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Science 25 November 1994:
Vol. 266. no. 5189, pp. 1399 - 1403
DOI: 10.1126/science.266.5189.1399
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Articles

Long-Term Behavioral Recovery in Parkinsonian Rats by an HSV Vector Expressing Tyrosine Hydroxylase

Matthew J. During 1, Janice R. Naegele 2, Karen L. O'Malley 3, and Alfred I. Geller 4

1 Departments of Surgery and Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
2 Department of Biology, Wesleyan University, Middletown, CT 06457, USA
3 Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA
4 Division of Endocrinology, Children's Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA

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.

Submitted on July 22, 1994
Accepted on September 20, 1994


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