Study Rationale: Recent studies have demonstrated that the brains of people with Parkinson’s disease (PD) show a buildup of toxic proteins that is due to an impairment in the brain’s waste clearance mechanisms. Disruptions in sleep, which are common in people with PD, have similarly been shown to contribute to the accumulation of toxic proteins in the brain. In this study, we will use a preclinical animal model of PD to investigate how enhancing a particular phase of the sleep cycle can promote natural brain clearance pathways, resulting in the reduction of toxic proteins in the brain.
Hypothesis: We hypothesize that drugs that enhance the “slow wave” phase of the sleep cycle will boost the brain’s waste clearance mechanisms and facilitate the removal of toxic proteins, thereby preventing or delaying the onset of PD.
Study Design: In this study, we will use a new animal model of PD to test a number of drugs that can alter slow-wave sleep, the sleep phase that promotes brain clearance mechanisms. To determine if enhanced brain clearance can improve PD symptoms, we will assess three key outcomes: enhancement of movement skills, changes in brain clearance pathways as determined using magnetic resonance imaging and the removal of toxic proteins from the brain.
Impact on Diagnosis/Treatment of Parkinson’s disease: This project will test clinically relevant drugs and repurpose them to determine if they can alter the removal of toxic waste proteins involved in PD. Positive findings will translate directly to clinical trials aimed at preventing or slowing the progression of PD.
Next Steps for Development: If successful, our findings will be directly translatable into clinical trials that test whether sleep modulation can limit the buildup of toxic proteins in PD. Importantly, the drugs being tested here are already approved or have been through the clinical trial process, allowing a direct path to therapeutic application.