Gene therapy of advanced heart failure

晚期心力衰竭基因治疗的疗效应通过在体心肌收缩力和实验动物预后来检验。我们制备了正常的δ-SG基因或报告基因（Lac Z），由相同的CMV启动子驱动，并在开胸手术下肌内注射到DCM仓鼠心脏（TO-2株）。在初步研究中，我们检查了心肌变性发作前动物的适当年龄（Kawada等人，B.B.R.C. 2001).正常仓鼠的寿命为100周，TO-2品系仓鼠可存活长达30周（Sole，CIMIS 1986）。在TO-2动物中，单独给予Lac Z的组从4周龄开始死亡，并在160天左右急剧下降至死亡。这些时期与以前报告的数据相符。与此相反，δ-SG和Lac Z共转染的另一组细胞没有死亡，并保持活性至250日龄。超声心动图证实LVDs、%FS、LVEF改善，但LVDd未改善。因此，这是基因治疗挽救晚期衰竭的严重预后的第一篇报道（Kawada et al.，Proc.Natl. Acad. Sci. USA，2002）。

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).