Advancing a novel ASO therapy for Friedreich ataxia cardiomyopathy using a pre-clinical human vascularised cardiac organoid model

Jarmon G. Lees, Li Li, Haoxiang Zhang, Anne M. Kong, Andrew Treller, Geraldine M. Mitchell, Mirella Dottori, Alice Pebay, Stephen Wilcox, Mark Chong, Roger Peverill, Martin Delatyki, Jeffrey M. Pullin, Davis McCarthy, Jill S. Napierala, Marek Napierala, Shiang Y. Lim, Advancing a novel ASO therapy for Friedreich ataxia cardiomyopathy using a pre-clinical human vascularised cardiac organoid model, Journal of Molecular and Cellular Cardiology Plus, Volume 15, Supplement, 2026, 100527, ISSN 2772-9761, doi:10.1016/j.jmccpl.2025.100527. 

ASO-mediated knockdown of MEG3 reversed EC angiogenic dysfunction, limited SMC migration, reversed mitochondrial dysfunction, and prevented cardiac injury in a human vascularized cardiac organoid model. These findings suggest that MEG3 may be a promising novel therapy for treating cardiovascular disease in FA.

Advancing a novel ASO therapy for Friedreich ataxia cardiomyopathy using a pre-clinical human vascularised cardiac organoid model