Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Feb 26, 2024; 16(2): 64-66
Published online Feb 26, 2024. doi: 10.4330/wjc.v16.i2.64
Facing ethical concerns in the age of precise gene therapy: Outlook on inherited arrhythmias
Federico Carbone, Fabrizio Montecucco
Federico Carbone, Fabrizio Montecucco, Department of Internal Medicine, University of Genoa, Genoa 16132, Italy
Federico Carbone, Fabrizio Montecucco, IRCCS Ospedale Policlinico San Martino Genoa, Italian Cardiovascular Network, Genoa 16132, Italy
Author contributions: Carbone F and Montecucco F performed research and wrote the paper.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fabrizio Montecucco, MD, PhD, Full Professor, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genova, Italy. fabrizio.montecucco@unige.it
Received: November 30, 2023
Peer-review started: November 30, 2023
First decision: December 28, 2023
Revised: January 2, 2024
Accepted: January 29, 2024
Article in press: January 29, 2024
Published online: February 26, 2024

This editorial, comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology. We here provide an outlook on potential ethical concerns related to the future application of gene therapy in the field of inherited arrhythmias. As monogenic diseases with no or few therapeutic options available through standard care, inherited arrhythmias are ideal candidates to gene therapy in their treatment. Patients with inherited arrhythmias typically have a poor quality of life, especially young people engaged in agonistic sports. While genome editing for treatment of inherited arrhythmias still has theoretical application, advances in CRISPR/Cas9 technology now allows the generation of knock-in animal models of the disease. However, clinical translation is somehow expected soon and this make consistent discussing about ethical concerns related to gene editing in inherited arrhythmias. Genomic off-target activity is a known technical issue, but its relationship with ethnical and individual genetical diversity raises concerns about an equitable accessibility. Meanwhile, the cost-effectiveness may further limit an equal distribution of gene therapies. The economic burden of gene therapies on healthcare systems is is increasingly recognized as a pressing concern. A growing body of studies are reporting uncertainty in payback periods with intuitive short-term effects for insurance-based healthcare systems, but potential concerns for universal healthcare systems in the long term as well. Altogether, those aspects strongly indicate a need of regulatory entities to manage those issues.

Keywords: Ethics, Inherited arrhythmias, CRISPR/Cas9, Gene therapy, Equitable accessibility

Core Tip: As for other diseases, inherited arrhythmias may take advantage from gene editing. Even we are still far from clinical translation, ethical issues need to be considered in order to proceed in this research field avoiding any misconduct. Off-target effects, equitable accessibility of life-saving gene therapies and economic burden for healthcare systems are key issues that need to addressed by regulatory entities.