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PMID: 7669103 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Long-term behavioral recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylase.

Science (New York, N.Y.) ·Vol. 266 ·No. 5189 ·1994-11-25 ·Pages 1399-403

During MJ, Naegele JR, O'Malley KL, Geller AI

Abstract

One therapeutic approach to treating Parkinson's disease is to convert endogenous striatal cells into levo-3,4-dihydroxyphenylalanine (L-dopa)-producing cells. A defective herpes simplex virus type 1 vector expressing human tyrosine hydroxylase was delivered into the partially denervated striatum of 6-hydroxydopamine-lesioned rats, used as a model of Parkinson's disease. Efficient behavioral and biochemical recovery was maintained for 1 year after gene transfer. Biochemical recovery included increases in both striatal tyrosine hydroxylase enzyme activity and in extracellular dopamine concentrations. Persistence of human tyrosine hydroxylase was revealed by expression of RNA and immunoreactivity.

MeSH Terms
Animals Base Sequence Corpus Striatum/enzymology,metabolism Denervation Disease Models, Animal Dopamine/metabolism Gene Transfer Techniques Genetic Therapy Genetic Vectors Humans Levodopa/metabolism Male Molecular Sequence Data Motor Activity Neurons/enzymology Parkinson Disease/metabolism,therapy Rats Rats, Sprague-Dawley Simplexvirus/genetics Tyrosine 3-Monooxygenase/genetics,metabolism
Chemicals
Levodopa Tyrosine 3-Monooxygenase Dopamine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
During M J
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510.
Naegele J R
O'Malley K L
Geller A I
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
0036-8075
DOI
10.1126/science.266.5189.1399
Published
1994-11-25
Pages
1399-403
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2638002
Subset
IM
Grants
NEI NIH HHS · EY09749 · United States
NINDS NIH HHS · NS06208 · United States
NINDS NIH HHS · NS28227 · United States
Corrections
CommentIn
PMID: 7638605
External Links
PubMed source DOI: 10.1126/science.266.5189.1399 PMC Full Text View journal details
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