Daadi Marcel M, Pivirotto Phillip, Bringas John, Cunningham Janet, Forsayeth John, Eberling Jamie, Bankiewicz Krys S
Department of Neurosurgery, Stanford University, Stanford, USA.
Neuroreport. 2006 Feb 6;17(2):201-4. doi: 10.1097/01.wnr.0000198952.38563.05.
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.
本报告首次描述了在帕金森病非人灵长类动物模型中，重组腺相关病毒2型（AAV2）人芳香族L-氨基酸脱羧酶（hAADC）基因转移在3年存活期后的稳定性。用浓度为2×10¹²vg/ml的AAV2-hAADC以30微升/部位的剂量对1-甲基-4-苯基-1,2,3,6-四氢吡啶损伤的猴子进行六次注射，注射部位为尾状核和壳核。立体学分析显示，在基因转移存活时间8周和3年后，纹状体中AAV2-hAADC转导细胞的总数增加了46.6%。在8周龄的动物中，AADC⁺细胞的分布分散且不均匀，而在3岁的动物中，其分布广泛且均匀。共聚焦分析表明，约85%的AADC⁺细胞为神经元核免疫反应性细胞。
