Novel mechanism of action as therapeutic strategy for optic neuritis

描述（由申请人提供）：视神经炎引起的视神经和视网膜变性或损伤是美国和世界范围内视力丧失和失明的主要原因，与多发性硬化症和中枢神经系统自身免疫损伤有关。拟议的多学科研究项目将侧重于开发和表征一种新的药物干预策略，结合药物来控制自身免疫性视神经炎的结构和功能变性。抑制中枢神经系统炎症，防止髓鞘轴突的丢失和损伤，刺激受损轴突的再生和再髓鞘形成是本研究的主要目标。为此，新的治疗策略的临床前测试将在已建立的人类自身免疫性视神经炎模型中进行。这些实验将确定治疗在终止和/或预防自身免疫性视神经炎相关的神经元丢失和视觉功能保存方面的疗效，并生成数据来支持可行性，并将阳性结果转移到1期或2期临床试验。具体来说，我们将验证所提出的治疗策略可以靶向和治疗特定表型的假设，包括在视神经炎和多发性硬化症的不同阶段遇到的不同病理的组合，从而改善与该疾病相关的视觉损害和功能缺陷。神经元活力的测定和获得的相关治疗参数的知识将表明该方法治疗自身免疫性视神经炎的潜力，这是该项目的总体目标。这种治疗自身免疫性视神经炎的方法侧重于通过不同机制抑制中枢神经系统自身免疫反应性、神经保护、轴突再生和髓鞘再生。它具有预防和治疗的潜力，并补充现有的治疗设计和基础，解决自身免疫性视神经炎治疗的其他方面。

DESCRIPTION (provided by applicant): Degeneration or damage of the optic nerve and the retina due to optic neuritis is a leading cause of visual loss and blindness in the United States and worldwide associated with multiple sclerosis and autoimmune damage to the CNS. The proposed multidisciplinary research project will focus on the development and characterization of a novel pharmacological intervention strategy that combines drugs to control structural and functional degeneration in autoimmune optic neuritis. Suppression of CNS inflammation, prevention of loss and damage of myelinated axons, and stimulation of regeneration and remyelination of damaged axons are the primary goals of the study. To this end, preclinical testing of the new therapeutic strategy will be performed in established models of human autoimmune optic neuritis. These experiments will determine efficacy of treatment in terminating and/or preventing autoimmune optic neuritis associated neuronal loss and preservation of visual function, and to generate data to support feasibility for and move positive findings to phase 1 or 2 clinical trials. Specifically, we will test the hypothesis that the proposed treatment strategy cn target and remedy specific phenotypes that include combinations of separate pathologies encountered during distinct stages of optic neuritis and multiple sclerosis, leading to improvement of visual impairment and functional deficits associated with the disease. The determination of neuronal viability and the acquired knowledge on associated therapeutic parameters will indicate the potential of the method to remedy autoimmune optic neuritis as the overall goal of the project. This therapy approach for autoimmune optic neuritis focuses on suppression of CNS autoimmunoreactivity, neuroprotection, axon regeneration and remyelination via different mechanisms. It has the potential to be both preventative and therapeutic and to complement existing treatment designs and rationales addressing other aspects of autoimmune optic neuritis treatment. PUBLIC HEALTH RELEVANCE: Multiple sclerosis affects approximately 2.5 million people worldwide and approximately 400,000 people in the United States. In multiple sclerosis, degeneration or damage of the optic nerve, the nerve that connects the eye to the brain and thereby makes vision possible, is a leading cause of loss of quality of life and productivity in th United States and worldwide. The project proposes the determination of the identity and function of novel targets for combination drug treatment that controls disease progression. As degeneration of the optic nerve affect significant and increasing portions of the U.S. population including minorities affected by disparities in health care delivery, determining causes, mechanisms of action and subsequently potential treatment strategies will contribute to improving health care, health and physical performance.