Fish Kenneth M, Ishikawa Kiyotake
Cardiovascular Research Center, Ichan School of Medicine at Mount Sinai, New York, NY 10029, USA.
Discov Med. 2015 Apr;19(105):285-91.
Chronic heart failure is expected to increase its social and economic burden as a consequence of improved survival in patients with acute cardiac events. Cardiac gene therapy holds significant promise in heart failure treatment for patients with currently very limited or no treatment options. The introduction of adeno-associated virus (AAV) gene vector changed the paradigm of cardiac gene therapy, and now it is the primary vector of choice for chronic heart failure gene therapy in clinical and preclinical studies. Recently, there has been significant progress towards clinical translation in this field spearheaded by AAV-1 mediated sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) gene therapy targeting chronic advanced heart failure patients. Meanwhile, several independent laboratories are reporting successful gene therapy approaches in clinically relevant large animal models of heart failure and some of these approaches are expected to enter clinical trials in the near future. This review will focus on gene therapy approaches targeting heart failure that is in clinical trials and those close to its initial clinical trial application.
由于急性心脏事件患者生存率的提高，慢性心力衰竭的社会和经济负担预计将会增加。对于目前治疗选择非常有限或没有治疗选择的心力衰竭患者，心脏基因治疗在心力衰竭治疗中具有巨大的前景。腺相关病毒（AAV）基因载体的引入改变了心脏基因治疗的模式，现在它是临床和临床前研究中慢性心力衰竭基因治疗的主要选择载体。最近，以AAV-1介导的肌浆网Ca2+ ATP酶（SERCA2a）基因治疗针对慢性晚期心力衰竭患者为先导，该领域在临床转化方面取得了重大进展。与此同时，几个独立实验室报告了在临床上相关的心力衰竭大型动物模型中成功的基因治疗方法，其中一些方法预计将在不久的将来进入临床试验。本综述将重点关注正在进行临床试验以及接近首次临床试验应用的针对心力衰竭的基因治疗方法。
