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Titolo:
Functional effect of adeno-associated virus mediated gene transfer of aromatic L-amino acid decarboxylase into the striatum of 6-OHDA-lesioned rats
Autore:
Sanchez-Pernaute, R; Harvey-White, J; Cunningham, J; Bankiewicz, KS;
Indirizzi:
NINCDS, Mol Therapeut Sect, NIH, Bethesda, MD 20892 USA NINCDS Bethesda MD USA 20892 Therapeut Sect, NIH, Bethesda, MD 20892 USA Avigen Inc, Alameda, CA 94502 USA Avigen Inc Alameda CA USA 94502Avigen Inc, Alameda, CA 94502 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 4, anno: 2001,
pagine: 324 - 330
SICI:
1525-0016(200110)4:4<324:FEOAVM>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXPRESSING TYROSINE-HYDROXYLASE; GTP-CYCLOHYDROLASE-I; PARKINSONS-DISEASE; L-DOPA; PRIMARY FIBROBLASTS; 6-HYDROXYDOPAMINE-TREATED RATS; EXTRACELLULAR DOPAMINE; BEHAVIORAL RECOVERY; AAV VECTOR; BRAIN;
Keywords:
L-DOPA; Parkinson's disease; AAV; rat model; AADC; gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Bankiewicz, KS Univ Calif San Francisco, Dept Neurosurg, Mission Ctr Bldg,Room 230,1855 Folsom St, San Francisco, CA 94103 USA Univ Calif San Francisco Mission Ctr Bldg,Room 230,1855 Folsom St San Francisco CA USA 94103
Citazione:
R. Sanchez-Pernaute et al., "Functional effect of adeno-associated virus mediated gene transfer of aromatic L-amino acid decarboxylase into the striatum of 6-OHDA-lesioned rats", MOL THER, 4(4), 2001, pp. 324-330

Abstract

In animal models of Parkinson's disease, gene transfer of aromatic L-aminoacid decarboxylase (AADC) leads to an increase in the capacity of the striatum to decarboxylate exogenous L-DOPA. However, the functional effects of enhanced L-DOPA to dopamine conversion have not been explored. Here, we show that following adeno-associated virus (AAV)-AADC transduction, the transgenic AADC is able to decarboxylate exogenous L-DOPA more efficiently so that a dose of L-DOPA ineffective before gene transfer elicits a motor asymmetry (rotational behavior) following gene transfer. Furthermore, rotation scores showed a strong correlation with AADC activity in the lesioned striatum, thus allowing for behavioral screening of successful gene transfer in thebrain. In animals receiving AAV2-AADC, dopamine production was restored to50% of normal levels 12 weeks after the infusion. Microdialysis experiments demonstrated an in vivo enhanced conversion of L-DOPA to dopamine, but nostorage capacity as dopamine was released to the extracellular space in a continuous, nonregulated fashion. In addition to the potential clinical benefit of improving decarboxylation efficiency in Parkinson's disease, our approach may be relevant for the treatment of AADC deficiency, a rare, autosomal recessive disorder causing a severe movement disorder and progressive cognitive impairment.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 14:54:48