Temple University, Translational Medicine/Pharmacology , 3500 N. Broad Street, Philadelphia, 19140 , USA
Expert Opin Biol Ther. 2014 Feb;14(2):183-95. doi: 10.1517/14712598.2014.866085. Epub 2013 Dec 16.
Cardiovascular gene therapy is the third most popular application for gene therapy, representing 8.4% of all gene therapy trials as reported in 2012 estimates. Gene therapy in cardiovascular disease is aiming to treat heart failure from ischemic and non-ischemic causes, peripheral artery disease, venous ulcer, pulmonary hypertension, atherosclerosis and monogenic diseases, such as Fabry disease.
In this review, we will focus on elucidating current molecular targets for the treatment of ventricular dysfunction following myocardial infarction (MI). In particular, we will focus on the treatment of i) the clinical consequences of it, such as heart failure and residual myocardial ischemia and ii) etiological causes of MI (coronary vessels atherosclerosis, bypass venous graft disease, in-stent restenosis).
We summarise the scheme of the review and the molecular targets either already at the gene therapy clinical trial phase or in the pipeline. These targets will be discussed below. Following this, we will focus on what we believe are the 4 prerequisites of success of any gene target therapy: safety, expression, specificity and efficacy (SESE).
心血管基因治疗是基因治疗的第三大热门应用,占 2012 年报告的所有基因治疗试验的 8.4%。心血管疾病中的基因治疗旨在治疗缺血性和非缺血性原因引起的心力衰竭、外周动脉疾病、静脉溃疡、肺动脉高压、动脉粥样硬化和单基因疾病,如法布瑞氏病。
在这篇综述中,我们将重点阐述心肌梗死后心室功能障碍治疗的当前分子靶点。具体来说,我们将重点关注以下方面:i)心肌梗死后的临床后果,如心力衰竭和残余心肌缺血,以及 ii)心肌梗死的病因(冠状动脉血管粥样硬化、旁路静脉移植物疾病、支架内再狭窄)的治疗。
我们总结了综述的方案和分子靶点,这些靶点要么已经处于基因治疗临床试验阶段,要么处于研发阶段。下面将讨论这些靶点。在此之后,我们将重点关注我们认为任何基因治疗靶点成功的 4 个先决条件:安全性、表达、特异性和疗效(SESE)。