Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys.
2006
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. I-Methyl-4-phenyl-I,2,3,6-tetrahydropyridine-lesioned monkeys were treated with six injections of 30 μl/site of AAV2-hAADC at a concentration of 2 x I0 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.
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