For the past decade, Parkinson’s disease researchers have relied on the experimental equivalent of using a sledgehammer to tune a guitar to test new therapies for the disease. This may be a reason clinical trials of promising neuroprotective drugs fail. But, in new research published today in Nature Parkinson’s Disease, researchers at the Djavad Mowafaghian Centre for Brain Health (DMCBH) may have found the ideal tool for the job.
“We believe we’ve found an approach that is most relevant to humans, in that our models of gene dysfunction mimic the etiology of Parkinson’s disease rather than its pathology— meaning its beginning rather than its end,” says Dr. Matthew Farrer, the study’s lead investigator and a researcher at the Centre for Applied Neurogenetics at DMCBH. “This means we’re looking at the disease before it becomes symptomatic, before it begins affecting an individual’s motor skills or cognition.”
Parkinson’s disease symptoms are associated with the progressive loss of dopamine-producing nerve cells. Over time, these cells effectively become out of tune, and eventually they stop working altogether.
Until now, the best available experimental models of the disease were based on flooding the brain with alpha-synuclein—a protein in the brain that, when it accumulates abnormally into clumps, is linked to Parkinson’s—or using neurotoxins to destroy dopamine-producing cells. These conventional models exhibit the classic motor and behavioural symptoms of the disease, which is why they have been widely adopted by the Parkinson’s field, but the sledgehammer approach to inducing the disease means the cells die—the guitar is smashed—before any of the subtle changes in the tune can be measured.
