Developing Novel Rna-Based Therapeutics For Parkinson'S Disease


Disease modifying therapies for Parkinson's disease (PD) remain a major unmet medical need despitenumerous large-scale clinical trials. Among the reasons for these disappointing outcomes to date is the choiceof proposed therapeutic targets that appear not to be critical for disease development or progression. But ourcurrent understanding about the molecular pathogenesis of PD has provided new therapeutic targets and theopportunity to develop disease-modifying therapies. Accumulating evidence from human genetics, cell biologyand animal model studies suggest that α-synuclein is a key protein in this disease as it misfolds, aggregatesand forms fibrils that can propagate across neurons, explaining the progressive nature of the disease and theemergence of additional disturbing symptoms including dementia. A strong driver of its pathologicalaggregation is its concentration in the brain. Accordingly, reducing the expression of α-synuclein has thepotential to mitigate downstream cascades of pathologic events and slow down neurodegeneration. Wepropose to identify small molecules that downregulate the expression of α-synuclein using a novel approachthat we have developed. Our lead identification strategy, named Inforna, is designed to target RNA and impartbiological activity. In this project, we will use Inforna to design small molecules that inhibit α-synucleinproduction, followed by optimizing these molecules for further development.
Effective start/end date12/15/1612/14/17


  • National Institutes of Health (NIH)


Parkinson Disease
Medical Genetics
Animal Models
Clinical Trials