Abstract
Expression of the rate-limiting enzyme for catecholamine biosynthesis, tyrosine hydroxylase (TH), via retrovital and plasmid expression vectors improved the efficacy of conditionally immortalized nigral neural cells in ameliorating rodent and nonhuman primate models of Parkinson's disease through neural transplantation. No improvement in rotational behavior occurred when sham transplants or nondopaminergic transplants were performed. Transplantation of the temperature-sensitive immortalized parental nigral neural line with a TH expression vector resulted in improvement for at least 2 months. Improvement was accompanied by HPLC evidence of increased l-DOPA production and immunocytochemical evidence of TH in the transfected cells increased over that of the parental line. No tumor formation was detected. These results suggest that: (1) temperature-sensitive immortalized neural cells may be genetically engineered successfully to improve their efficacy for the treatment of parkinsonism; and (2) a change in l-DOPA production, as opposed to growth factor production or other factors, is likely to account for the observed improvement, since the parental and derived lines differ by a single gene.
Original language | English (US) |
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Pages (from-to) | 207-218 |
Number of pages | 12 |
Journal | Experimental Neurology |
Volume | 127 |
Issue number | 2 |
DOIs | |
State | Published - Jun 1994 |
Externally published | Yes |
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience