At the 33X dose, there was a decrease in ejection fraction, consistent with cardiac toxicity. In summary, there is a substantial survival and cardiac benefit in AAV-mediated expression of frataxin above the normal physiological level achieved at the 10X reference dose in the MCK mouse model of Friedrich’s ataxia, but toxicity at high doses. This provides a rationale for ascending the dose in human clinical studies, but with caution regarding toxicity.