Sci. Transl. Med.:新基因疗法治疗心脏衰竭

西奈山医学院心血管专家对大动物心脏衰竭模型实施了基因治疗，该疗法的成效显著。相关报道发表在近期的Science Translational Medicine杂志上。该研究检测了SUMO-1基因疗法，该研究是临床前实验的最后阶段。之前基因治疗针对的是SERCA2基因，一期和二期临床效果都很好，而Hajjar 博士在2011年的Nature文章称在人类心衰病人中SUMO-1基因也降低，而SUMO-1调节SERCA2a的活性，即不改变SERCA2a水平的情况下增强蛋白质的功能。之后在小鼠模型中的的研究发现针对SUMO-1基因治疗显著提高心脏功能。

于是本次研究中，科学家检测了分别针对SUMO-1基因，SERCA2基因的基因治疗和两基因结合的疗法的效果。

在大动物心衰模型中，科学家发现单纯转运高剂量的SUMO-1和，同时转运SUMO-1、SERCA2都会增强心脏收缩力，增加血流，减小心脏体积。

Hajjar博士称，该新研究表明SUMO-1对SERCA2的功能实施有重要作用。针对SUMO-1的基因替代疗法将会有效的治疗心衰病人。（转化医学网360zhyx.com）

原文链接：

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SUMO-1 Gene Transfer Improves Cardiac Function in a Large-Animal Model of Heart Failure

Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The amount of myocardial SUMO-1 is decreased in failing hearts, and its knockdown results in severe heart failure (HF) in mice. In a previous study, we showed that SUMO-1 gene transfer substantially improved cardiac function in a murine model of pressure overload–induced HF. Toward clinical translation, we evaluated in this study the effects of SUMO-1 gene transfer in a swine model of ischemic HF. One month after balloon occlusion of the proximal left anterior descending artery followed by reperfusion, the animals were randomized to receive either SUMO-1 at two doses, SERCA2a, or both by adeno-associated vector type 1 (AAV1) gene transfer via antegrade coronary infusion. Control animals received saline infusions. After gene delivery, there was a significant increase in the maximum rate of pressure rise [dP/dt(max)] that was most pronounced in the group that received both SUMO-1 and SERCA2a. The left ventricular ejection fraction (LVEF) improved after high-dose SUMO-1 with or without SERCA2a gene delivery, whereas there was a decline in LVEF in the animals receiving saline. Furthermore, the dilatation of LV volumes was prevented in the treatment groups. SUMO-1 gene transfer therefore improved cardiac function and stabilized LV volumes in a large-animal model of HF. These results support the critical role of SUMO-1 in SERCA2a function and underline the therapeutic potential of SUMO-1 for HF patients.

来源：生物谷  转化医学网