MARMOSET MODEL FOR PARKINSON'S DISEASE

帕金森病狨猴模型

• 批准号: 8357709
• 负责人: SENLIN LI
• 金额: $ 0.16万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357709
• 关键词: Affect; Blood - brain barrier anatomy; Brain; Callithrix; Clinic; Disease model; Funding; Grant; Hematopoietic stem cells; Mediating; Modeling; National Center for Research Resources; Parkinson Disease; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; base; cell type; cost; dopaminergic neuron; glial cell-line derived neurotrophic factor; innovation; macrophage; mouse model; nonhuman primate

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在现有的RO1赠款的支持下，我们在帕金森氏病小鼠模型（PD）中表明，造血性干细胞（HSC）衍生的巨噬细胞介导的神经胶质细胞衍生的神经营养因子（GDNF）的传递非常有效，可保护多巴胺神经元，这是PD中的主要细胞类型。 GDNF的神经保护作用已被公认，但是如何将其传递给大脑是有问题的。由于血脑屏障的障碍，全身性传递无效，而直接中枢神经系统的交付则具有挑战性。我们通过巨噬细胞提供GDNF的方法是创新的。在将其移至诊所之前，我们需要确认基于HSC的GDNF在非人类灵长类动物中的神经保护性和恢复性效应。我们选择Marmoset的原因有一些：1）我们本地拥有资源（SNPRC）； 2）MARMOSET已建立为具有MPTP处理的PD模型； 3）许多其他优点，包括它们的尺寸小。