TN-401

TN-401 is an investigational gene therapy designed to treat arrhythmogenic right ventricular cardiomyopathy (ARVC), also known as arrhythmogenic cardiomyopathy (ACM), caused by mutations in the plakophilin 2 (PKP2) gene. It utilizes an adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the human PKP2 gene specifically to heart muscle cells using a cardiomyocyte-specific promoter. The therapy aims to restore normal levels of PKP2 protein, which is critical for maintaining structural integrity and cell-to-cell signaling in cardiac tissue. Preclinical studies have shown that a single intravenous dose of TN-401 can normalize heart rhythms, reverse disease progression, and extend survival in animal models with PKP2 deficiency. The drug is currently being evaluated in the RIDGE-1 Phase 1b clinical trial for safety, tolerability, and preliminary efficacy in adults with symptomatic PKP2 mutation-associated ARVC[1][2][4][5][8].