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Wednesday, May 31, 2017

FoxFeed Blog Getting Precise about Precision Medicine in Parkinson's

Posted by  Loren DeVito, PhD

Using the same medicine(s) to treat everyone with a given disease is the mainstay of modern medicine. Nonetheless, this "one-size-fits-all" approach doesn't always lead to outcomes patients want, as people often respond differently to the same medicine, and some may not respond at all. Researchers are working to address this challenge through "precision medicine."
Precision medicine involves tailoring therapies for individuals based on their genes, environment and/or lifestyle. You may be familiar with this approach for cancer -- unlike chemotherapy that kills cancer (and healthy) cells, successful personalized drugs instead target genetic mutations. But how might precision medicine be used to treat Parkinson's disease (PD)?
Parkinson's is a heterogeneous disorder, meaning no two individuals have the same symptoms, disease course or treatment response. If we could better understand what drives these differences, we could, in theory, develop better medicine.
As in cancer, some Parkinson's scientists believe genetic mutations may be the basis for tailored treatments. Even though known mutations account for fewer than 10 percent of total PD cases, a greater understanding of Parkinson's genetics already has led to critical discoveries believed to be applicable to all individuals with the disease. "Finding a common mechanism behind different suspected causes of Parkinson's suggests that there might also be a common means to treat or cure it," says Marco Baptista, PhD, director of research programs at The Michael J. Fox Foundation (MJFF). 
In 1997, a mutation in the alpha-synuclein gene was first linked to a family with Parkinson's. Though the mutation is extremely rare, alpha-synuclein protein clumps (Lewy bodies) are seen in the brains of nearly everyone with Parkinson's, and offer a potential target for slowing or stopping disease progression.
To date, five anti-alpha-synuclein therapies have advanced through drug development to arrive in clinical (human) testing. Other genetic mutations also are leading to treatments. LRRK2, although fairly uncommon, is the greatest known genetic contributor to PD and has inspired the development of LRRK2 inhibitor drugs expected to enter clinical trials within 18 months. Additionally, medications targeting GBA, the most common of the currently known PD genetic mutations, have made it into clinical testing. These are all examples of precision medicine.
"We will only get to true cures if we can move away from historical clinical disease definitions to one more nuanced and linked to underlying biology, genetics and pathology," said MJFF CEO Todd Sherer, PhD and co-authors in Personalized Medicine. "Truly transforming PD treatment into a precision approach will require tackling key research and regulatory challenges and the coordinated effort of the entire PD community."

Learn more about Parkinson's genetics at

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