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

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. Copyright � 2023 The Authors. Published by Elsevier Inc. All rights reserved.