LAY SUMMARY

New ways to target mitochondrial dysfunction in FA

This study will examine novel molecular mechanisms and validate small molecules that target those molecular players for preventing cell death and dysfunction in FA. Using patient-derived induced pluripotent stem cells, Dr Chandra will generate two models—sensory neurons and cardiomyocytes—to study the pathogenesis of FA. Based on the observation that oxidative stress is a prominent feature of FA, Dr Chandra will test the hypothesis that a specific mitochondrial pathway (MIC60-Miro1 pathway) sensitive to oxidative stress underlies damage and death in neurons and cardiomyocytes of FA patients, and it can be targeted using small molecules for therapeutic intervention. In addition to targeting the MIC60-Miro1 pathway and to identify novel targets, Dr Chandra will analyze the protein landscape of FA cells and compare it with control cells to identify alterations specific to FA. These studies are expected to provide insights into the cellular mechanisms of FA and an excellent platform to explore novel targets and new directions for therapeutic development.