Mundisugih Juan, Kumar Saurabh, Kizana Eddy
Centre for Heart Research, Westmead Institute for Medical Research, New South Wales, Australia; Department of Cardiology, Westmead Hospital, New South Wales, Australia; Sydney Medical School, The University of Sydney, New South Wales, Australia.
Department of Cardiology, Westmead Hospital, New South Wales, Australia; Sydney Medical School, The University of Sydney, New South Wales, Australia.
Heart Rhythm. 2024 Jun;21(6):939-949. doi: 10.1016/j.hrthm.2024.02.001. Epub 2024 Feb 7.
Cardiac tachyarrhythmia presents a significant health care challenge, causing notable morbidity and mortality. Conventional treatments have limitations and potential risks, resulting in an elevated disease burden. Adeno-associated virus (AAV)-mediated gene therapy holds promise as a potential future treatment option. Therefore, we aimed to provide a measured overview of the latest developments in this rapidly growing field. PubMed and Embase databases were searched up to January 2024. Studies that employed AAV as a vector for delivery of therapeutic agents to treat cardiac tachyarrhythmia were included. Of the 26 studies included, 20 published in the last 5 years. There were 22 novel molecular targets identified. More than 80% of the included studies employed small-animal models or used AAV9. In atrial fibrillation preclinical studies, AAV-mediated gene therapy reduced atrial fibrillation inducibility by 81% (odds ratio, 0.19 [0.08-0.45]; P < .01). Similarly, for acquired and inherited ventricular arrhythmia, animal models receiving gene therapy had less inducible ventricular arrhythmia (odds ratio, 0.06 [0.03-0.11]; P < .01). This review highlights the rapid progress of AAV-mediated gene therapy for cardiac tachyarrhythmia. Although these investigations are currently in the early stages of clinical application, they present promising prospects for gene therapy. (PROSPERO registry: CRD42023479448).
心脏快速性心律失常是一项重大的医疗挑战,会导致显著的发病率和死亡率。传统治疗方法存在局限性和潜在风险,导致疾病负担增加。腺相关病毒(AAV)介导的基因治疗有望成为未来一种潜在的治疗选择。因此,我们旨在对这个快速发展领域的最新进展进行全面概述。检索了截至2024年1月的PubMed和Embase数据库。纳入了将AAV用作载体来递送治疗药物以治疗心脏快速性心律失常的研究。在纳入的26项研究中,有20项是在过去5年发表的。共确定了22个新的分子靶点。超过80%的纳入研究采用了小动物模型或使用了AAV9。在心房颤动的临床前研究中,AAV介导的基因治疗使心房颤动的诱发率降低了81%(优势比,0.19[0.08 - 0.45];P <.01)。同样,对于获得性和遗传性室性心律失常,接受基因治疗的动物模型诱发室性心律失常的情况较少(优势比,0.06[0.03 - 0.11];P <.01)。本综述强调了AAV介导的心脏快速性心律失常基因治疗的快速进展。尽管这些研究目前正处于临床应用的早期阶段,但它们为基因治疗展现出了广阔前景。(国际前瞻性系统评价注册库:CRD42023479448)