Treatment of ALS based on transplantation of glial restricted progenitors

基于神经胶质限制性祖细胞移植的 ALS 治疗

• 批准号: 9295061
• 负责人: Piotr Walczak
• 金额: $ 35.24万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9295061
• 关键词: Adult; Allografting; Amyotrophic Lateral Sclerosis; Animal Experiments; Animals; Astrocytes; Behavior; Biodistribution; Bioluminescence; Brain; Catheters; Cell Therapy; Cell Transplantation; Cells; Cerebrovascular system; Clinical; Data; Development; Diagnosis; Diagnostic radiologic examination; Engineering; Engraftment; Family suidae; Genetic; Goals; Homing; Homologous Transplantation; Human; Image; Imaging Techniques; Infusion procedures; Injectable; Intervention; Longevity; Magnetic Resonance Imaging; Measures; Methodology; Methods; Modeling; Motor; Mus; Neonatal; Nervous System Physiology; Neuraxis; Neurobiology; Neurodegenerative Disorders; Neuroglia; Neurologic; Oligodendroglia; Pathology; Patients; Play; Procedures; Property; Rattus; Regenerative Medicine; Reporter Genes; Reporting; Research; Rodent; Rodent Model; Role; Safety; Shivering; Source; Stem cells; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Transplantation; base; clinically relevant; cohort; dysmyelination; effective therapy; fetal; image guided; immunogenicity; improved; instrumentation; migration; motor neuron function; mutant; myelination; nervous system disorder; novel therapeutics; precursor cell; progenitor; programs; public health relevance; restoration; stem; treatment strategy; ventricular system

 DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder without a cure. Patients who suffer from ALS typically die within two-to-five years of diagnosis. Recent progress in regenerative medicine has raised hope for a breakthrough. The significant role of glia for the proper function of motor neurons has been recently reported, and efficient methods to isolate glial-restricted precursors (GRP) have been established. It has been shown in rodent models that GRPs of fetal origin display the highest therapeutic potential among all other sources, because they are characterized by extensive engraftment, differentiation, and robust therapeutic effect. In this project, we propose to use fetl GRPs for the treatment of ALS. The Allografting of GRPs in pigs is particularly attractive, as it will be performed in a clinically relevant setting, including utilization of catheter-based cell delivery, with a clinical MR scanner for cell tracking and assessment of immunogenicity/immunoprotection. The application of the latest developments in neurobiology, interventional neuroradiology, and regenerative medicine should result in a long-awaited cure for ALS.

 描述（由申请人提供）：肌萎缩侧索硬化症（ALS）是一种无法治愈的进行性神经退行性疾病。患有ALS的患者通常在诊断后两到五年内死亡。再生医学的最新进展带来了突破的希望。近年来，有关胶质细胞在运动神经元正常功能中的重要作用的报道不断增多，并建立了分离胶质限制性前体细胞（GRP）的有效方法。在啮齿动物模型中已经显示，胎儿来源的GRP在所有其他来源中显示出最高的治疗潜力，因为它们的特征在于广泛的植入、分化和稳健的治疗效果。在这个项目中，我们建议使用fetl GRP治疗ALS。猪中GRP的同种异体移植特别有吸引力，因为它将在临床相关环境中进行，包括利用基于导管的细胞递送，使用临床MR扫描仪进行细胞跟踪和免疫原性/免疫保护评估。应用神经生物学、介入神经放射学和再生医学的最新进展，应该会导致人们期待已久的ALS治愈方法。