Study Rationale:
There is mounting evidence for involvement of mitochondrial biology in the pathogenesis of Parkinson’s disease (PD). Alterations in mitochondrial dynamics and distribution have been reported in neurons of PD brains. Regulation of Miro1, a mitochondrial outer membrane protein, is a prerequisite for mitochondrial quality control. Recent studies have focused attention on the critical role of Miro1 in PD pathogenesis and considered it as a novel target to fight PD. Thus, we are motivated to study compounds that modulate the function of Miro1.
Hypothesis:
We hypothesize that compounds that modulate Miro1 regulation have the potential for PD treatment.
Study Design:
We will conduct basic and pre-clinical research to discover, validate, and optimize Miro-targeting compounds. We will first validate drug candidates discovered in an academic research lab with Miro1 on human fibroblasts by using immunocytochemistry analysis. In addition, the pharmacokinetic behavior of the drug candidates will be characterized on models. We will elucidate and synthesize lead compounds.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
These innovative compounds that modulate Miro1 regulation may be a source for potential drugs to alter the Parkinson’s process.
Next Steps for Development:
Next we would conduct pre-clinical analysis in Parkinson’s models or dopamine cells derived from induced pluripotent stem cells from people with PD. These tests would help further drug development.