Nature Cardiovascular Research
Alpha protein kinase 3 gene therapy restores heart function in mouse and human models of cardiomyopathy
Abstract Truncating variants in the ALPK3 gene (encoding alpha protein kinase 3) cause severe cardiomyopathy for which no curative treatment exists 1–3 . Here we establish an adeno-associated virus (AAV)-mediated gene replacement therapy to deliver full-length human ALPK3 . AAV- ALPK3 prevented disease in neonatal Alpk3- mutant mice and reversed established pathology in adults, with proteomic analysis demonstrating reversal of more than 95% of the molecular disease signature. Beyond ALPK3 deficiency, we explored br …