1] Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA [2] Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.
Mol Ther. 2013 Dec;21(12):2160-8. doi: 10.1038/mt.2013.180. Epub 2013 Aug 5.
We combined viral vector delivery of human glial-derived neurotrophic factor (GDNF) with the grafting of dopamine (DA) precursor cells from fetal ventral mesencephalon (VM) to determine whether these strategies would improve the anti-Parkinson's effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, an animal model for Parkinson's disease (PD). Both strategies have been reported as individually beneficial in animal models of PD, leading to clinical studies. GDNF delivery has also been reported to augment VM tissue implants, but no combined studies have been done in monkeys. Monkeys were treated with MPTP and placed into four balanced treatment groups receiving only recombinant adeno-associated virus serotype 5 (rAAV5)/hu-GDNF, only fetal DA precursor cells, both together, or a buffered saline solution (control). The combination of fetal precursors with rAAV5/hu-GDNF showed significantly higher striatal DA concentrations compared with the other treatments, but did not lead to greater functional improvement in this study. For the first time under identical conditions in primates, we show that all three treatments lead to improvement compared with control animals.
我们将人胶质源性神经营养因子（GDNF）的病毒载体传递与来自胎鼠腹侧中脑（VM）的多巴胺（DA）前体细胞移植相结合，以确定这些策略是否会改善 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的猴子（帕金森病（PD）的动物模型）中的抗帕金森病效果。这两种策略在 PD 的动物模型中均被报道为单独有益，从而导致了临床研究。GDNF 传递也被报道可以增强 VM 组织植入物，但在猴子中尚未进行联合研究。猴子接受 MPTP 治疗，并分为四个平衡的治疗组，仅接受重组腺相关病毒血清型 5（rAAV5）/ hu-GDNF、仅接受胎鼠 DA 前体细胞、两者同时接受或缓冲盐水溶液（对照）。与其他治疗方法相比，与 rAAV5/hu-GDNF 一起使用胎鼠前体细胞的组合显示出明显更高的纹状体 DA 浓度，但在这项研究中并未导致更大的功能改善。在灵长类动物的相同条件下，我们首次表明，所有三种治疗方法都与对照组动物相比有所改善。
