Novel Mitochondrial Targets for Friedreich’s Ataxia

In this grant proposal, Dr. Wang seeks to target the oxidative stress in FA cells in a new way. ROS (reactive oxygen species) are highly reactive molecules normally produced in the cells by many reactions, but when allowed to accumulate, as is the case for FA, they can induce damage and, eventually, cell death. Dr. Wang proposes a new therapeutic strategy for FA that, instead of reducing ROS, targets the consequences of elevated ROS inside the cell that cause cell damage. Dr. Wang and her group discovered that high ROS levels cause impairment of a mechanism that is important to recycle mitochondria and found molecules that can target this mechanism and restore mitochondrial recycling. Dr. Wang provided evidence that targeting this pathway rescues the phenotype of a fruit fly model of FA and improves survival of FA cells. With this work, she aims to validate novel therapeutic targets and test small molecules that could be translated into disease-modifying therapies.