Study Rationale: TPRML1 is protein found on lysosomes, which serve as the cell’s degradation and recycling center. Lysosomes stop working properly in Parkinson’s disease and accumulate garbage, causing cellular stress, and driving progression of disease. One strategy to restore proper lysosomal function is through drugging TRPML1, which when activated helps accelerate garbage removal & recycling by making more lysosomes and making existing lysosomes more efficient.
Hypothesis: Enhancing TRPML1 activity in the brain using a small molecule agonist could improve lysosomal function and slow the disease progression for PD patients.
Study Design: Our team has identified highly brain-penetrant and selective TRPML1-activating small molecules. In this study, we will further optimize and identify a lead compound to advance into preclinical safety studies. These studies will thoroughly assess the safety profile of the lead compound and by the end of the study demonstrate the compound is safe enough to advance into human clinical studies.
Impact on Diagnosis/Treatment of Parkinson’s disease: Current therapeutics for PD address symptoms and do not treat the underlying causes of the disease. We aim to address a key root cause of PD by advancing TRPML1 small molecule agonists to correct and enhance lysosomal function, which we believe will slow the progression of PD.
Next Steps for Development: Upon completion of this study, we plan to advance the lead compound into human clinical trials. We would first begin by dosing in a Phase 1 healthy volunteer study to confirm safety and then move quickly into Parkinson’s disease patients with the goal of provide proof of concept for slowing progression of PD.