Glial Progenitor Cells for Treatment of ALS

描述（由申请人提供）：这是一份开发神经胶质限制性祖细胞（GRPs）作为治疗肌萎缩性侧索硬化症（ALS，也称为Lou Gehrig's Disease）的药物的转化研究申请。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。这种疾病的特点是运动神经元的进行性恶化和丧失。失去对特定肌肉的神经刺激会导致萎缩和进行性无力，最终导致瘫痪。经评估的大多数患者的生存期为3至5年。目前还没有找到治疗ALS的方法。在ALS的动物模型中，已经显示GRPs减缓疾病进展并改善呼吸功能。这些实验中使用的动物细胞与人体剂量不相容。本研究旨在开发用于ALS治疗的同源人源性grp。该提案的目的是：1)证明人类GRPs在ALS动物模型中的行为与大鼠GRPs相似；2)开发用于纯化人类GRPs的抗体，以达到细胞治疗生产所需的规格；3)在动物安全性研究所需的良好实验室规范（GLP）条件下生产人类GRPs； 4)证明人类GRPs是安全的、无毒的、非致瘤性的动物模型。目的1、4和5将通过将人grp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将需要通过标准细胞纯化和培养技术根据GLP标准进行细胞生产。这些研究的成功完成将成为FDA寻求在ALS中进行临床试验的新药研究（IND）申请的基础。相关性（见说明书）：肌萎缩性侧索硬化症（ALS）是一种控制肌肉功能的神经细胞死亡的疾病，患者在3-5年内死亡，目前尚无治愈方法。该提案旨在通过开展这项新治疗方法的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，这一建议将导致一种治疗方法，将恢复正常功能的受影响的神经细胞，反过来将减缓或停止疾病的进展。

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.