Abstract 18712: Adeno-associated Viral Gene Delivery of Calsequestrin 2 Protects Adult Calsequestrin 2-R33Q Knock-in Mice From Developing Ventricular Tachycardias

Background. Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a highly lethal recessive arrhythmogenic disease associated with mutations in the calsequestrin 2 (CASQ2) gene. We previously demonstrated that CASQ2 gene delivery was able to rescue the arrhythmic phenotype in CASQ2 knock-out (KO) mice 5 months after the viral infection. The aim of the present study is to investigate the long-term effects of viral gene delivery in CASQ2-R33Q missense mutation mouse model. Methods. Newborn CPVT mice were infected with adeno-associated viral vector 9 (AAV9) containing the coding sequence of the wild type CASQ2 co-expressed with green fluorescent protein (GFP) gene. Furthermore, we evaluated the effect at 7 and 12 months after viral infection by in vivo ECG analysis, in vitro electrophysiological and molecular assays. Results. Telemeter recording of ECG demonstrated in vivo ventricular tachycardias (VT) after epinephrine (2 mg/Kg) administration in only 17% (2 out of 12) of the infected mice, while ...