Each year, 60,000 Americans are newly diagnosed with Parkinson’s. While it is more common among older adults, those as young as 18 years old can get it. The disease is especially problematic because it is difficult to diagnose and treat. Although therapies can alleviate the symptoms, there is no known cure. Telltale symptoms, such as tremors and problems with balance or walking, may indicate that a person has the disorder, but an absolute diagnosis can only be made through an autopsy after a patient has died, according to the American Parkinson Disease Association. Parkinson’s conditions can also mimic other diseases, so misdiagnosis is common, notes the Cleveland Clinic.
How Often Does Parkinson’s Run in the Family?
Most Parkinson’s cases have no connection to a genetic cause, but scientists have found that some gene mutations can heighten an individual’s risk. Researchers believe that a better understanding of these genes may improve ways of identifying and treating the illness. The National Institute of Neurological Disorders and Stroke reports that an estimated 15 to 25 percent of people with Parkinson’s have a family history of the disorder. The Michael J. Fox Foundation for Parkinson’s Research estimates that about 10 percent of cases are linked with a genetic cause. “Parkinson’s doesn’t stand out as a hereditary disease over and above any other chronic diseases that people deal with,” says Rebecca Gilbert, MD, PhD, chief scientific officer for the American Parkinson Disease Association in New York City. “But if you have a parent with Parkinson’s disease, you have about a fourfold greater risk over the general population.” Still, that risk is relatively small. About 1 percent of the population over 60 has Parkinson’s, according to the Michael J. Fox Foundation, and that number rises to about 4 percent for those who have a mother or father with the illness, according to Dr. Gilbert. The overall message is: Just because you have a gene linked to Parkinson’s does not mean you will get the disease.
Causal and Associated Genes
The idea that a gene abnormality may cause some cases of Parkinson’s dates back to 1997. At that time, scientists at the National Human Genome Research Institute (NHGRI) and the National Institutes of Health (NIH) first precisely identified that an irregularity in the synuclein alpha gene (SNCA), the gene that provides instructions to make the protein alpha-synuclein, could lead to this movement disorder. Alpha-synuclein is found in abundance in the brain and is thought to help regulate the release of dopamine, a chemical involved in the transmission of signals between nerve cells (neurons). With Parkinson’s, the brain doesn’t produce enough dopamine. This 1997 research on SNCA confirmed that “at least one form of Parkinson’s disease is inherited.” “Up until 1997, people did not broadly think that Parkinson’s could be hereditary or familial,” says James Beck, PhD, chief scientific officer with the Parkinson’s Foundation. “With that discovery, we began to identify a number of genes linked with Parkinson’s.” In 2004, scientists discovered the most common genetic contributor to Parkinson’s, a mutation in LRRK2, a gene that is active in the brain and pushes a person’s risk to 30 percent. Certain ethnic groups (Ashkenazi or Eastern European Jews, North African Arab-Berbers, and Basque) are more likely to have this gene irregularity. The faulty LRRK2 gene accounts for 1 percent to 2 percent of all Parkinson’s cases, according to a review published in February 2016 in Biochemical Journal. Mutations in PARK7, PINK1, and PRKN genes have also been shown to directly produce the disease. While mutations in these genes can lead to inherited Parkinson’s, research has found that alterations in some of the causal genes may also play a role in noninherited (or “sporadic”) forms of the condition. While some faulty genes directly cause Parkinson’s, others heighten the risk but do not induce the disorder outright. These associated genes include GBA and UCHL1. They are thought to combine with certain environmental factors to trigger Parkinson’s, according to the Parkinson’s Foundation. Some of these environmental elements are head injury and exposures to pesticides, metals, and solvents. “With an associated gene, there seems to be a relationship between the mutation and developing Parkinson’s disease, but the exact link is not completely clear,” says Gilbert.
Who Should Get Genetic Testing?
Two groups might consider getting genetic testing, according to Gilbert:
People with Parkinson’s who want to know if they have a mutation they may pass along to their childrenChildren and siblings of family members with Parkinson’s who want to determine their genetic risk for the disease
“Right now it’s not standard of care for everyone with Parkinson’s to get genetic testing,” she says. “The likelihood that we’re going to find one of these mutations that is known already is small, and even if you [or a family member] have a mutation associated with Parkinson’s, it doesn’t mean that you’re going to get the disease.” So, at this point, the value of getting tested depends on the individual. Doctors can provide this type of genetic evaluation, or people may turn to direct-to-consumer genetic testing, such as 23andMe. These tests, however, can be limited. “You have to be careful with those panels because they’re not very comprehensive,” says Gilbert. “They may test for only one or two gene variations.” Currently, 23andMe analyzes DNA from spit samples for a variant in LRRK2 and a variant in the GBA gene associated with the disorder. The company makes it clear that the exam does not diagnose the disease, and there are many other mutations to consider. Parkinson’s patient Paul Cannon, PhD, who works for 23andMe as its Parkinson’s research community manager, took the test and found that he had neither of the genetic variations. “In some ways, it’s good to know this because the GBA mutation is not nice to have,” he says. “A much more aggressive version of the disease is associated with the GBA mutation.” The American Parkinson Disease Association recommends that any form of genetic testing be done along with genetic counseling. “You should have someone sit with you who understands genes, who understands disease risk, and explains everything to you first, so you understand what the limitations of the test are,” says Gilbert.
Genetic Testing May Lead to a Cure
Although genetic testing can leave individuals with many unanswered questions, the data provided may further the study of the disease. “The more individuals you can work, the more things you can discover,” says Cannon. “We are interested in studying people who have a risk gene because the sooner we can learn how to stop it [the negative impact], the better off people will be.” Clinical trials are in progress to test therapies that target gene mutations, in particular GBA and LRRK2. Pharmaceutical companies conducting these studies need patients who test positive for specific gene variations. By getting tested, individuals have a chance to participate in research programs that may lead to a cure. Gilbert points out that drugs that target specific mutations may benefit a larger group of Parkinson’s patients. “The biochemical problem that happens when a person has an LRRK2 mutation might appear in someone else without an LRRK2 mutation but by another means,” she says. “So they may also benefit from medication developed for people with an LRRK2 mutation.” If you are interested in participating in a trial, the Michael J. Fox Foundation offers a roundup of the latest investigations currently being conducted and how to get involved. One 23andMe user described how her test revealed that she had the LRRK2 mutation and an ethnic background that was 85 percent Ashkenazi Jewish and about 11 percent North African Berber. She had also suffered a head injury as a young adult. Because of these high-risk factors, she signed up for five clinical trials and with a Facebook page where people with the LRRK2 mutation can share information. “Once there are mutation-specific treatments, people are going to start needing know what their gene profile is to know if they are going to be responsive to a particular drug,” says Gilbert. “This is not the reality today, but it is certainly something that is coming. It’s the way of the future.”
