Omaveloxolone: a groundbreaking milestone as the first FDA-approved drug for Friedreich ataxia

Omaveloxolone represents the first FDA-approved drug for Friedreich’s ataxia (FA).Omaveloxolone targets nuclear factor erythroid 2-related factor 2 (NRF2), which is a master regulator in the antioxidant pathway.The omaveloxolone clinical trial serves as an example for future design of clinical trials.A resolutive cure for FA would probably be achieved only via combinatorial therapy. Friedreich ataxia (FA) is an inherited autosomal recessive neurodegenerative disease (NDD) characterized primarily by progressive sensory and spinocerebellar ataxia associated with hypertrophic cardiomyopathy. FA is due to an intronic GAA repeat expansion within the frataxin gene (FXN) leading to reduced levels of frataxin (FXN) which causes mitochondrial dysfunction, production of reactive oxygen species (ROS), and altered iron metabolism. To date there is no resolutive cure for FA; however, the FDA has recently approved omaveloxolone – a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2) – as the first treatment for FA. We discuss herein the urgency to find a resolutive cure for NDDs that will most probably be achieved via combinatorial therapy targeting multiple disease pathways, and how omavaloxolone serves as an example for future treatments. Friedreich ataxia (FA) is an inherited autosomal recessive neurodegenerative disease (NDD) characterized primarily by progressive sensory and spinocerebellar ataxia associated with hypertrophic cardiomyopathy. FA is due to an intronic GAA repeat expansion within the frataxin gene (FXN) leading to reduced levels of frataxin (FXN) which causes mitochondrial dysfunction, production of reactive oxygen species (ROS), and altered iron metabolism. To date there is no resolutive cure for FA; however, the FDA has recently approved omaveloxolone – a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2) – as the first treatment for FA. We discuss herein the urgency to find a resolutive cure for NDDs that will most probably be achieved via combinatorial therapy targeting multiple disease pathways, and how omavaloxolone serves as an example for future treatments.