SHIN Wee soo University Tokyo, Health Service Center, Research Associate, 保健管理センター, 助手 (10211971)
SUZUKI Jun-ichi University Tokyo, Health Service Center, Assistant Professor, 保健管理センター, 講師 (50260485)
UEHARA Yoshio University Tokyo, Health Service Center, Associate Professor, 保健管理センター, 助教授 (40184965)
KAWADA Tomie Niigata University, Hospital Division of Pharmacy, Associate Professor, 病院, 薬剤部・現助教授 (00186107)
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).