Funded Studies
Study Rationale: Neurons keep themselves healthy and free of damaged cellular materials using an internal garbage collection system called autophagy and internal recycling centers called lysosomes. Autophagy and lysosomes become less active in all of us as we age, and human genetics shows this is especially true in at least some forms of Parkinson’s disease (PD). We currently lack drugs capable of stimulating autophagy and lysosomes without doing having other toxic effects on cells. In this project, we attempt to discover one.
Hypothesis: We hypothesize that stimulating autophagy will enhance turnover of damaged mitochondria in neurons, preventing the onset of dysfunction and death in these cells, and that early treatment with an autophagy-stimulating drug could help prevent the onset of PD symptoms.
Study Design: We will use our detailed understanding of the biochemistry of autophagy and lysosomes to identify chemical compounds that activate autophagy and increase the number of lysosomes. We will test the compounds first in simple cell biology assays, then in cultured neurons and lastly in preclinical mouse models of PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: The build-up of damaged mitochondria is considered to be a contributor to PD; activation of “mitophagy,” a major form of mitochondrial quality control, could therefore prevent the onset of PD if undertaken early.
Next Steps for Development: In the two-year time frame of the project, we hope to prove that our compounds induce autophagy and are non-toxic. If this succeeds, the next step would be to test the compounds in preclinical models of PD and obtain the data needed for an investigational new drug filing with the FDA.