遗传性心律失常的基因治疗。
Gene therapy for inherited arrhythmias.
机构信息
Department of Cardiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
Institute of Experimental and Clinical Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
出版信息
Cardiovasc Res. 2020 Jul 15;116(9):1635-1650. doi: 10.1093/cvr/cvaa107.
Inherited arrhythmias are disorders caused by one or more genetic mutations that increase the risk of arrhythmia, which result in life-long risk of sudden death. These mutations either primarily perturb electrophysiological homeostasis (e.g. long QT syndrome and catecholaminergic polymorphic ventricular tachycardia), cause structural disease that is closely associated with severe arrhythmias (e.g. hypertrophic cardiomyopathy), or cause a high propensity for arrhythmia in combination with altered myocardial structure and function (e.g. arrhythmogenic cardiomyopathy). Currently available therapies offer incomplete protection from arrhythmia and fail to alter disease progression. Recent studies suggest that gene therapies may provide potent, molecularly targeted options for at least a subset of inherited arrhythmias. Here, we provide an overview of gene therapy strategies, and review recent studies on gene therapies for catecholaminergic polymorphic ventricular tachycardia and hypertrophic cardiomyopathy caused by MYBPC3 mutations.
遗传性心律失常是由一种或多种基因突变引起的疾病，这些基因突变会增加心律失常的风险，从而导致终身猝死风险。这些突变要么主要扰乱电生理稳态（例如长 QT 综合征和儿茶酚胺多形性室性心动过速），要么导致与严重心律失常密切相关的结构性疾病（例如肥厚型心肌病），要么导致心律失常的倾向增加，同时伴有心肌结构和功能的改变（例如致心律失常性右室心肌病）。目前可用的治疗方法不能完全预防心律失常，也不能改变疾病进展。最近的研究表明，基因疗法可能为至少一部分遗传性心律失常提供有效的、靶向分子的治疗选择。在这里，我们提供了基因治疗策略的概述，并回顾了最近关于基因治疗儿茶酚胺多形性室性心动过速和 MYBPC3 突变引起的肥厚型心肌病的研究。
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