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(SUPPLEMENT) Enhancing Brain Clearance Mechanisms to Limit Parkinson Disease Progression

Study Rationale: Recent evidence has shown that people with Parkinson’s disease have a buildup of toxic proteins in their brains, as a result of impaired waste clearance mechanisms. Linked to this finding is the fact that sleep disruptions are common in people with Parkinson’s, which have been shown to contribute to the accumulation of toxic proteins in the brain. In this study, we will use a pre-clinical model of Parkinson disease to investigate how enhancing a particular phase of sleep can promote natural brain clearance pathways, resulting in the reduction of toxic proteins in the brain.

Hypothesis: Here we hypothesize that enhancing a specific phase of sleep using drugs, will enhance brain clearance mechanisms and remove toxic proteins, to prevent or delay Parkinson’s disease.

Study Design: In this study we will use a new animal model of Parkinson’s disease to test a number of drugs that can alter a specific phase of sleep, called slow wave sleep, which promotes brain clearance mechanisms. To determine if enhanced brain clearance can improve Parkinson disease symptoms, we will measure three key areas, (i) movement skills in pre-clinical models, (ii) changes in brain clearance pathways using MRI, and (iii) 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 Parkinson’s disease. Positive findings will directly translate to human trials aimed at preventing or slowing the progression of Parkinson’s disease.

Next Steps for Development: Positive findings from this project will be directly translatable into human trials, to limit the buildup of toxic proteins in Parkinson’s disease through the modulation of sleep. Importantly, the drugs being tested here are already approved or have been through the clinical trial process, allowing a direct path to therapeutic application.


Researchers

  • Jason A. Howitt, PhD

    Hawthorn VIC Australia


  • Laura Helen Jacobson, PhD

    Parkville VIC Australia


  • David K. Wright, PhD

    Mebourne VIC Australia


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