title: Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer.
abstract: An inherited deficiency of beta-glucuronidase in humans, mice and dogs causes mucopolysaccharidosis VII (Sly syndrome), a progressive degenerative disease that reduces lifespan (to an average of 5 months in mice) and results from lysosomal storage of undegraded glycosaminoglycans in the spleen, liver, kidney, cornea, brain and skeletal system. Bone marrow transplantation in mutant mice provides a source of normal enzyme ('cross-correction'), which substantially improves the clinical condition and extends the average lifespan to 18 months. Gene therapy by transfer of a beta-glucuronidase gene into mutant haematopoietic stem cells is an alternative approach, but it is not known whether the low expression of vector-transferred genes in vivo would be sufficiently effective. Here we show that retroviral vector-mediated transfer of the gene to mutant stem cells results in long-term expression of low levels of beta-glucuronidase which partially corrects the disease by reducing lysosomal storage in liver and spleen.
authors: Jackson Laboratory, Bar Harbor, Maine 04609.
authors: J H
authors: JH
authors: Wolfe
authors: M S
authors: MS
authors: Sands
authors: J E
authors: JE
authors: Barker
authors: B
authors: B
authors: Gwynn
authors: L B
authors: LB
authors: Rowe
authors: C A
authors: CA
authors: Vogler
authors: E H
authors: EH
authors: Birkenmeier
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000201:enzymology; D016026:Bone Marrow Transplantation; D015316:Genetic Therapy; D005822:Genetic Vectors; D005966:Glucuronidase / Q000235:genetics*; D006025:Glycosaminoglycans / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D016538:Mucopolysaccharidosis VII / Q000628:therapy*; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000201:enzymology / Q000637:transplantation / Q000648:ultrastructure; D014162:Transfection
chemical_list: D006025:Glycosaminoglycans; D005966:Glucuronidase