Novel Peptide Therapeutics Targeting the L-Type Calcium Channel Prevent Hypertrophic Cardiomyopathy by Decreasing Mitochondrial Energetics.

Abstract

Mitochondrial dysfunction is considered to drive the development of hypertrophic cardiomyopathy (HCM). In search of a preventative HCM therapy, we explored the efficacy of amino acid peptide variants that could alter the L-type Ca²⁺ channel's regulation of mitochondrial energetics. We confirmed that 3 of the 4 variant peptides bound with high affinity to the beta subunit. In vivo treatment of cTnI-G203S and αMHC^403/+ mice with the peptide variants prevented the development of HCM and improved contractile function. Here, we describe a novel therapy that uniquely targets the L-type Ca²⁺ channel to modify mitochondrial function and prevent HCM.