‘Is Parkinson’s Inherited?’ MJFF Webinar Focuses on Genetics, Diversity in Trials

Forest Ray PhD avatar

by Forest Ray PhD |

Share this article:

Share article via email
Dopamine Transporter Gene Mutation

A new webinar titled “Is Parkinson’s Inherited?” — led by a research vice president at the Michael J. Fox Foundation (MJFF) — focused on the genetics and heritability of Parkinson’s disease and spoke to the need for greater diversity in clinical trials.

The MJFF’s latest Third Thursday Webinar, moderated by Brian Fiske, PhD, senior vice president of research programs, addressed the 1997 discovery of genetic mutations in several families with Parkinson’s, which spurred a massive research effort to find other genetic changes that could explain the disorder.

Since then, scientists have identified roughly 90 places within genes where changes associate with Parkinson’s but do not necessarily cause it on their own. This association challenges the traditional view that a genetic disease is one that a parent passes to their child.

Joining Fiske on the webinar panel were Ofer Nemirovsky, senior advisor of HarbourVest Partners and a member of the MJFF board of directors; Reni Winter-Evans, an MJFF research ambassador and clinical trial participant from Indiana; and Ignacio Fernandez Mata, PhD, a geneticist at the Cleveland Clinic and head of the Latin American Research Consortium on the Genetics of Parkinson’s Disease.

As Mata explains early in the webinar, “In that [sense], Parkinson’s would not be considered really a genetic disease per se, because there [are] very few cases where there’s actually a genetic variant … that, if you inherit it, you will develop the disease 100% of the time.”

Parkinson’s is genetic in that variations in genes — mutations — increase one’s susceptibility to it. Susceptibility is not certainty, however.

Even some people with gene variants that are considered “high risk,” such as those in the SNCA, LRRK2, PRKN or PINK1 genes, live into their 80s and 90s without developing Parkinson’s.

“We still don’t understand how or why some people will develop [Parkinson’s] or not,” Mata said, hypothesizing that combinations of variants, along with environmental triggers, such as pesticides and unhealthy lifestyles, may better predict Parkinson’s occurrence.

“There’s a huge combination of things that really has to happen, in most cases, for somebody to develop the disease,” Mata said.

The genetic variation between individuals complements the genetic differences found within broader groups of people. To truly understand what drives the disorder, researchers need data on whole populations of people.

As Fiske explained, this is an area in which the scientific community must improve.

“A lot of the genetics in Parkinson’s done to date has really just been in a subset of the population. In particular, European Caucasians,” he said.

Mata said this limitation affects all diseases, not just Parkinson’s.

“We believe that populations that have not been studied could be the key to identifying new genes,” Mata said, adding that “new genes mean new therapies.”

As an example of discoveries lying in wait, Mata points to a particular variation in the GBA gene that affects about 5% of Parkinson’s patients in Colombia and — at least so far — nowhere else. 

Other families with Parkinson’s that he and his colleagues follow lack variants in any of the known associated genes.

Mata says organizations such as the MJFF increasingly fund studies in underrepresented populations. More than ever, people in regions such as Africa and Southeast Asia are being recruited into studies.

Alongside genetic studies, lifestyle changes specific to different cultures will increase scientists’ understanding of environmental contributions to Parkinson’s, the researchers said.

Diversity complements large numbers, both of which are needed to conduct meaningful research.

The panel’s Nemirovsky, who has participated in studies as a Parkinson’s patient, encourages everyone who has the disease to consider both genetic testing and enrolling in clinical trials.

“The more data we have, the better,” he says.

“If you have 1,000 people who have the GBA mutation and 100 of them develop Parkinson’s, and you do an analysis and you find that the hundred only got five hours of sleep every day and the 900 always ate an avocado every morning, that would be very simple and easy to say, ok, you should eat an avocado every day and get a lot of sleep.”

While Parkinson’s admittedly is considerably more complex than Nemirovsky’s example, it points to the need for data from many people to derive meaningful conclusions.

Winter-Evans, who also has participated in trials as a Parkinson’s patient, noted that these studies also need more healthy controls to enroll. Indeed, she took action on that front herself to help: “I voluntold my husband that he needed to participate also, as a healthy control,” she said.

Family members should be encouraged to participate in trials, both Winters-Evans and the experts said, as they can provide much useful information.

“When we look at a family, we always try to look at first-, second-degree relatives, that are affected,” Mata said. “You always have to remember though, that families share environments.”

A family with a history of Parkinson’s, all living on a farm, might all be exposed to the same environmental factors, for instance. In this case, genetics may not be the culprit.

Finding family aggregations — many different people from varying generations of a family — of Parkinson’s has contributed to understanding the risk associated with different variants in genes mentioned earlier in the webinar. Mata described finding that Parkinson’s patients in the same family had different variants in the LRRK2 gene together with different kinds of protein aggregates (clumps) in their brains.

“As a researcher, that kind of blows your mind,” he said.

This wide variability in genetic causes of Parkinson’s and the prognoses associated with them, as well as evidence that the risk attached to some variants is affected by ethnicity, all reinforce the need for greater numbers and more diversity in clinical trials.

Finally, Nemirovsky and Winter-Evans discussed during the webinar the ways that their diagnoses led to changes in their personal lives.

Research linking Winter-Evans’ LRRK2 mutation to inflammation led her to incorporate food with anti-inflammatory potential into her daily life, along with regular exercise. She has experienced a positive change in her symptoms, even regaining some of her lost sense of smell.

“It’s important to be in control and to not expect your doctor or a pill to fix things,” she said.

For Nemirovsky, his diagnosis meant paying more attention to the healthy activities that are generally recommended — eating healthy, exercising regularly, and keeping stress low — and living more in the present.

“Instead of thinking or wondering where I’ll be in 10 years, or 15 years, I really try to focus on where I am now and enjoying it, and enjoying my friends and my family,” he said.

The complete webinar and both a podcast version and text transcript will be available here, after they post later this month.

The MJFF offers a free live webinar on the third Thursday of each month, discussing various aspects of living with Parkinson’s and the foundation’s work to speed medical breakthroughs. Directions for registering for the webinars can be found on the website.