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

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, 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

Research output: Contribution to journal › Article › peer-review

231 Scopus citations

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 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 language	English
Pages (from-to)	9011-9014
Number of pages	4
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	86
Issue number	22
DOIs	https://doi.org/10.1073/pnas.86.22.9011
State	Published - 1989

Keywords

6-hydroxydopamine transplantation
retroviral vector
tyrosine hydroxylase

Access to Document

10.1073/pnas.86.22.9011

Cite this

Wolff, J. A., Fisher, L. J., Xu, L., Jinnah, H. A., Langlais, P. J., Iuvone, P. M., O'Malley, K. L., Rosenberg, M. B., Shimohama, S., Friedmann, T., & Gage, F. H. (1989). Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease. Proceedings of the National Academy of Sciences of the United States of America, 86(22), 9011-9014. https://doi.org/10.1073/pnas.86.22.9011

@article{7ae1a6bac09a4be9838b6e30c35c61a8,

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 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.",

keywords = "6-hydroxydopamine transplantation, retroviral vector, tyrosine hydroxylase",

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

year = "1989",

doi = "10.1073/pnas.86.22.9011",

language = "English",

volume = "86",

pages = "9011--9014",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

number = "22",

}

Wolff, JA, Fisher, LJ, Xu, L, Jinnah, HA, Langlais, PJ, Iuvone, PM, O'Malley, KL, Rosenberg, MB, Shimohama, S, Friedmann, T & Gage, FH 1989, 'Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease', Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 22, pp. 9011-9014. https://doi.org/10.1073/pnas.86.22.9011

TY - JOUR

T1 - Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease

AU - Wolff, J. A.

AU - Fisher, L. J.

AU - Xu, L.

AU - Jinnah, H. A.

AU - Langlais, P. J.

AU - Iuvone, P. M.

AU - O'Malley, K. L.

AU - Rosenberg, M. B.

AU - Shimohama, S.

AU - Friedmann, T.

AU - Gage, F. H.

PY - 1989

Y1 - 1989

N2 - 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 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.

AB - 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 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.

KW - 6-hydroxydopamine transplantation

KW - retroviral vector

KW - tyrosine hydroxylase

UR - http://www.scopus.com/inward/record.url?scp=0024326943&partnerID=8YFLogxK

U2 - 10.1073/pnas.86.22.9011

DO - 10.1073/pnas.86.22.9011

M3 - Article

C2 - 2573072

AN - SCOPUS:0024326943

SN - 0027-8424

VL - 86

SP - 9011

EP - 9014

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 22

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this