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Glial Progenitor Cells for Treatment of ALS

神经胶质祖细胞治疗 ALS

基本信息

批准号：
8145663
负责人：
NICHOLAS J MARAGAKIS
金额：
$ 131.72万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8145663
关键词：
Affect Amyotrophic Lateral Sclerosis Animal Model Animals Antibodies Antibody Dissociations Antibody Formation Atrophic Behavioral Biodistribution Biotechnology Biotin Brain Cell Proliferation Cells Cervical spinal cord structure Cessation of life Clinical Clinical Chemistry Clinical Trials Contracts Deterioration Devices Disease Disease Progression Dose Drug Formulations Event Forelimb Germany Glial Fibrillary Acidic Protein Growth Harvest Hematology Hematoxylin and Eosin Staining Method Histological Techniques Histology Human Immune Implant In Vitro Instruction Lead Length Limb structure Magnetism Measures Methods Microspheres Modeling Motor Neurons Muscle Muscle function Nerve Neurodegenerative Disorders Neurons Nude Rats Onset of illness Organ Outcome Paralysed Pharmaceutical Preparations Phenotype Primary Lateral Sclerosis Process Production Published Comment Rattus Recovery Research Personnel Research Proposals Respiratory Diaphragm Respiratory physiology Running Safety Shipping Ships Spinal Cord Staining method Stains Stem cells Sterility Stimulus Testing Therapeutic Therapeutic Uses Time Tissues Toxicology Translational Research Transplantation Tumor-Derived Tumorigenicity Urinalysis Vial device base behavior observation cGMP production design good laboratory practice grasp gray matter illness length immunosuppressed improved novel therapeutic intervention patient population polysialyl neural cell adhesion molecule programs research study safety study success tumor young adult

项目摘要

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Lou Gehrig病）的治疗药物。ALS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。对特定肌肉的神经刺激的丧失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人群的生存期为3至5年。目前还没有找到治愈ALS的方法。在ALS的动物模型中，已经显示GRP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给药不相容。该提案旨在开发用于ALS治疗用途的同源人源GRP。本提案的目的是1）证明人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GRP的抗体，使其达到用于细胞治疗生产所需的规格，3）在动物安全性研究所需的良好实验室规范（GLP）条件下生产人GRP，以及4）证明人GRP是安全、无毒的，和非致瘤素动物模型。目的1、4和5将通过将人GRP植入相关动物模型的脊髓中并评估其在细胞和行为水平上的作用来实现。目标2将通过标准抗体生产和纯化方法实现，而目标3将需要通过根据GLP标准进行的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FDA寻求在ALS中进行临床试验的新药研究（IND）申请奠定基础。相关性（参见说明）：肌萎缩侧索硬化症（ALS）是一种无法治愈的疾病，其中控制肌肉功能的神经细胞死亡，导致3-5年内死亡。该提案旨在通过进行开始这种新的治疗方法的临床试验所需的研究来开发用于治疗这种毁灭性疾病的细胞疗法。如果成功的话，这一建议将导致一种治疗方法，这种治疗方法将恢复受影响的神经细胞的正常功能，从而减缓或停止疾病的进展。