A TAT-Frataxin fusion protein increases lifespan and cardiac function in a conditional Friedreich's Ataxia mouse model

Friedreich’s Ataxia (FRDA) is the most common inherited human ataxia and results from a deficiency of the mitochondrial protein, frataxin, which is encoded in the nucleus. This deficiency is associated with an iron-sulfur (Fe-S) cluster enzyme deficit leading to progressive ataxia and a frequently fatal cardiomyopathy. There is no cure. To determine if exogenous replacement of the missing frataxin protein in mitochondria would repair the defect, we used the TAT protein transduction domain to deliver human frataxin protein to mitochondria in both cultured patient cells and a severe mouse model of Friedreich’s Ataxia.