Cardiotropic adeno-associated virus-based gene therapy via intracoronary delivery for nonischemic heart failure.

Heart failure (HF) remains a leading cause of morbidity and mortality with significant residual risk despite major advances in medical therapies. Development of cardiotropic vectors have allowed gene therapy to be revisited to target the molecular roots of HF to potentially improve structural cardiac remodeling and cardiac contractility on top of functional improvement offered by current standard of care therapies. In a first-in-human phase 1 trial, a cardiotropic vector gene AB-1002 targets a phosphorylation pathway responsible for calcium handling in cardiomyocytes. AB-1002 stimulates inhibitor 1 (I-1c), which functions to inhibit protein phosphatase 1 (PP1). PP1 overactivity contributes to maladaptive calcium dynamics. AB-1002 has favorable safety and efficacy profiles, potentially representing a promising new frontier in HF treatment.