AAV-PKP2 gene therapy

AAV-PKP2 gene therapy is an adeno-associated virus (AAV) vector-based gene replacement therapy designed to treat arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by mutations in the plakophilin-2 (PKP2) gene. Developed by Alexion Pharmaceuticals (a subsidiary of AstraZeneca), this specific program utilizes a novel cardiotropic capsid and a codon-optimized expression cassette to deliver a functional copy of the PKP2 gene to cardiomyocytes. By restoring PKP2 protein expression, the therapy aims to stabilize desmosomal structures, prevent cardiac remodeling, and mitigate the risk of life-threatening arrhythmias and heart failure. Preclinical studies in mouse models and non-human primates have demonstrated that this optimized approach provides superior cardiac transduction and protein expression compared to first-generation AAV9-based vectors, potentially allowing for lower, safer, and more efficacious clinical dosing.

Other names

PKP2 gene therapyPKP-2 gene therapyPKP 2 gene therapyAAV-mediated PKP2 gene replacement