Novel mechanism of action as therapeutic strategy for optic neuritis

描述(申请人提供)：视神经炎引起的视神经和视网膜的退化或损伤是美国和世界范围内与多发性硬化症和中枢神经系统自身免疫损伤相关的视力丧失和失明的主要原因。拟议的多学科研究项目将集中于开发和表征一种新的药物干预策略，该策略结合药物来控制自身免疫性视神经炎的结构和功能退化。抑制中枢神经系统炎症，防止有髓轴突的丢失和损伤，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，将在已建立的人类自身免疫性视神经炎模型中进行新治疗策略的临床前测试。这些实验将确定在终止和/或预防自身免疫性视神经炎相关神经元丢失和保护视觉功能方面的治疗效果，并产生支持可行性的数据，并将阳性结果转移到第一或第二阶段临床试验。具体地说，我们将测试这样一个假设，即拟议的治疗策略针对并补救特定的表型，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，导致与疾病相关的视力障碍和功能障碍的改善。神经元活性的测定和相关治疗参数的获得性知识将表明该方法作为该项目的总体目标治疗自身免疫性视神经炎的潜力。这种治疗自身免疫性视神经炎的方法侧重于通过不同的机制抑制中枢神经系统自身免疫反应、神经保护、轴突再生和重新髓鞘形成。它具有预防和治疗的潜力，并补充现有的治疗设计和理论基础，解决自身免疫性视神经炎治疗的其他方面。 公共卫生相关性：多发性硬化症影响全球约250万人和美国约40万人。在多发性硬化症中，视神经的退化或损伤是美国和世界范围内生活质量和生产力丧失的主要原因。视神经连接眼睛和大脑，从而使视力成为可能。该项目建议确定控制疾病进展的联合药物治疗的新靶点的身份和功能。由于视神经退化影响到美国人口中相当大且越来越多的部分，包括受医疗保健服务差异影响的少数族裔，确定原因、作用机制以及随后可能的治疗策略将有助于改善医疗保健、健康和身体状况。

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.