Study Rationale: Mitochondria generate the energy needed for cells to work properly, and impaired mitochondrial function has been linked to the loss of dopamine neurons in multiple forms of Parkinson’s disease (PD). Quality control mechanisms that remove dysfunctional mitochondria are promoted by Parkin/PINK1, genes that are mutated in some people with PD. Those same quality control mechanisms are hindered by an enzyme called USP30. In this project, we will explore whether MTX325, a drug that inhibits USP30, can promote the clearance of dysfunctional mitochondria and thereby improve the overall health of dopamine neurons and help people with PD.
Hypothesis: We hypothesize that people with PD who receive MTX325 for about a month will show beneficial changes in biomarkers of mitochondrial quality control and other disease-related biomarkers, including dopamine and inflammation.
Study Design: Once we have tested MTX325 thoroughly at different doses in healthy volunteers, we will identify 20 to 30 people who have recently been diagnosed with PD for our study. After treating these individuals for about one month — some with MTX325 and others with a placebo — we will measure changes in biomarkers of mitochondrial quality control and other PD-related biomarkers. We hope to show that MTX325 has a stronger effect on the biomarkers of mitochondrial quality control and other disease-related biomarkers than does a placebo.
Impact on Diagnosis/Treatment of Parkinson’s Disease: Our study will be the first to test MTX325 in people with PD. The results could help us to understand how to identify and treat the cellular changes that lead to PD, as opposed to merely treating the disease symptoms.
Next Steps for Development: If successful, the study will allow us to do larger and longer duration studies that could eventually show that giving MTX325 early in PD can slow the progression of the disease.
Trial Phase:1