title: [Somatic gene therapy of dilated cardiomyopathy].
abstract: 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 delta-sarcoglycan (SG), loss of all four SGs, alpha-, beta-, gamma- and delta-SG proteins, and are useful for developing gene therapy of the hereditary DCM. The delta-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 delta-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 delta-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 delta-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.
authors.affiliation: Division of Pharmacy, Niigata University Medical Hospital, Japan. tomie@med.niigata-u.ac.jp
authors.forename: Tomie
authors.initials: T
authors.lastname: Kawada
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Toyo-Oka
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000628:therapy*; D006224:Cricetinae; D000229:Dependovirus; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051381:Rats