Funded Studies
Study Rationale: Parkinson’s disease (PD) is associated with the aggregation of toxic proteins, a buildup due partly to the reduced ability of lysosomes to degrade these proteins. Improving lysosome function represents a promising therapeutic target, and blood biomarkers that can reveal lysosome function would serve as a valuable tool for treatment development. Extracellular vesicles (EVs) are small, membrane-enclosed sacs that cells can secrete to help dispose of toxic proteins. Lysosome dysfunction leads to a significant increase in EV secretion, most likely as a compensatory mechanism. A tight connection therefore exists between lysosome function and EV release.
Hypothesis: We hypothesize that the abundance and contents of EVs may serve as an accurate biomarker for lysosomal activity, and that sorting the subpopulation of EVs derived from neurons will identify biomarkers specific to the brain.
Study Design: We will use cultured cells, preclincial models and human plasma samples to detect and evaluate biomarkers of lysosome function in the brain. The cell culture work will allow us to test how EV-based biomarkers change in response to treatments and analyze their correlation to lysosomal function. Working with a preclinical PD mouse model will allow us to start evaluating the biomarkers’ relevance to the disease. This connection will be further tested using plasma samples, in which we will compare the biomarker in 50 PD and LBD blood samples to samples collected from healthy volunteers.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our work will provide information on the sensitivity and specificity of biomarkers for measuring lysosome function in the brain. Identification of such biomarkers will allow identification of individuals with the most severe lysosome dysfunction and monitoring the response to treatments that target lysosome function.
Next Steps for Development: The next steps would be to perform a full analytical validation and test the use of lysosome biomarkers in treatment monitoring in collaboration with therapeutic companies. We are already in conversation with several companies and believe that a lysosome therapeutic biomarker has excellent potential for people with PD.