title: Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease.
abstract: Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase [TH; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2]. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell culture medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurological disease and specific implications for Parkinson disease.
authors.affiliation: Department of Pediatrics, University of California School of Medicine, La Jolla 92093.
authors.forename: J A
authors.initials: JA
authors.lastname: Wolff
authors.forename: L J
authors.initials: LJ
authors.lastname: Fisher
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: H A
authors.initials: HA
authors.lastname: Jinnah
authors.forename: P J
authors.initials: PJ
authors.lastname: Langlais
authors.forename: P M
authors.initials: PM
authors.lastname: Iuvone
authors.forename: K L
authors.initials: KL
authors.lastname: O'Malley
authors.forename: M B
authors.initials: MB
authors.lastname: Rosenberg
authors.forename: S
authors.initials: S
authors.lastname: Shimohama
authors.forename: T
authors.initials: T
authors.lastname: Friedmann
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000201:enzymology / Q000637:transplantation; D005822:Genetic Vectors; D007980:Levodopa / Q000378:metabolism*; D008979:Moloney murine leukemia virus / Q000235:genetics*; D010300:Parkinson Disease / Q000201:enzymology / Q000601:surgery*; D010957:Plasmids; D051381:Rats; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
chemical_list: D007980:Levodopa; D004247:DNA; D014446:Tyrosine 3-Monooxygenase