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Titolo:
Intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type VII
Autore:
Frisella, WA; OConnor, LH; Vogler, CA; Roberts, M; Walkley, S; Levy, B; Daly, TM; Sands, MS;
Indirizzi:
Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA Washington Univ St Louis MO USA 63110 nternal Med, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA WashingtonUniv St Louis MO USA 63110 pt Psychiat, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA Washington Univ St Louis MO USA 63110 Dept Pathol, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA Washington Univ St Louis MO USA 63110 Dept Genet, St Louis, MO 63110 USA St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63107 USA St Louis UnivSt Louis MO USA 63107 , Dept Pathol, St Louis, MO 63107 USA Mt Sinai Sch Med, Dept Neurobiol, New York, NY USA Mt Sinai Sch Med New York NY USA h Med, Dept Neurobiol, New York, NY USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 3, volume: 3, anno: 2001,
pagine: 351 - 358
SICI:
1525-0016(200103)3:3<351:IIORAV>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; BONE-MARROW TRANSPLANTATION; ENZYME REPLACEMENT THERAPY; LYSOSOMAL STORAGE DISEASE; BETA-GLUCURONIDASE DEFICIENCY; MEDIATED GENE-TRANSFER; ADENOASSOCIATED VIRUS; MOUSE-BRAIN; AAV VECTOR; LONG-TERM;
Keywords:
lysosomal storage diseases; gene therapy; adeno-associated virus; Morris water maze; central nervous system; beta-glucuronidase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Sands, MS Washington Univ, Sch Med, Dept Internal Med, Box 8007,660 S Euclid Ave, StLouis, MO 63110 USA Washington Univ Box 8007,660 S Euclid Ave St Louis MO USA 63110
Citazione:
W.A. Frisella et al., "Intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type VII", MOL THER, 3(3), 2001, pp. 351-358

Abstract

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by the lack of beta -glucuronidase (GUSB) activity. GUSB deficiency leads to the progressive accumulation of undegraded glycosaminoglycans (GAGs)in cells of most tissues, including the brain, and is associated with mental retardation. Reduction of lysosomal storage in the central nervous system and prevention of cognitive dysfunction may require intracranial deliveryof a therapeutic agent during the newborn period that provides a continuous source of GUSB. Therefore, we injected recombinant adeno-associated virusencoding human GUSB into both the anterior cortex and the hippocampus of newborn MPS VII mice. Total GUSB activity in the brain approached normal levels by 18 weeks. Although GUSB activity was concentrated near the injectionsites, lysosomal distension was reduced in most areas of the brain. In addition to histopathologic evidence of GAG reduction, the previously undescribed accumulation of GM2 and GM3 gangliosides in the brain was also prevented. Furthermore, GUSB expression and reduced lysosomal distension correlatedwith improvements in cognitive function as measured in the Morris Water Maze test. These findings indicate that localized overexpression of GUSB has positive effects on the pathology and cognitive function and does not have overt toxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 00:28:04