This grant builds upon the research from a prior grant: Discovery of Translational Pharmacodynamic Biomarkers and Biomarkers of Endo-lysosomal Pathway Pathology by Biased & Unbiased Lipidomics and Metabolomics
Study Rationale: The endolysosomal system in living cells is comprised of small, specialized structures that contain enzymes that degrade proteins and remove molecular waste. Impaired function of this system leads to a build-up of toxic proteins and neurodegenerative disorders such as Parkinson’s disease (PD). Our mission is to discover therapeutics that improve the impaired function of the endolysosomal system to benefit people with PD. Identifying biomarkers (or indicators) of successful target and pathway manipulation is key in drug discovery. We are proposing a large-scale study of small molecules, commonly known as metabolites, to identify biomarkers that accelerate our drug discovery efforts.
Hypothesis: We hypothesize that we can discover biomarkers that reflect successful manipulation of the endolysosomal pathology. Use of such biomarkers will transform our ongoing efforts in drug discovery efforts and the development of therapeutics.
Study Design: Working with models of endolysosomal pathology in PD and samples from people with PD and healthy volunteers, we will use powerful technologies to identify metabolites that provide signatures of our drug discovery target and of endolysosomal pathology. We will then test our biomarkers using small chemical compounds that we are optimizing in our drug discovery efforts.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, the proposed studies will accelerate our ground-breaking drug discovery efforts to find new therapeutics that improve endolysosomal function and slow progression of PD and potentially other neurodegenerative diseases.
Next Steps for Development: Currently there are disease modifying treatment for PD. Novel therapeutics that improve endolysosomal function would likely benefit people with PD.