2002 Volume 119 Issue 1 Pages 37-44
The hereditary form of dilated cardiomyopathy (DCM) accounts for about 20% of human DCM and is a major cause of heart failure. TO-2 strain hamsters show DCM, a gene deletion of δ-sarcoglycan (SG), loss of all four SGs, α-, β-, γ- and δ-SG proteins, and are useful for developing gene therapy of the hereditary DCM. The δ-SG is a component of dystrophin-associated glycoprotein complex that stabilizes sarcolemma. Four familial and sporadic DCM cases have been reported in human patients with the same δ-SG gene mutation. To establish the potential gene therapy of DCM, efficient and long-lasting transduction of the responsible gene is mandatory, especially for improving the functional defect. Recombinant adeno-associated virus (rAAV) vector with δ-SG gene was intramurally transfected to the TO-2 hearts at 5-weeks-old. The transfected myocardium revealed robust expression of both transcript and transgene after 10 and 20 weeks. Immunohistological analyses demonstrated re-expression of not only δ-SG but also the other three SGs and normalization of the diameter of transduced cardiomyocytes without the pathogenicity. Hemodynamic studies revealed preferential amelioration of the diastolic indices. It suggests a novel strategy for the treatment of DCM and the rAAV vector is available for the treatment of several human diseases because of its safety and efficacy.
