NEURAL AND PARANEURAL GRAFTS IN PARKINSONIANS

在过去的十年里，神经移植已经被证明 有效改善啮齿动物模型神经功能缺失 帕金森氏症，亨廷顿氏症的系统， 神经内分泌紊乱和认知缺陷。这一成功之处 啮齿类动物的移植使人们认为神经移植 可能在治疗人类神经疾病方面有治疗价值 包括帕金森氏症在内的疾病。该计划的目的是 目前的方案项目是解决临床前问题，其中 必须加以解决才能发展出合理的临床方法 使用神经移植治疗帕金森症。 我们的研究始于这样一个前提，即实际的捐赠者来源 如果临床试验要继续进行，就必须确定组织。项目 1关注潜在的非胎儿细胞的体外特性。 供体组织包括细胞系，可能用于 移植。这个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，可用于 植入。项目2进行体内分析 项目1中利用啮齿动物确定的潜在供体组织 帕金森氏症的模型系统。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 将集中在副神经组织上，并将进行 两个项目1和2的相关超微结构研究。 项目4将评估MPTP诱导的发展 非人灵长类帕金森病及其治疗效果 在扭转功能缺陷方面的移植。核心A是 将负责的实验动物医疗设施 这些研究中使用的所有非人类灵长类动物。总的来说，这些 项目代表了对潜在捐赠者的系统调查 可用于临床的新生儿来源的组织 帕金森氏症的治疗。这些研究的结果 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.