Tenascin-C-Fragments for Spinal Cord Regeneration

用于脊髓再生的腱蛋白-C 片段

• 批准号: 6337543
• 负责人: ANDREW R BLIGHT
• 金额: $ 10万
• 依托单位: ACORDA THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6337543
• 关键词: drug design /synthesis /production; drug screening /evaluation; extracellular matrix; immunocytochemistry; laboratory rat; nervous system disorder chemotherapy; nervous system regeneration; neuropharmacology; nonhuman therapy evaluation; spinal cord injury; tenascin

The goal of this project is to conduct pre-clinical tests of components of the extracellular matrix molecule tenascin-C that offer potential as therapeutics for enhancing nerve fiber regeneration. This may lead to the development of a treatment for spinal cord injury, a devastating condition for which there are no reparative treatments available. The study is based on a new understanding of how the fhA-D component of tenascinC regulates neurite outgrowth. The project will examine effects of delivering fnA-D recombinant protein, or its active peptide sequence (VFDNFVLK ) to the site of an experimental spinal cord injury. Hemisection of the dorsal thoracic (T9) spinal cord of rats will be used to examine the response of corticospinal and primary afferent nerve fibers to transection and treatment with the protein and peptide. Groups of animals will be assigned to treatment with fnA-D, VFDNFVLK, or buffer delivered intrathecally for two weeks from an implanted osmotic pump. Hind limb function will be monitored with a grid-walking test. The primary measure of treatment effect will be immunohistological analysis of axonal regeneration, using Cholera toxin injected either into the motor cortex or into the sciatic nerves. Effects on regeneration of axons will be examined qualitatively and measured quantitatively. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

该项目的目的是进行组件的临床前测试 细胞外基质分子Tenascin-C的潜力 作为增强神经纤维再生的治疗学。这可能会导致 开发治疗脊髓损伤的治疗 没有可用的赔偿治疗。该研究是基于新的 了解Tenascinc的FHA-D成分如何调节神经突 出生。该项目将检查提供FNA-D重组的影响 蛋白质或其活性肽序列（VFDNFVLK） 实验性脊髓损伤。背胸部（T9）脊柱的半部 大鼠的绳索将用于检查皮质脊髓和原发性的反应 传入的神经纤维与蛋白质的横切和治疗 肽。动物组将被分配给FNA-D，VFDNFVLK， 或从植入的渗透泵持胸前两周的缓冲液。 后肢功能将通过网格步行测试进行监测。主要 治疗效果的度量将是轴突的免疫组织学分析 再生，使用注射到运动皮质或进入的霍乱毒素 坐骨神经。将检查对轴突再生的影响 定性和定量测量。 拟议的商业应用程序：不可用