A Neuroprotective Vaccine for Parkinson's Disease

描述（由申请人提供）：许多不同的治疗方法可以暂时改善帕金森病（PD）的症状。然而，这些治疗方法都不能减缓多巴胺能神经元的逐渐丧失。长期以来，人们一直认为免疫细胞浸润到损伤区域或中枢神经系统的神经变性只会产生有害的后果。然而，对野生型和免疫缺陷小鼠的研究发现，免疫缺陷小鼠的神经修复反应降低。此外，越来越多的研究表明，在几种不同的神经损伤和神经退行性变动物模型中，接种髓鞘碱性蛋白（MBP）或Copaxone可以诱导抑制神经元退行性变的免疫反应。我们已经开始评估大脑免疫功能的调节是否可能代表在MPTP小鼠模式下保存多巴胺能神经元的一种新的治疗策略；PD。我们的初步研究发现，与未接种mptp的小鼠相比，接种MBP导致mptp治疗小鼠纹状体多巴胺水平高出70%。本研究的目的是评估影响疫苗效力的因素，并表征疫苗诱导的免疫反应对mptp处理小鼠多巴胺能神经元的影响。我们还将评估科帕松治疗是否对mptp诱导的神经毒性具有神经保护作用。科帕松是FDA批准的人类用药。该提案的结果将为免疫反应如何影响多巴胺能神经元提供基本信息，并可能导致减缓人类PD进展的新方法。

DESCRIPTION (provided by applicant): A number of different treatments can temporarily ameliorate the symptoms due to Parkinson's disease (PD). However, none of these treatments can slow the progressive loss of dopaminergic neurons. It has been long thought that immune cell infiltration into the areas of injury or neurodegeneration in the central nervous system had only deleterious consequences. However, studies with wildtype and immunodeficient mice have found that neurorepair responses are reduced in immune-deficient mice. Moreover, an expanding number of studies have shown that vaccination with myelin basic protein (MBP) or Copaxone can induce immune responses that inhibit neuronal degeneration in several different animal models of neuronal injury and neurodegeneration. We have begun to evaluate whether modulation of immune function in the brain may represent a novel treatment strategy for preserving dopaminergic neurons in the MPTP mouse mode; of PD. Our preliminary studies have found that vaccination with MBP leads to 70% higher levels of striatal dopamine in MPTP-treated mice compared to unvaccinated MPTP-treated mice. The goal of this proposal is to evaluate the factors affecting vaccine efficacy and to characterize the impact of vaccine-induced immune responses on dopaminergic neurons in MPTP-treated mice. We will also evaluate whether Copaxone treatment is neuroprotective against MPTP-induced neurotoxicity. Copaxone is an FDA approved substance for human use. The results of the proposal will provide basic information on how immune responses can affect dopaminergic neurons and may lead to novel approaches to slow the progression of human PD.