Gene Therapy in Cardiology: Is a Cure for Hypertrophic Cardiomyopathy on the Horizon?

Elizabeth D Paratz; Juan Mundisugih; Stephanie J Rowe; Eddy Kizana; Christopher Semsarian

doi:10.1016/j.cjca.2023.11.024

Gene Therapy in Cardiology: Is a Cure for Hypertrophic Cardiomyopathy on the Horizon?

Can J Cardiol. 2023 Nov 25:S0828-282X(23)01951-7. doi: 10.1016/j.cjca.2023.11.024. Online ahead of print.

Authors

Elizabeth D Paratz¹, Juan Mundisugih², Stephanie J Rowe³, Eddy Kizana⁴, Christopher Semsarian⁵

Affiliations

¹ Baker Heart and Diabetes Institute, Prahran, Victoria, Australia; St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, Melbourne University, Parkville, Victoria, Australia. Electronic address: elizabeth.paratz@baker.edu.au.
² Centre for Heart Research, Westmead Institute for Medical Research, Westmead Clinical School, University of Sydney, Westmead, New South Wales, Australia; Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.
³ Baker Heart and Diabetes Institute, Prahran, Victoria, Australia; St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, Melbourne University, Parkville, Victoria, Australia.
⁴ Centre for Heart Research, Westmead Institute for Medical Research, Westmead Clinical School, University of Sydney, Westmead, New South Wales, Australia.
⁵ Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, University of Sydney, Camperdown, New South Wales, Australia.

PMID: 38013066
DOI: 10.1016/j.cjca.2023.11.024

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy worldwide, affecting approximately 1 in 500 individuals. Current therapeutic interventions include lifestyle optimisation, medications, septal reduction therapies, and, rarely, cardiac transplantation. Advances in our understanding of disease-causing genetic variants in HCM and their associated molecular mechanisms have led to the potential for targeted therapeutics and implementation of precision and personalised medicine. Results from preclinical research are promising and raise the question of whether cure of some subtypes of HCM may be possible in the future. This review provides an overview of current genetic therapy platforms, including 1) genome editing, 2) gene replacement, 3) allelic-specific silencing, and 4) signalling pathway modulation. The current applicability of each of these platforms within the paradigm of HCM is examined, with updates on current and emerging trials in each domain. Barriers and limitations within the current landscape are also highlighted. Despite recent advances, translation of genetic therapy for HCM to clinical practice is still in early development. In realising the promises of genetic HCM therapies, ethical and equitable access to safe gene therapy must be prioritised.

Publication types

Review