I-Corps: Repurposing Serotoninergic Compounds for Improved Treatment of Parkinson's Disease

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The broader impact/commercial potential of this I-Corps project is the development of target-specific drugs that reduce severity and incidence of levodopa-induced dyskinesia in Parkinson’s disease. Dyskinesia is a debilitating side effect of levodopa therapy characterized by abnormal involuntary movements that can interfere with daily activities present in up to 90% of nearly 10 million Parkinson’s disease patients worldwide. Considering the increased economic burden felt by caregivers and patients resulting from the development of dyskinesia, in addition to the associated reductions in quality of life, providing dyskinesia relief to patients represents a largely unmet need in the clinic. Reducing dyskinesia may allow some patients to regain more control of their lives. Some may be able to begin feeding and bathing themselves again, others may once again play with their children or grandchildren, and others may regain enough movement control to return to work. Commercially, dyskinesia relief presents an opportunity to repurpose FDA-approved drugs into patentable combinations and/or formulations that increase the likelihood of successful translation into the clinic.This I-Corps project is based on the development of newly repurposed dual-action selective serotonin (5-HT) reuptake inhibitor (SSRI)/5-HT1A receptor agonist compounds that reduce the expression and incidence of dyskinesia. Over a decade of research has validated the capability of drugs with either SSRI or 5HT1A receptor agonist actions to reduce dyskinesia, however, a breakthrough discovery has uncovered evidence that drugs acting on both targets produce an unprecedented reduction of dyskinesia exceeding 90% suppression. Fortunately for patients, two FDA-approved drugs have been identified that meet these criteria and produce substantial effects in pre-clinical models. Using repurposed, as opposed to novel, drugs increase chances of successful translation into the clinic, as these compounds already have been de-risked and trialed for safety and tolerability. In addition, the mechanisms of action of these drugs are well validated through prior trials, reducing development costs by hundreds of millions of dollars. The use of repurposed drugs is safer, cheaper, and more successful, which is why 30% of all newly-FDA approved treatments involve the use of repurposed drugs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.