Participants in our September 24 ďGenetics and Parkinsonís DiseaseĒ Webinarópart of our†Hot Topics in Parkinson's Disease†Research Seminar Seriesóhad a lot of questions, and understandably so. Anyone who has Parkinsonís disease (PD) or a relative with PD has a vested interest in its genetics.
Our panel of Michael J. Fox Foundation (MJFF) Contributing Editor†Dave Iverson;†Dr. Andrew Singleton, senior investigator with the National Institute on Aging and a member of the MJFF Scientific Advisory Board; Elise Bendik, genetic counselor at the University of Miami Miller School of Medicine; and Dr. Brian Fiske, MJFF vice president of research programs, gave an overview of what is currently known about geneticsí role in Parkinsonís disease (PD). Check out the Webinar now on demand.
While they answered many questions, more rolled in after the Webinar. Brian helped us respond:
What is my genetic risk of Parkinsonís?
For most people, this is a hard question to answer. Currently, we can link less than about five percent of Parkinsonís cases directly to a genetic mutation. In some populations, these mutations may account for a relatively larger proportion of Parkinsonís cases, such as in individuals of Ashkenazi Jewish and Basque heritage who have a much higher chance of carrying a mutation of the LRRK2 gene. But in general, most cases of Parkinsonís probably result from a combination of genetic and environmental triggers. Research is active in this area looking for additional genetic factors that could better define individual risk for PD. If you want more insight, check out our podcast with Dave Iverson and Dr. Andrew Singleton.
Should I be genetically tested?
While individual genetic testing today canít yet inform personalized treatments, it can help lead us to better therapies. Studying the genetics of PD can point researchers to pathways of disease that provide targets for new drugs that will benefit all PD patients. [Read more on this below.]
Information on genetic risk may also help researchers select participants for clinical trials. Stratifying volunteers based on characteristics like genetic risk can increase the likelihood a drug will make it through testing and get into the hands of patients sooner.
Speak with your physician and a genetic counselor if you are thinking about being genetically tested for PD. They can talk about your potential risk and what the results could mean for you and your loved ones. Your primary care physician should be able to refer you to a genetic testing facility.
The Parkinsonís Progression Markers Initiative (PPMI) study is just starting to include individuals from specific populations that are at a higher risk of carrying a genetic mutation connected to PD. These individuals will receive genetic counseling and testing for Parkinsonís-related mutations at no cost through PPMI. Learn more at https://www.michaeljfox.org/ppmi/genetics.
If most cases of Parkinsonís are not genetic, then why is it so important to study the genetics of Parkinsonís? We need treatments that can benefit everyone with PD, not just a few.
The same cellular processes that lead to genetic cases of Parkinsonís may play a role in non-genetic cases of the disease. Thatís why studying genetics is so important ó because it can lead to treatments that could benefit everyone with the disease. Hereís how:
Genes are little more than genetic recipes that our cells use to make proteins. These proteins do all the work of keeping our bodies functioning, such as processing food and energy or keeping our brain cells connected to each other and functioning. Mess with that genetic recipe and you may impact the ability of those proteins to do the work they need to do. Studying genetic cases of Parkinsonís points us to the proteins and pathways that, when dysfunctional, lead to PD. Those same proteins could play a role in non-genetic PD, too, since they could be damaged by other influences, such as environmental factors.
So studying genetics helps us to identify those participating pathways, and that, in turn, points to drugs or therapies that might be useful for all Parkinsonís patients.
Is there anything I can do to lower my chance of getting Parkinsonís if I have an increased genetic risk?
Unfortunately there are no proven prevention methods for PD at this time. Studies have highlighted factors that are associated with either greater or lesser risk of PD. For example, smoking and caffeine consumption have been associated with lower rates of Parkinson's, while head injury and pesticide exposure have been associated with higher risk. While such studies do not definitively link these behaviors and exposures to PDóand no one should take up smokingóthey do point to possible biological mechanisms that we can target for future risk-prevention or treatment strategies.
Many clinicians believe that healthy habits such as eating a nutritious diet and exercising are linked to a healthy brain. Those are universally beneficial strategies that we should all be following anyway.
How do genes interact with environment to cause Parkinsonís?
We do not yet know how environment and genetics interact to lead to PD. But by understanding the genes and environmental triggers we can look for shared mechanisms that might play a role. For example, we know that head trauma can increase risk for PD, perhaps by causing chronic brain inflammation. Similarly, there have been some genes involved in the immune system that may slightly increase risk for PD. Both suggest that we should be looking at possible inflammation mechanisms as a possible contributor to PD. This can point us to possible therapeutic approaches.
Do genetics dictate what kind of Parkinsonís disease I have?
We do know that some genetic mutations lead to earlier onset of Parkinsonís, such as in the Parkin gene. Whether genetics can explain why some people with PD have more gait problems while others experience more tremor or that some develop dementia and others donít, we still donít have a clear picture.
Right now the Foundation is leading studies to characterize differences in people that could help us understand the biological underpinnings of different kinds of PD. In fact, researchers from the MJFF-sponsored PPMI recently published on differences in protein levels in spinal fluid between gait and tremor-dominant PD populations.
You can also†register now†for our next Hot Topics Webinar, "Surgical Interventions for Parkinson's Disease," on Thursday, November 21, from 12 to 1 p.m. ET. Iverson will lead a discussion with USCF's William Marks, Jr., MD; UCLA's Jeff Bronstein, MD, PhD; and MJFF CEO Todd Sherer, PhD.