Parkinson's Clinical Trial Companion Navigating Clinical Trials | Page 33

Parkinson’s Disease Is Not Inevitable may influence when and how people get Parkinson’s disease. Genetics Could One Day Dictate Your Treatment Most genetic mutations associated with Parkinson’s disease raise one’s risk a small amount. Even people with higher- risk mutations will not definitely get PD. In other words, no known mutation carries a 100 percent chance of causing Parkinson’s. Researchers are studying people with mutations linked to PD but who do not exhibit symptoms to uncover protective factors (genetic or otherwise), which could lead to treatments to prevent Parkinson’s. Genetics and Environment Can Interact to Cause Parkinson’s Science is moving away from a “one-size- fits-all” treatment approach for disease. Your genetics may soon tell doctors what therapy is best for you. Clinical trials are already under way to assess whether new therapies may benefit people with genetic mutations linked to PD. Ultimately, tailoring a treatment regimen to one’s individual biology — precision medicine — brings greater likelihood of success. Certain PD Mutations Are More Common in Some Groups Some genetic mutations are more common in certain familial and ethnic groups. For example, these three mutations are of great research interest: + + SNCA: very rare mutation found in families with many PD diagnoses + + LRRK2: more common in people of Ashkenazi Jewish, Basque or North African Berber descent + + GBA: fairly common in people of Ashkenazi Jewish descent While people of other descents can carry these mutations, researchers often recruit for genetic studies from these populations because there is a greater likelihood of finding mutation carriers. Mutations May Impact One’s Type of Disease No one with Parkinson’s has the same disease experience. Even people with the same genetic mutation experience PD differently — such as being diagnosed at different ages. There are some trends, though. People with a rare type of GBA mutation, for example, are more likely to develop cognitive impairment. Scientists are studying these known genetic connections and looking for other genes or biological or lifestyle factors that While some cases of PD may be attributed more heavily to genetic mutations (SNCA, for example), for many, an environmental factor (or combination of factors) tips the scale. An old saying is that “genetics loads the gun and environment pulls the trigger.” For example, pesticide exposure can contribute to the risk of developing PD. Some studies have found those who do develop PD after contact with pesticides have genetic mutations that affect the way the body metabolizes these toxins. It’s that combination of genetic susceptibility and environmental exposure that influences disease risk. It is possible, too, that environmental factors, such as eating a healthy diet, could play a protective role. Bringing therapies from the laboratory to the pharmacy requires the participation of thousands of volunteers in clinical trials. Look at how far we’ve come in Parkinson’s genetics research in a short time, and imagine where we’ll be in another 20 years with your help. Genetic Mutations Teach Us about Disease Within the body’s cells, the role of genes is to direct the production of proteins — worker molecules that are responsible for many aspects of life, including what we look like and how our bodies function. Genetic mutations can change how much protein is made or how proteins work. This can ultimately lead to disease, such as Parkinson’s. Studying how changes in genes and proteins lead to disease allows researchers to get a better understanding of how PD develops and how we can hopefully stop it from progressing or even beginning in the first place. For example, mutations in a gene called LRRK2 are believed to increase activity of the LRRK2 protein, which is not good for our brain or other cells, and can result in PD. Scientists are developing medications, called LRRK2 inhibitors, to block these LRRK2 proteins and keep cells healthy. Chapter 3 — Genetics and Parkinson’s Research 31