Omaveloxolone: Potential New Agent for Friedreich Ataxia

Abstract

Friedreich ataxia is a slowly progressive neurodegenerative disorder leading to ataxia, dyscoordination, dysarthria and in many individuals vision and hearing loss. It is associated with cardiomyopathy, the leading cause of death in Friedreich ataxia (FRDA), diabetes and scoliosis. There are no approved therapies, but elucidation of the pathophysiology of FRDA suggest that agents that increase the activity of the transcription factor Nrf2 may provide a mechanism for ameliorating disease progression or severity. In this work, we review the evidence for use of omaveloxolone in FRDA from recent clinical trials. Though not at present approved for any indication, the present data suggest that this agent acting though increases in Nrf2 activity may provide a novel therapy for FRDA.

Lay abstract

Friedreich ataxia is a progressive neurological disorder associated with the loss of the ability to walk, loss of hand coordination and loss of speech. Patients also develop heart disease that can be fatal. The disorder results from a relative lack of the protein frataxin, which causes abnormal mitochondrial function and lack energy production and thus gives rise to the features of the disease. Recent evidence suggests that omaveloxolone may reverse some of these features, leading to stabilization of disease progression. This drug represents a potential new therapy for Friedreich ataxia.

Keywords:

• antioxidant response element
• ataxia
• cardiomyopathy
• glutathione
• Nrf2
• reactive oxygen species
• scoliosis

Acknowledgments

The authors acknowledge ongoing specific grant support unrelated to this manuscript from the NIH, US FDA, MDA, FARA, Reata Pharmaceutical, Retrotope Pharmaceutical and PTC Pharmaceutical.

Financial & competing interests disclosure

DR Lynch received/receives grant support from Reata Pharmaceutical for performance of the MOXIe trial. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.