title: Long-term expression of beta-glucuronidase by genetically modified human neural progenitor cells grafted into the mouse central nervous system.
abstract: Mucopolysaccharidosis type VII (MPS VII) is an inherited disease caused by beta-glucuronidase (beta-glu) deficiency. This deficiency results in the lysosomal accumulation of glycosaminoglycans in all tissues and affects a wide range of organs, including the central nervous system (CNS). Gene transfer is a promising approach to therapy for MPS VII because it allows extensive delivery of the enzyme to the affected tissues. We studied neurotransplantation of primary human cells to supply beta-glucuronidase to the CNS. Human neural progenitor cells (HNPC) were amplified and cotransduced with two lentiviral vectors, one encoding the green fluorescent protein and the other the human beta-glu. We show that these cells strongly expressed both transgenes in culture. When grafted into the mouse striatum, HNPC differentiated into neurons and astrocytes and expressed the two transgenes for at least 6 months. This study therefore paves the way for the treatment of MPS VII by long-term delivery of the appropriate enzyme.
authors.affiliation: Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Bat. CERVI, Hôpital de la Pitié-Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Buchet
authors.forename: Ché
authors.initials: C
authors.lastname: Serguera
authors.forename: Véronique
authors.initials: V
authors.lastname: Zennou
authors.forename: Pierre
authors.initials: P
authors.lastname: Charneau
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
mesh_terms: D000367:Age Factors; D000818:Animals; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000601:surgery; D005260:Female; D016332:Fetal Tissue Transplantation; D015870:Gene Expression; D015316:Genetic Therapy; D005966:Glucuronidase / Q000235:genetics*; D049452:Green Fluorescent Proteins; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D016538:Mucopolysaccharidosis VII / Q000628:therapy*; D009474:Neurons / Q000502:physiology / Q000637:transplantation*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D019076:Transgenes / Q000235:genetics
chemical_list: D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D005966:Glucuronidase