Treatment of Friedreich’s ataxia using novel ferroptosis inhibitors

Ferroptosis, a form of cell death driven by excess iron, was discovered in the Stockwell Lab in 2012. Since this discovery, ferroptosis has been implicated in a variety of diseases, including Friedreich’s Ataxia (FA). The pathology of FA involves iron dysregulation and therapies that inhibit ferroptosis could counteract damage to the body in FA. Previous work demonstrated that the ferroptosis inhibitor Ferrostatin-1 (Fer-1) is protective in a variety of disease models. However, fer-1 is unstable, necessitating the development of better drug candidates. Dr Stockwell and his group thus have created analogs of fer-1 with improved drug-like properties, including better stability and brain penetration. These compounds have been further evaluated in mice, demonstrating good tolerability. To evaluate the effectiveness of these compounds for FA, various assays will be performed both in FA cell models and in tissues of FA mice. These studies will both advance our understanding of ferroptosis in FA and potentially yield a drug candidate that treats the heart and the nervous system through a new mechanism.