Tenaya Therapeutics, Inc. announced the publication of its preclinical research related to its gene therapy candidate, TN-401, in the current issue of Nature Communications Medicine. TN-401 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy being developed for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by Plakophilin-2 (PKP2) gene mutations. PKP2 mutations are the most common genetic cause of ARVC, also known as arrhythmogenic cardiomyopathy (ACM), and result in a loss of key proteins needed to maintain the structural integrity and cell-to-cell electrical signaling of heart muscle cells.

TN-401 is designed to deliver a functional PKP2 gene to heart cells where it works to restore normal protein levels in order to halt or even reverse disease after a single dose. Tenaya?s RIDGE-1 Phase 1b clinical trial of TN-401 is a multi-center, open-label study to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-401. Tenaya is currently also conducting the RIDGE global non-interventional natural history and serotype study of PKP2-associated ARVC.

Both studies are being conducted at leading centers for ARVC care. Key Findings: The paper, titled ?AAV9:PKP2 improves heart function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy,? describes results from preclinical studies in a Pkp2-deficient mouse model to understand gene therapy?s impact in both prevention mode before disease onset and in treatment mode after disease onset.

A single dose of Tenaya?s AAV9:PKP2 gene therapy: Restored normal levels of PKP2 protein expression, Led to a highly coordinated and durable correction in structural genes encoding desmosome, sarcomere and calcium handling proteins with a role in maintaining cellular integrity and function, Reduced the frequency and severity of arrhythmias, Demonstrated durable efficacy in preventing disease development, Slowed or reversed disease progression after onset, Prevented fibrotic remodeling, and Improved long-term survival. Tenaya selected AAV9 as the vector for delivery for TN-401 based on its extensive clinical and commercial safety record in thousands of patients globally and its demonstrated ability in clinical studies to broadly distribute in all regions of the human heart and to more robustly express the PKP2 gene in cardiomyocytes as compared to other vectors.