Increased understanding of Parkinson's disease genetics has energized drug development over the past 15 years and continues to form the basis for new treatments. Though few people get Parkinson's directly from a genetic mutation, what researchers learn from the biology of people with these mutations could lead to new therapies that could help all those with the disease. Individuals with certain genetic mutations -- with and without Parkinson's disease -- can help speed discovery and be part of the genetics revolution under way in Parkinson's research.
For years, scientists thought there was no genetic basis for Parkinson's. Then, in 1997, researchers at the National Institutes of Health discovered that mutations in a gene called SNCA (which encodes alpha-synuclein) were common in several families with a high prevalence of Parkinson's. Since then they have identified a handful of other genes that are associated with Parkinson's.
However, only about 10 percent of Parkinson's cases have been linked to a genetic cause. Most cases of Parkinson's are called idiopathic or sporadic, meaning the cause is unknown, and researchers believe onset is due to a combination of genetic and environmental factors.
Another gene that plays a role in some people's Parkinson's is LRRK2. In 2004, scientists discovered a mutation in the LRRK2 gene that caused parkinsonism in several families in North America and Europe. LRRK2 has emerged as the most common, known genetic contributor to Parkinson's, accounting for one to two percent of all cases. For people of particular ethnic backgrounds -- Ashkenazi (Eastern European) Jewish, North African Arab Berber and Basque -- mutations in the LRRK2 gene account for a much greater number of Parkinson's disease cases than in the general populations. Researchers don't know why this is yet, but they are trying to find out.
In short: not necessarily. We know that some people have mutations in the SNCA or the LRRK2 gene and never develop Parkinson's symptoms.
In addition, there are Parkinson's risk genes where a mutation means an increased likelihood of Parkinson's (not a direct causal link). 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/from having Parkinson's.
Genes are like recipes that make proteins. The SNCA gene instructs the body to make the protein alpha-synuclein , which for reasons that are not yet known clumps in certain brain cells of all Parkinson's patients. Study of the SNCA gene led to this understanding that applies to all people with the disease, and, since then, alpha-synuclein has been a major target of new drugs for Parkinson's. Research into Parkinson's genetics can unveil proteins and cellular pathways involved in the disease, which most likely play a part in idiopathic Parkinson's, too.
When researchers identify a Parkinson's gene, a strategy begins 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. They look for biomarkers to measure its activity. They recruit people with the mutation to learn more about its biology and clinical appearance. All these steps lead them toward discovery of a drug target and testing of a new therapy.
There is a critical role for Parkinson's patients and their loved ones to play in the pursuit of a cure by being genetically tested and participating in clinical research. As a research organization working to speed a cure, The Michael J. Fox Foundation would like to see people with Parkinson's genotyped to build our base of information about PD genetics.
That said, the decision to find out one's genetic makeup and disease risk is a personal one, and it is important to discuss with your family and health care provider. Also consult with a qualified genetic counselor both before and after receiving your results to understand all of the issues involved.
For now, learning your Parkinson's genetic status does not change your personal prevention or treatment regimen. But by coming together, people with certain mutations can help speed discovery and make a significant contribution to Parkinson's drug development.
Finally, remember that having a genetic mutation associated with Parkinson's does not mean you will get the disease.
Most clinical research into the genetics of Parkinson's focuses on the LRRK2 mutation because there are more known populations with this risk factor.
The Parkinson's Progression Markers Initiative (PPMI) is recruiting individuals of certain populations or descent -- Ashkenazi (Eastern European) Jewish, North African Arab Berber and Basque -- who have Parkinson's or have a relative with Parkinson's. PPMI is a study to identify Parkinson's biomarkers: objective measure of disease risk, onset or progression. Individuals from those ethnic groups are eligible for testing for the LRRK2 genetic mutation at no cost. Based on the results, some individuals will be invited to undergo further evaluation and participate in the five-year study.
Whether or not you have Parkinson's disease, you can participate in research through Fox Insight, an online observational study and digital platform that collects insight into the lived experience of Parkinson's. Study participants share information about their symptoms, overall medical history, family neurological history and quality of life through confidential online surveys. By studying the responses of thousands of volunteers over time, researchers hope to prioritize patient needs and better understand disease progression. Fox Insight ultimately aims to direct scientists to new therapies and treatments for people with PD.
For more studies looking at LRRK2 mutations -- or for all Parkinson's research studies -- visit Fox Trial Finder. You can search for studies and/or make a profile and be matched with clinical studies in your area that you may be interested in.