Synthesis and Biological Profile of Omaveloxolone: The Cornerstone for Friedreich Ataxia Treatment
Massimiliano Cordaro1, Giulia Neri1, Shoeb Anwar Mohammed Khawja Ansari1
1Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 31 V.le F. Stagno D'Alcontres, 98166 Messina, Italy.
Abstract:
This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich's ataxia (FA), along with an analysis of the historical development and current status of the synthetic strategies for OMA production. OMA activates the nuclear factor-2-(erythroid-2)-related (Nrf2) pathway in vitro and in vivo, in both animal models and humans. The Nrf2 pathway plays a crucial role in the cellular response to oxidative stress. Furthermore, OMA has been shown to mitigate mitochondrial dysfunction, restore redox homeostasis and downregulate nuclear factor-κB (NF-κB), a key mediator of inflammatory responses. Through these mechanisms, OMA contributes to tissue protection and inflammation reduction in patients with FA. The review also highlights future perspective, focusing on the challenges associated with OMA reprofiling through innovative drug delivery approaches and its potential repurposing for diseases beyond FA.
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