PROMOTION OF NERVE REGENERATION BY FRAGMENTS OF L1

描述：(改编自申请者摘要) 中枢神经系统(CNS)的损伤是最具破坏性的和 人类痛苦的代价。当今科学技术的最新进展 提供工具，首次允许采用有条不紊的方法修复 或再生受损的中枢神经系统轴突。除其他工具外，这些工具包括各种 神经营养和信号因子，细胞黏附分子，去抑制 药物、基于细胞和基因的治疗以及可靠的动物模型 神经衰弱。几个实验室报告在应用方面取得了令人鼓舞的进展 这种促进轴突再生和功能恢复的干预措施 中枢神经系统损伤后。开发这种疗法的一个关键挑战是 促进神经再生的高效生物活性因子在神经再生中的应用 活着。L1是一种神经细胞黏附分子(CAM)，是一种强有力的启动子 培养中的轴突生长。这笔赠款的第一阶段建议合成 人L1基因片段作为Fc融合蛋白并检测其促进能力 轴突在培养中长出。然后对L1融合蛋白进行检测 大鼠急性脊髓损伤模型的功能恢复。这个 第一阶段的研究是为第二阶段计划做准备，在该计划中，我们将 系统评价各种形式的人L1-Fc的活性， 优化这些分子在体内的剂量，并探索其疗效 L1-Fc在慢性脊髓损伤模型中的应用。 建议的商业应用：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