Project Title: Enhancing brain clearance mechanisms to limit Parkinson’s disease progression

Principal Investigators: Jason Howitt, PhD; Laura Jacobson, PhD; David Wright, PhD

Institutions: Swinburne University, The Florey Institute of Neuroscience and Mental Health and Monash University

Study Rationale: The removal of extracellular alpha-synuclein via brain clearance pathways has emerged as a promising method to prevent or slow Parkinson Disease (PD). Recently, slow wave sleep has been identified as a major mechanism for activating the glymphatic and lymphatic clearance pathways in the brain for the removal of toxic neurodegenerative proteins. In this proposal the research team will test if pathogenic alpha-synuclein can be removed from the brain using four different classes of drugs that increase slow wave sleep. The proof-of-concept study will employ a novel mouse model of PD that uses exosomal trafficking of alpha-synuclein to induce disease pathology. Outcomes from this proposal will identify if therapeutically targeting slow wave sleep can reduce brain pathology and rescue motor symptoms in a PD animal model.