Glial Progenitor Cells for Treatment of ALS

描述(由申请人提供)：这是一项翻译研究建议，旨在开发神经胶质限制祖细胞(GRP)，作为治疗肌萎缩侧索硬化症(ALS；也称为Lou Gehrig病)的治疗方法。肌萎缩侧索硬化症是一种影响上、下运动神经元的神经退行性疾病。这种疾病的特征是运动神经元的进行性退化和丧失。特定肌肉失去神经刺激会导致萎缩和进行性虚弱，从而导致瘫痪。在大多数接受评估的患者群体中，生存时间为3至5年。目前还没有找到治疗肌萎缩侧索硬化的方法。在肌萎缩侧索硬化症的动物模型中，已经表明GRPS减缓了疾病的进展并改善了呼吸功能。这些实验中使用的动物细胞与人类的剂量不相容。这项建议旨在开发用于ALS治疗的同源人源性GRPs。这项建议的目的是1)证明人的GRPs在ALS动物模型中的行为类似于大鼠GRPs；2)开发用于提纯人GRPs的抗体，使其达到用于细胞治疗生产所需的规格；3)在动物安全研究所需的良好实验室操作(GLP)条件下生产人GRPs；以及4)在动物模型中证明人GRPs是安全、无毒和无致瘤作用的。目标1、4和5将通过将人类GRPs植入相关动物模型的脊髓并在细胞和行为水平上评估其影响来实现。目标2将通过标准抗体生产和纯化方法实现，而目标3将通过标准细胞纯化和根据GLP标准进行的培养技术来实现细胞生产。这些研究的成功完成将成为FDA申请研究性新药(IND)的基础，FDA寻求在ALS进行临床试验。相关性(参见说明)：肌萎缩侧索硬化症(ALS)是一种控制肌肉功能的神经细胞死亡，导致3-5年内死亡的疾病，目前还没有治愈方法。这项提议旨在通过开展开始这一新治疗方法临床试验所需的研究，开发一种治疗这种毁灭性疾病的细胞疗法。如果成功，这项提议将导致一种治疗方法，使受影响的神经细胞恢复正常功能，进而减缓或阻止疾病的发展。

DESCRIPTION (provided by applicant): This is a Translational Research Proposal to develop glial restricted progenitor cells (GRPs) as a therapeutic for the treatment of Amyotropic Lateral Sclerosis (ALS; also known as Lou Gehrig's Disease). ALS is a neurodegenerative disease that affects both upper and lower motor neurons. This disease is characterized by the progressive deterioration and loss of motor neurons.The loss of nerve stimulus to specific muscles results in atrophy and progressive weakness that leads to paralysis. The length of survival in most patient populations that have been evaluated is 3 to 5 years. No cure has yet been found for ALS. In an animal model of ALS it has been shown that GRPs slow disease progression and improve respiratory function. The animal cells used in these experiments are not compatible with human dosing. This proposal aims to develop the homologous human derived GRPs for therapeutic use in ALS. The aims of this proposal are to 1) demonstrate that human GRPs behave similarly to rat GRPs in an animal model of ALS, 2) develop the antibody used to purify human GRPs to the specification required for its use in cellular therapeutic production 3) produce human GRPs under Good Laboratory Practices (GLP) conditions required for animal safety studies and 4) demonstrate that human GRPs are safe, non-toxic, and non-tumorigenicin animal models. Aims 1,4 and 5 will be achieved by implanting human GRPs into the spinal cord of relevant animal models and assessing their effects at both the cellular and behavioral levels. Aim 2 will be achieved by standard antibody production and purification methods, while Aim 3 will entail cellular production by standard cellular purification and culturingtechniques performed according to GLP standards. Successful completion of these studies will form the basis of anInvestigational New Drug (IND) application with the FDA seeking to conduct a clinical trial in ALS. RELEVANCE (See instructions): There is no cure for Amyotrophic Lateral Sclerosis (ALS), a disease in which nerve cells that control muscle function die resulting in death within 3-5 years. This proposal is designed to develop a cellular therapy for the treatment of this devastating disease by performing the studies required to begin a clinical trial of this novel therapeutic approach. If successful, this proposal will lead to a therapy which will restore normal function to the effected nerve cells which in turn will slow or halt the progression of the disease.