Morphological and physiological restorations of hereditary form of dilatedcardiomyopathy by somatic gene therapy

TO-2 strain hamsters with dilated cardiomyopathy, gene deletion of delta -s arcoglycan (SG) and no expression of alpha-, beta-, gamma-, and delta -SG; proteins are useful for developing the potential gene therapy of intractabl e heart failure. We prepared recombinant adeno-associated virus vector incl uding normal delta -SG gene driven by CMV promoter and intramurally adminis tered in vivo. The transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal's life expectancy. I mmunostaining demonstrated reexpression of not only delta -SG but also othe r three SGs in 40% cells in the transfected region and normalization of the diameter of transduced cardiomyocytes. Hemodynamic study revealed preferen tial amelioration of the diastolic indices (LVEDP, the dP/dt(min) and CVP), These results provide the first evidence that supplementation of a specifi c gene with efficient and sustained transfection capability restores the ge netic, morphological, and functional deteriorations. (C) 2001 Academic Pres s.