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

Er, Teagan S. and Reinke, Daniel and Francis, Alice J. and Solomon, Tanya M. and Viola, Helena M. and Szappanos, Henrietta Cserne and Richworth, Caitlyn M. and Jenkins, Catherine and Camacho Londoño, Juan E. and Ponnuswamy, Padmapriya and McFarlane, Ciaran and Van Petegem, Filip and Hool, Livia C. (2025) Novel Peptide Therapeutics Targeting the L-Type Calcium Channel Prevent Hypertrophic Cardiomyopathy by Decreasing Mitochondrial Energetics. JACC: Basic to Translational Science, 10 (10). p. 101292. ISSN 2452302X

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Link to published document: https://doi.org/10.1016/j.jacbts.2025.04.006

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 Ca(2+) 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 alphaMHC(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 Ca(2+) channel to modify mitochondrial function and prevent HCM.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 20 Dec 2025 04:33
Last Modified: 20 Dec 2025 04:33
URI: http://eprints.victorchang.edu.au/id/eprint/1783

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