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. 1989 Nov;86(22):9011–9014. doi: 10.1073/pnas.86.22.9011

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

J A Wolff 1, L J Fisher 1, L Xu 1, H A Jinnah 1, P J Langlais 1, P M Iuvone 1, K L O'Malley 1, M B Rosenberg 1, S Shimohama 1, T Friedmann 1, et al.
PMCID: PMC298422  PMID: 2573072

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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