Abstract highlights: This preclinical study identified a therapeutically effective dose of AAVrh10 expressing human FXN (AAVrh.10hFXN) that has the potential to be clinically relevant for the treatment of the cardiac manifestations of FA. Assessment by echocardiography demonstrated that a dose of 1.8x1012 gc/kg (qPCR determined) led to a beneficial outcome with significant improvement in ejection fraction and fractional shortening compared to untreated mice. This dose mediated a 21.5 % improvement in mortality. In nonhuman primates, the levels in the heart were comparable to levels in the range estimated necessary to convert the FA homozygote to an FA heterozygote, which based on prior research, present no clinical manifestations of FA.
Friedreich’s ataxia (FA) cardiomyopathy program will be presented at the 25th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), which is being held live in Washington, D.C. and virtually from May 16-19, 2022.
