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.
Wednesday, May 17, 2023
Dose-Dependent Cardiac Responses to Intravenous AAVrh.10hFXN Treatment of the MCK Murine Model of Friedreich’s Ataxia
363 Dose-Dependent Cardiac Responses to Intravenous AAVrh.10hFXN Treatment of the MCK Murine Model of Friedreich’s Ataxia; Dolan Sondhi, Alessandria Greco, Nicholas C. Gorman, Bishnu P. De, Isabelle Wilson, Melissa Yost-Bido, Rachel Spokony, Neil R. Hackett, Stephen M. Kaminsky, Richie Khanna, Ronald G. Crystal;(LEXEO Therapeutics, Inc). May 01, 2023 Volume 31Issue 4Supplement 1S1-794 26th Annual Meeting of the American Society of Gene & Cell Therapy
