NGF GENE THERAPY IN PRIMATE MODELS OF AGING

神经营养因子是一种潜在的治疗方案 神经退行性疾病，如阿尔茨海默病。关键的一步 为了推进营养因子的临床应用，将设计 长时间将这些大分子送入中枢神经系统的策略 一段时间。基因治疗是一种很有前途的方法 这项任务。拟议中的工作旨在扩大我们的知识面 关于输送营养因子，特别是NGF的影响， 通过基因治疗技术进入灵长类中枢神经系统。具体地说，现有 基因治疗方法和已建立的检测方法将用于 评估一)神经生长因子在灵长类中枢神经系统内的分布 通过基因治疗技术，II)异位传递的NGF的影响 在未损毁的基底前脑胆碱能神经元上， 幼年成年动物(就细胞性能和正常指标而言 神经支配)，以及iii)与年龄相关的反应的基础 前脑胆碱能神经元对NGF基因递送作用的影响 治疗方法(特别是与外源性NGF的影响有关 会对正常的靶神经有影响)。

Neutrophic factors are a potential candidate for treating neurodegenerative diseases such as Alzheimer's disease. A crucial step for advancing the clinical use of trophic factors will be the design of strategies for delivering these large molecules into the CNS over long periods of time. Gene therapy is a promising approach for accomplishing this task. The proposed work is aimed at expanding our knowledge concerning the impact of delivering trophic factors, particularly NGF, by gene therapy techniques into the primate CNS. Specifically, existing gene therapy approaches and established assays will be used for evaluating i) the distribution of NGF delivered within the primate CNS by gene therapy techniques, ii) the impact of ectopically delivered NGF upon NGF-sensitive basal forebrain cholinergic neurons in the unlesioned, young adult animal (both in terms of cell performance and normal target innervation), and iii) age-related changes in the response of basal forebrain cholinergic neurons to the actions of NGF delivered by gene therapy approaches (especially pertaining to the impact exogenous NGF will have upon normal target innervation).