Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy

TO-2 strain hamsters with dilated cardiomyopathy, gene deletion of delta -sarcoglycan (SG) and no expression of alpha-, beta-, gamma-, and delta -SG; proteins are useful for developing the potential gene therapy of intractable heart failure. We prepared recombinant adeno-associated virus vector including normal delta -SG gene driven by CMV promoter and intramurally administered in vivo. The transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal's life expectancy. Immunostaining demonstrated reexpression of not only delta -SG but also other three SGs in 40% cells in the transfected region and normalization of the diameter of transduced cardiomyocytes. Hemodynamic study revealed preferential amelioration of the diastolic indices (LVEDP, the dP/dt(min) and CVP), These results provide the first evidence that supplementation of a specific gene with efficient and sustained transfection capability restores the genetic, morphological, and functional deteriorations. (C) 2001 Academic Press.