Metabolic dysfunction in Friedreich ataxia

David Lynch, Clementina Mesaros, Elizabeth Mercado Ayon, Yi Na Dong; Metabolic dysfunction in Friedreich ataxia. Open Biol. 1 November 2026; 16 (11): 260221. doi:10.1098/rsob.260221 

This review traces that logic from the cell to the organ to the whole body. The same map defines a compact panel of blood-based biomarkers, anchored on frataxin protein itself and extended by chain-resolved ceramides and by the succinate : fumarate, BHB : acetoacetate, NAD+ : NADH and GSH : GSSG ratios. It also nominates targets that do not require restoration of frataxin, including NRF2 activation, ferroptosis inhibition, NAD+ and sirtuin repletion, PPARgamma agonism, anaplerosis and ketone-based therapy. Reframing FRDA as a disorder of fuel logistics, rather than of fuel combustion alone, explains why a globally reduced protein produces a selective yet multisystem disease.