Viral gene transfer is able to revert phenotypical manifestation of recessive Catecholaminergic Polymorphic Ventricular Tachycardia in highly symptomatic adult knock-in mice.

MARCO DENEGRI; ROSSANA BONGIANINO; FRANCESCO LODOLA; SIMONA BONCOMPAGNI; LIU NIAN; JOSÉ EVERARDO AVELINO-CRUZ; VERONICA CELESTE DE GIUSTI; ANTONIO CURCIO; LAURA PIETRANGELO; LAURA VILLANI; FELICIANO PROTASI; ALBERTO AURICCHIO; CARLO NAPOLITANO; SILVIA G. PRIORI

Congreso; American Heart Association (AHA) Scientific Sessions 2013; 2013

Introduction. We previously demonstrated that viral gene transfer of WT-CASQ2 in neonates CASQ2-R33Q-knock-in mice is able to prevent development of recessive Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a life threatening arrhythmogenic disease. Hypothesis. We investigated whether the WT-CASQ2-gene delivery is able to revert the arrhythmic phenotype in adult CASQ2-R33Q transgenic mice with a fully blown form of the disease. Methods. Adult CASQ2-R33Q mice were instrumented with ECG telemetry to test arrhythmias susceptibility in vivo after -adrenergic stimulation. Thereafter, mice were divided in two groups: 1) mice infected with adeno-associated-viral-vector-9 (AAV9) containing the coding sequence of WT-CASQ2 co-expressed with GFP gene, and 2) negative control mice injected with sterile saline (PBS). Two months later we evaluated the effects of the infection by in vivo ECG recording, in vitro electrophysiological and molecular assays. Results. ECG was recorded in adult CASQ2-R33Q mice after epinephrine (2mg/kg) administration: 20/23 mice (87%, p