PROMOTION OF NERVE REGENERATION BY FRAGMENTS OF L1

描述：（改编自申请人摘要） 中枢神经系统（CNS）的损伤是最具破坏性的， 人类痛苦的代价。现在科学技术的最新进展 提供的工具，首次允许有系统的方法来修复 或再生受损的中枢神经系统轴突。此类工具包括各种工具等 神经营养和信号传导因子，细胞粘附分子，去抑制 药物、细胞和基因疗法以及可靠的动物模型， 神经创伤一些实验室报告说， 这些干预措施可以增强轴突再生和功能恢复 CNS损伤后。开发这种疗法的一个关键挑战是 促进神经再生的有效生物活性因子在 vivo. L1是一种神经细胞粘附分子（CAM），是一种有效的促进剂， 轴突的生长。该赠款的第一阶段建议综合 人L1片段作为Fc融合蛋白，并测试它们促进 神经突生长。然后将检测L1融合蛋白的 在大鼠急性脊髓损伤模型中的功能恢复。的 第一阶段研究是第二阶段计划的准备工作，我们将 系统地评价各种形式的人L1-Fc的活性， 优化这些分子在体内的剂量，并探索 慢性脊髓损伤模型中的L1-Fc。 拟议商业应用：不可用

DESCRIPTION: (adapted from applicant's abstract) Injuries to the central nervous system (CNS) are among the most devastating and costly of human afflictions. Recent advances in science and technology now provide tools which, for the first time, permit methodical approaches to repair or regenerate damaged CNS axons. Such tools include, among others, a variety of neurotrophic and signaling factors, cell adhesion molecules, disinhibiting agents, cell and gene-based therapies, and reliable animal models of neurotrama. Several laboratories have reported encouraging progress in applying such interventions to enhance axonal regeneration and functional recovery following CNS injury. A key challenge in the development of such therapies is the application of potent bioactive factors that promote nerve regeneration in vivo. L1 is a neuronal cell adhesion molecule (CAM) that is a potent promoter of axonal growth in culture. Phase I of this grant proposes to synthesize fragments of human L1 as Fc fusion proteins and test their ability to promote neurite outgrowth in culture. The L1 fusion proteins will then be tested for functional recovery in a model for acute spinal cord injury in the rat. The Phase I studies are preparatory to a Phase II program in which we will systematically evaluate the activities of various forms of human L1-Fc, optimize the dosage of these molecules in vivo, and explore the efficacy of L1-Fc in a model for chronic spinal cord injury. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE