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

Journal Article · Wed Nov 01 00:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.22.9011· OSTI ID:6999247

Wolff, J A; Fisher, L J; Xu, L; Jinnah, H A; Rosenberg, M B; Shimohama, S; Gage, F H ^[1]; Langlais, P J ^[2]; Iuvone, P M ^[3]; O'Malley, K L ^[4]

---

1. Univ. of California School of Medicine, La Jolla (USA)
2. Univ. of California School of Medicine, La Jolla (USA) School of Medicine and Veterans Administration Medical Center, La Jolla (USA) San Diego State Univ., CA (USA)
3. Emory Univ., Atlanta, GA (USA)
4. Washington Univ. School of Medicine, St. Louis, MO (USA)

Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase. 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 cultured 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.

• OSTI ID: 6999247
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:22; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DOPA
BIOSYNTHESIS
NERVE CELLS
GENETIC ENGINEERING
NERVOUS SYSTEM DISEASES
BIOLOGICAL MODELS
CYTOCHEMISTRY
FIBROBLASTS
PLASMIDS
RATS
RECOMBINANT DNA
THERAPY
TYROSINASE
VIRUSES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMISTRY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMISTRY
CONNECTIVE TISSUE CELLS
DISEASES
DNA
DRUGS
ENZYMES
HYDROXY ACIDS
HYDROXYLASES
MAMMALS
MICROORGANISMS
NEUROREGULATORS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PARASITES
RODENTS
SOMATIC CELLS
SYNTHESIS
VERTEBRATES
550401* - Genetics- Tracer Techniques