Facing ethical concerns in the age of precise gene therapy: Outlook on inherited arrhythmias

Abstract

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.