IGF1 gene transfer into skeletal muscle using recombinant adeno-associated virus in a rat model of liver cirrhosis.
Systemic administration of recombinant IGF1 at low levels has been shown to improve hepatic function, nutritional status and testicular atrophy in rats with CCl4-induced cirrhosis. We have developed a recombinant adeno-associated (rAAV) viral vector containing the cDNA for rat IGF1 and confirmed the expression of IGF1 after intramuscular injection of this vector in a rat model of liver cirrhosis. Although weight of injected muscles was significantly increased in rats with mild cirrhosis, this was not the case in rats with advanced, de-compensated cirrhosis. Furthermore, we found no significant amelioration of liver damage in treated rats at any stage of liver cirrhosis. Our results suggest that IGF1 gene transfer into muscle results in a local effect, at least at the vector dose employed here.
Zaratiegui
M
M
Department of Genetics, University of Navarra, 31008 Pamplona, Spain.
Castilla-Cortázar
I
I
García
M
M
Quiroga
J
J
Prieto
J
J
Novo
F J
FJ
D000818:Animals; D004274:DNA, Recombinant; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008111:Liver Function Tests; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar
D004274:DNA, Recombinant; D007334:Insulin-Like Growth Factor I