Omaveloxolone, But Not Dimethyl Fumarate, Improves Cardiac Function in Friedreich's Ataxia Mice With Severe Cardiomyopathy

Omaveloxolone, But Not Dimethyl Fumarate, Improves Cardiac Function in Friedreich's Ataxia Mice With Severe Cardiomyopathy Lili Salinas BA , Francisco Figueroa BS , Claire B. Montgomery BS , Phung N. Thai PhD , Nipavan Chiamvimonvat MD , Gino Cortopassi PhD , and Elena N. Dedkova DVM, The Journal of the American Heart Association (JAHA): Cardiovascular and Cerebrovascular Disease doi:10.1161/JAHA.124.038505 

 In conclusion, we determined that omaveloxolone was much more effective in recovering cardiac contractile dysfunction in FXN‐cKO mice as compared with DMF. However, neither of the drugs improved structural derangements, fibrosis, hypertrophy, or improved survival rates. These data suggest that omaveloxolone, but not DMF, could improve cardiac contractile performance and potentially enhance the quality of life in FA patients with a late‐stage cardiomyopathy. Importantly, we noticed that cardiac function was impaired significantly more in FXN‐cKO males versus females; however, omaveloxolone‐treated FXN‐cKO females started dying sooner as compared with vehicle‐treated animals. This observation is highly important and suggests that women living with FA may experience negative side effects of Skyclarys and therefore, may require dose adjustment. It is possible that omaveloxolone overstimulating Nrf2 signaling in FXN‐cKO female mice led to a shift in redox potential into a too reduced state

Omaveloxolone, But Not Dimethyl Fumarate, Improves Cardiac Function in Friedreich's Ataxia Mice With Severe Cardiomyopathy