NEURAL AND PARANEURAL GRAFTS IN PARKINSONIANS

在过去的十年里，神经移植已经被证明可以 有效改善啮齿动物模型中的神经缺陷 帕金森氏症，亨廷顿氏症， 神经内分泌失调和认知缺陷。 这一成功与 在啮齿动物身上的移植实验表明， 可能对治疗人类神经系统疾病 包括帕金森氏症在内的疾病。 的目的 目前的计划项目是解决临床前问题， 必须解决，以制定合理的临床方法 用神经移植治疗帕金森症 我们的研究开始的前提是， 如果要进行临床试验，就必须识别组织。 项目 1侧重于体外表征潜在的非胎儿 包括细胞系的供体组织，其可用于 移植 该项目的一个重要组成部分是 创造多巴胺能神经元的细胞杂交体， 置入 项目2进行体内分析， 在项目1中使用啮齿动物确定的预期供体组织 帕金森症的模型系统。 项目3还致力于 啮齿动物模型系统中供体组织的体内分析， 将集中于神经旁组织， 项目1和项目2的相关超微结构研究。 项目4将评估MPTP的发展， 非人灵长类的帕金森综合征和 移植逆转功能缺陷。 核心A是 实验动物医疗机构将负责 这些研究中使用的所有非人类灵长类动物。 统称 项目代表了对潜在捐助者的系统调查 来自胎儿来源的组织，其可用于临床， 帕金森病的治疗方法 结果从这些 研究应提供必要的临床前数据， 继续进行临床研究。

In the past decade neural transplants have been demonstrated to be effective in ameliorating neurological deficits in rodent model systems of Parkinson's disease, Huntington's disease, neuroendocrine disorders and cognitive deficits. This success with transplants in rodents has led to suggestions that neural grafts might be of therapeutic value in treating human neurological disorders including Parkinson's disease. The purpose of the present program project is to address the pre-clinical issue which must be resolved in order to develop a rational clinical approach for using neural transplants to treat Parkinsonism. Our studies begin with the premise that practical sources of donor tissue must be identified if clinical trials are to proceed. Project 1 focuses on the characterization in vitro of potential nonfetal donor tissues including cell lines which might be used for transplantation . An important component of this project is to create cell hybrids of dopaminergic neurons which can be used for implantation. Project 2 conducts the in vivo analysis of the prospective donor tissues identified in Project 1 utilizing rodent model systems of Parkinsonism. Project 3 is also committed to the in vivo analysis of donor tissues in rodent model systems but will concentrate on paraneural tissues and will conduct correlative ultrastructural studies for both Projects 1 and 2. Project 4 will assess the development of MPTP induced Parkinsonism in nonhuman primates and the efficacy of transplants in reversing the functional deficits. Core A is the Laboratory Animal Medical Facility which will be responsible for all nonhuman primates used in these studies. Collectively these projects represent a systematic investigation of potential donor tissues from neonfetal sources which can be utilized clinically for the treatment of Parkinson's disease. The results from these studies should provide the necessary pre-clinical data needed to proceed with clinical investigations.