Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease

J. A. Wolff, L. J. Fisher, L. Xu, H. A. Jinnah, P. J. Langlais, P. M. Iuvone, K. L. O'Malley, M. B. Rosenberg, S. Shimohama, T. Friedmann, F. H. Gage

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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]. A TH-positive clone was identified by biochemial 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.

Original languageEnglish
Pages (from-to)9011-9014
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number22
StatePublished - 1989


  • 6-hydroxydopamine transplantation
  • retroviral vector
  • tyrosine hydroxylase


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