

The Michael J. Fox Foundation is funding numerous studies to help speed discovery and be part of the genetics revolution under way in Parkinson's research. The Parkinson's Progression Markers Initiative (PPMI) has enrolled people with a GBA or LRRK2 mutation. 

PPMI is providing genetic testing and counseling for select individuals, including individuals of Ashkenazi Jewish heritage. This includes people with a parent, sister or brother, or child with Parkinson’s disease.

This resource was made possible by Prevail Therapeutics and Biogen. Partner support allows us to furnish high-quality educational content to the Parkinson’s community while maintaining our commitment to allocate donor dollars to high-impact research. The Michael J. Fox Foundation is solely responsible for the content on this page.