Long-term behavioral recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylase.
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.
During
M J
MJ
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510.
Naegele
J R
JR
O'Malley
K L
KL
Geller
A I
AI
D000818:Animals; D001483:Base Sequence; D003342:Corpus Striatum / Q000201:enzymology* / Q000378:metabolism; D003714:Denervation; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009043:Motor Activity; D009474:Neurons / Q000201:enzymology; D010300:Parkinson Disease / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine