Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys.
The present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (AAV2) human aromatic L-amino acid decarboxylase (hAADC) gene transfer after 3-year survival time in a non-human primate model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys were treated with six injections of 30 microl/site of AAV2-hAADC at a concentration of 2 x 10(12) vg/ml into the caudate and putamen. Stereological analysis revealed a 46.6% increase in the total number of AAV2-hAADC-transduced cells in the striatum between 8 weeks and 3 years after gene transfer survival time. In the 8-week animals, the distribution of the AADC+ cells was dispersed and heterogeneous, whereas in the 3-year animals it was widespread and homogenous. Confocal analysis demonstrated that approximately 85% of the AADC+ cells were neuronal nuclei immunoreactive.
Daadi
Marcel M
MM
Department of Neurosurgery, Stanford University, Stanford, USA. mdaadi@parkinsonsinstitute.org
Pivirotto
Phillip
P
Bringas
John
J
Cunningham
Janet
J
Forsayeth
John
J
Eberling
Jamie
J
Bankiewicz
Krys S
KS
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D002421:Caudate Nucleus / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count / Q000379:methods; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000473:pathology* / Q000628:therapy; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods*
D001142:Aromatic-L-Amino-Acid Decarboxylases; D010751:Phosphopyruvate Hydratase