(311e) Developing a Novel Parkinson's Disease Diagnostic

Parkinson’s Disease (PD) is a debilitating neurodegenerative disorder. One of the underlying mechanisms to disease progression involves the aggregation and misfolding of proteins into Lewy Bodies, of which aggregated alpha-synuclein is the primary component. Physicians diagnose patients with PD based on motor symptoms with the average age of diagnosis being 60, however, there are no clinically-approved diagnostics that could improve the confidence of diagnosis. Patients are therefore often diagnosed and subsequently receive medication for as many as 10 years or more from experiencing the first symptoms, which can significantly reduce their quality of life. As such, development of a diagnostic to strengthen the confidence of a diagnosis is urgently needed. To this end, we synthesized over 20 different monoclonal antibodies that detect only aggregated alpha-synuclein and not monomeric alpha-synuclein or protein biomarkers associated with other neurodegenerative diseases. Of these, five antibodies were separately optimized for the development of highly specific and sensitive enzyme-linked immuno-sorbent assays (ELISA). In each of these assays, we demonstrated significant discrimination in the amount of aggregated alpha-synuclein between serum samples of PD patients in their 50s compared to healthy age-matched controls, such that in a blind study, samples from PD patients were accurately diagnosed with up to 100% accuracy, depending on the assay. Such a diagnostic platform would be an invaluable tool for physicians that could significantly improve patient quality of life and life expectancy.