MARMOSET MODEL FOR PARKINSON'S DISEASE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在现有的RO 1资助的支持下，我们在帕金森病（PD）小鼠模型中表明，造血干细胞（HSC）衍生的巨噬细胞介导的胶质细胞系衍生的神经营养因子（GDNF）的递送对保护多巴胺神经元非常有效，多巴胺神经元是PD中受影响的主要细胞类型。GDNF的神经保护作用已被广泛接受，但如何将其输送到大脑仍存在问题。由于血脑屏障，全身递送是无效的，而直接CNS递送是具有挑战性的。我们通过巨噬细胞递送GDNF的方法是创新的。在我们将其应用于临床之前，我们需要在非人类灵长类动物中证实基于HSC的巨噬细胞递送GDNF的神经保护和恢复作用。我们选择绒猴有几个原因：1）我们在当地有资源（SNPRC）; 2）绒猴已被建立为MPTP治疗的PD模型; 3）许多其他优势，包括它们的小尺寸。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Supported by an existing RO1 grant, we showed in a mouse model of Parkinson's disease (PD) that hematopoietic stem cell (HSC)-derived macrophage mediated delivery of glial cell line-derived neurotrophic factor (GDNF) is very effective to protect dopamine neurons, which are the major cell type affected in PD. The neuroprotective effect of GDNF is well accepted but how to deliver it to the brain is problematic. Systemic delivery is ineffective due to the blood-brain barrier, while direct CNS delivery is challenging. Our approach to deliver GDNF by macrophages is innovative. Before we move this to the clinic, we need to confirm the neuroprotective and restorative effect of HSC-based macrophage delivery of GDNF in a non-human primate. We choose marmoset for a few reasons: 1) we have the resource (SNPRC) locally; 2) marmosets have been established as PD models with MPTP treatment; and 3) many other advantages including their small size.