title: Retroviral-mediated transfer of the galactocerebrosidase gene in neural progenitor cells.
abstract: Globoid cell leukodystrophy (GCL or Krabbe disease) is a recessive disease caused by mutations of the lysosomal enzyme galactocerebrosidase (GALC) and twitcher is the murine model of GCL. We have prepared retroviral packaging cell lines to transduce the GALC gene. Retroviral transduction restored GALC activity in GCL fibroblasts and increased such activity to very high levels in immortalized neural progenitor cells (ST14A cells). GALC activity was also normalized in twitcher fibroblasts co-cultured with ST14A cells over-expressing GALC, demonstrating that this enzyme is secreted and can be imported efficiently by GALC-deficient cells. These results give the necessary background to evaluate the therapeutic effect in twitcher of brain grafting of neural progenitor cells engineered to release high levels of GALC.
authors.affiliation: Department of Biochemistry and Genetics, Istituto Nazionale Neurologico Carlo Besta, Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Torchiana
authors.forename: L
authors.initials: L
authors.lastname: Lulli
authors.forename: E
authors.initials: E
authors.lastname: Cattaneo
authors.forename: F
authors.initials: F
authors.lastname: Invernizzi
authors.forename: R
authors.initials: R
authors.lastname: Orefice
authors.forename: B
authors.initials: B
authors.lastname: Bertagnolio
authors.forename: S
authors.initials: S
authors.lastname: Di Donato
authors.forename: G
authors.initials: G
authors.lastname: Finocchiaro
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002490:Central Nervous System / Q000166:cytology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000502:physiology; D005698:Galactosylceramidase / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000628:therapy*; D051379:Mice; D012190:Retroviridae / Q000235:genetics*; D013234:Stem Cells / Q000502:physiology
chemical_list: D005698:Galactosylceramidase