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Wednesday, December 7, 2016

Mutation Linked to Cognitive Problems in Parkinson’s, But Carries Hope of Treatment

DECEMBER 7, 2016 BY MAGDALENA KEGEL IN NEWS.




Researchers identified a gene that makes cognitive problems much more likely in people with Parkinson’s disease. The findings not only help to explain why some patients develop memory problems, but may also support trials leading to a more personalized treatment approaches.
“I believe this is the dawn of personalized medicine for Parkinson’s disease,” Clemens Scherzer, MD, an associate professor of Neurology who leads the Neurogenomics Lab and Parkinson Personalized Medicine Initiative at Brigham and Women’s Hospital and Harvard Medical School, and served as senior study investigator, said in a news release.
The research team at Brigham and Women’s Hospital in Massachusetts explored a gene that is known to cause Gaucher disease. This condition results when a person carries two mutated gene copies. Until reports recently began to mention that having one gene copy was linked to Parkinson’s, scientists had believed that one mutated copy made no difference.
Investigating the links between the gene and cognitive decline in Parkinson’s, the team examined 2,304 patients across the U.S., Canada, and Europe. Researchers found that 10.3 percent of these patients carried mutations in one gene copy of the glucocerebrosidase (GBA) gene.
All the patients with a flawed GBA gene had a greater risk of cognitive decline. But researchers discovered that those with particularly severe mutations — known to cause neuropathic Gaucher disease, affecting the brain — had an even higher risk:  a 217 percent increased probability over time of experiencing difficulties in their capacity to think.
Indeed, about half of the patients with severe mutations developed cognitive impairment within 10 years after receiving a Parkinson’s diagnosis, researchers found.
Since treatments for Gaucher disease have been available for more than two decades, the team now hopes that clinical trials will explore ways to prevent cognitive decline in these at-risk patients.
“Mutations in the GBA gene pathogenic for neuropathic GD [Gaucher disease] and complex alleles shift longitudinal cognitive decline in PD into ‘high gear.’ These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of [Parkinson’s] clinical trials,” the researchers wrote.
Scherzer believes that trials based on a patient’s genetic makeup are more likely to succeed than trials without specific patient selections. He thinks that inefficient trial designs may, in part, explain the many failures seen in Parkinson’s clinical studies.
“We have now launched a Consortium with The Michael J. Fox Foundation and industry to put together a toolkit for GBA-directed, molecularly targeted trials in Parkinson’s disease,” said Scherzer.
“This toolkit will be an open resource for all scientists and pharma, and will comprise gene tests, biomarkers, and clinical parameters needed for successful proof-of-concept trials in Parkinson’s disease. Smaller, more efficient trials remove a big entry barrier for pharma companies. This is good news for drug development and patients.”
http://parkinsonsnewstoday.com/2016/12/07/gene-mutation-linked-to-cognitive-problems-in-parkinsons

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