Gene therapy of advanced heart failure

基因治疗晚期心力衰竭的疗效应根据体内心肌收缩能力和实验动物的预后来检验。我们制备了正常的δ-SG基因或报告基因(Lac Z)，由相同的巨细胞病毒启动子驱动，并在开胸手术中肌肉注射给DCM仓鼠(To-2株)。在一项初步研究中，我们检查了这些动物在心肌变性开始之前的适当年龄(Kawada等人，B.B.R.C.，2001)。正常仓鼠的寿命为100周，而To-2品系仓鼠的寿命可达30周(Sole，Hamster Information Service1986)。在TO-2动物中，单独使用Lac Z的动物在4周大时死亡，并急剧下降到160天左右死亡。这些时间段与之前报道的数据相符。相反，另一组共转染δ-SG和Lac Z的小鼠没有死亡，并一直活跃到250日龄。超声心动图证实改善的LVDS、%FS、LVEF，但不能证实LVDd。因此，这是第一个通过基因治疗挽救晚期失败的严重预后的报告(Kawada等人，Proc.Natl。阿卡德。SCI。美国，2002年)。

The efficacy of gene therapy of advanced heart failure should be examined by the in vivo contractility of cardiac muscle and the prognosis of the experimental animals. We prepared normal δ-SG gene or reporter gene (Lac Z), driven by the same CMV promoter and administered intramuscularly to DCM hamster hearts (TO-2 strain) under open-chest surgery. In a preliminary study, we examined the appropriate age of the animals just before the onset of myocardial degeneration (Kawada et al., B.B.R.C., 2001).The life-span of normal hamsters is 100week, and TO-2 strain hamsters survive up to 30 weeks (Sole, Hamster Information Srvice 1986). In TO-2 animals, the group administered Lac Z alone strated to die from 4 weeks old and sharply declined to die around 160 days. These periods matched to the data reported previously. In contrast, another group cotransfected δ-SG and Lac Z did not die and remained active to 250 day old. The echocardiography confirmed the improved LVDs, %FS, LVEF but not LVDd. Thus this is the first report that the grave prognosis of advanced failure was rescued by the gene therapy (Kawada et al., Proc.Natl. Acad. Sci. USA, 2002).