Investigators at University of Heidelberg have published new data on gene therapy
2009 JUL 9 - (NewsRx.com) -- "delta-Sarcoglycan is a member of the dystrophin-associated glycoprotein complex linking the cytoskeleton to the extracellular matrix. Similar to patients with defects in the gene encoding delta-sarcoglycan (Sgcd), knockout mice develop cardiomyopathy and muscular dystrophy," researchers in Heidelberg, Germany report. "The aim of our study was to develop an approach for preventing cardiomyopathy in Sgcd-deficient mice by cardiac expression of the intact cDNA upon systemic delivery of adeno-associated viral (AAV) vectors. We packaged the Sgcd cDNA under transcriptional control of a myosin light chain-promoter fused with a cytomegalovirus enhancer into AAV-9 capsids. Vectors carrying either the Sgcd cDNA or an enhanced green fluorescent protein (EGFP) reporter gene were intravenously injected into adult Sgcd knockout mice. After 6 months, immunohistochemistry revealed almost complete reconstitution of the sarcoglycan subcomplex in heart but not skeletal muscle of mice with the Sgcd vector. Furthermore, Sgcd gene transfer resulted in prevention of cardiac fibrosis and significantly increased running distance measured by voluntary wheel running. Left ventricular function remained stable in mice expressing Sgcd while it deteriorated in EGFP controls within 6 months, paralleled by increased expression of brain natriuretic peptide, a molecular marker of heart failure," wrote C. Goehringer and colleagues, University of Heidelberg. The researchers concluded: "Our study establishes an approach to specifically treat hereditary cardiomyopathies by targeting gene expression into the myocardium upon systemic application of AAV vectors.." Goehringer and colleagues published their study in Cardiovascular Research (Prevention of cardiomyopathy in delta-sarcoglycan knockout mice after systemic transfer of targeted adeno-associated viral vectors. Cardiovascular Research, 2009;82(3):404-410). For additional information, contact O.J. Muller, University of Heidelberg, Neuenheimer Feld 410, D-69120 Heidelberg, Germany. Publisher contact information for the journal Cardiovascular Research is: Oxford University Press, Great Clarendon St., Oxford OX2 6DP, England. Keywords: Germany, Heidelberg, Biotechnology, Cardiology, Cardiomyopathies, Cardiomyopathy, Cardiovascular, Cytomegalovirus, Gene Therapy, Genetics, Genomics, Heart Failure, Muscular Dystrophies, Reporter Gene, Treatment, University of Heidelberg. This article was prepared by Gene Therapy Weekly editors from staff and other reports. Copyright 2009, Gene Therapy Weekly via NewsRx.com.
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