Glial Progenitor Cells for Treatment of ALS

神经胶质祖细胞治疗 ALS

• 批准号: 8329923
• 负责人: NICHOLAS J MARAGAKIS
• 金额: $ 97.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8329923
• 关键词: Glial; Progenitor; Cells; Treatment; ALS

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.

描述（由申请人提供）：这是一项转化研究提案，旨在开发神经胶质限制性祖细胞（GRP）作为治疗肌萎缩侧索硬化症（ALS；也称为卢伽雷氏病）的疗法。 ALS 是一种神经退行性疾病，同时影响上运动神经元和下运动神经元。这种疾病的特点是运动神经元进行性恶化和丧失。特定肌肉失去神经刺激会导致萎缩和进行性无力，从而导致瘫痪。已评估的大多数患者群体的生存期为 3 至 5 年。目前尚未找到 ALS 的治愈方法。在 ALS 动物模型中，研究表明 GRP 可以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。该提案旨在开发用于 ALS 治疗的同源人源 GRP。该提案的目的是 1) 证明人类 GRP 在 ALS 动物模型中的行为与大鼠 GRP 相似，2) 开发用于纯化人类 GRP 的抗体，使其达到其在细胞治疗生产中使用所需的规格 3) 生产人类 GRP GRP 符合动物安全研究所需的良好实验室规范 (GLP) 条件，4) 证明人类 GRP 是安全、无毒、无致瘤性的动物模型。目标 1,4 和 5 将通过将人类 GRP 植入相关动物模型的脊髓并评估其在细胞和行为水平上的影响来实现。目标 2 将通过标准抗体生产和纯化方法来实现，而目标 3 将需要根据 GLP 标准进行标准细胞纯化和培养技术进行细胞生产。这些研究的成功完成将为向 FDA 寻求进行 ALS 临床试验的研究性新药 (IND) 申请奠定基础。相关性（参见说明）：肌萎缩侧索硬化症 (ALS) 无法治愈，这种疾病是控制肌肉功能的神经细胞死亡，导致 3-5 年内死亡。该提案旨在通过开展这种新型治疗方法的临床试验所需的研究来开发一种治疗这种破坏性疾病的细胞疗法。如果成功，该提议将导致一种疗法，使受影响的神经细胞恢复正常功能，从而减缓或阻止疾病的进展。