NGF GENE THERAPY IN PRIMATE MODELS OF AGING

中性粒细胞因子是一种潜在的候选治疗 神经退行性疾病，如阿尔茨海默病。 关键一步 为了促进营养因子的临床应用， 长期将这些大分子递送到CNS的策略 一段时间。 基因治疗是一种很有前途的方法， 这个任务。 建议的工作旨在扩大我们的知识 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。 具体而言，现有 基因治疗方法和已建立的测定将用于 评价i）在灵长类动物CNS内递送的NGF的分布 通过基因治疗技术，ii）异位递送的NGF的影响 在未损伤的基底前脑胆碱能神经元中， 年轻的成年动物（就细胞性能和正常靶细胞而言 神经支配），和iii）基底神经元反应的年龄相关变化 前脑胆碱能神经元对基因传递的NGF作用的影响 治疗方法（特别是关于外源性NGF的影响） 将具有正常的目标神经支配）。

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).