Research from National Institutes of Health reveals new findings on gene therapy
2008 JAN 17 -- "Fabry disease is an inborn error of glycosphingolipid catabolism resulting from a deficiency of lysosomal enzyme a-galactosidase A. The major clinical manifestations of the disease, such as stroke, cardiac dysfunction, and renal impairment, are thought to be caused by vasculopathy due to progressive accumulation of globotriaosylceramide in vascular endothelial cells. The pathogenesis of the vasculopathy has not been elucidated," scientists in the United States report. "Since in vitro studies using primary endothelial cells are hampered by the limited lifespan of these cells, the availability of cultured endothelial cells with an extended lifespan is critical for the study of the vasculopathy of Fabry disease. We therefore generated an endothelial cell line from a Fabry hemizygote by introduction of human telomerase reverse transcriptase gene. The cell line has markedly extended lifespan compared to parental primary cells. The cells stably express many key markers of endothelial cells such as von Willebrand factor, CD31, CD34, and endothelial nitric oxide synthase (eNOS) and retain functional characteristics such as uptake of acetylated low-density lipoprotein, responsiveness to angiogenic growth factors, up-regulation of eNOS production upon extracellular stimuli, and formation of tube-like structures on Matrigel basement membrane matrix. The cells show significantly reduced activity of a-galactosidase A compared with primary endothelial cells from normal individuals and accumulate globotriaosylceramide in lysosomes. This cell line will provide a useful in vitro model of Fabry disease and will facilitate systematic studies to investigate pathogenic mechanisms and explore new therapeutic approaches for Fabry disease," wrote J.S. Shen and colleagues, National Institutes of Health. The researchers concluded: "Published by Elsevier Inc." Shen and colleagues published their study in Molecular Genetics and Metabolism (Establishment and characterization of Fabry disease endothelial cells with an extended lifespan. Molecular Genetics and Metabolism, 2007;92(1-2):137-144). For additional information, contact C.R. Kaneski, National Institutes of Health, National Institute Neurology Disorders & Stroke, Development & Metab Neurology Branch, Bldg 10, Rm 3 D04, 9000 Rockville Pike, Bethesda, MD 20892, USA. The publisher's contact information for the journal Molecular Genetics and Metabolism is: Academic Press Inc. Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495, USA. Keywords: United States, Bethesda, Biotechnology, Cardiology, Enzyme Research, Enzymes, Enzymology, Fabry Disease, Galactosidase, Gene Therapy, Genetics, Kidney, Metabolism, Nephrology, Neurology, Proteins, Proteomics, Reverse Transcriptase, Telomerase, Transcriptase, National Institutes of Health. This article was prepared by Gene Therapy Weekly editors from staff and other reports. Copyright 2008, Gene Therapy Weekly via NewsRx.com.
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