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CNS自身免疫损伤相关。拟议的多学科研究项目将侧重于开发和表征一种新的药理学干预策略，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CNS炎症、预防有髓鞘轴突的损失和损伤以及刺激受损轴突的再生和髓鞘再生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。这些实验将确定治疗在终止和/或预防自身免疫性视神经炎相关神经元损失和视觉功能保留方面的功效，并生成数据以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，我们将测试这样的假设：拟议的治疗策略可以针对和补救特定表型，包括视神经炎和多发性硬化症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力障碍和功能缺陷。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，作为该项目的总体目标。这种治疗方法的自身免疫性视神经炎的重点是抑制中枢神经系统自身免疫反应，神经保护，轴突再生和髓鞘通过不同的机制。它具有预防和治疗的潜力，并补充现有的治疗设计和原理，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，美国约40万人。在多发性硬化症中，视神经（将眼睛连接到大脑并由此使视力成为可能的神经）的变性或损伤是美国和世界范围内生活质量和生产力损失的主要原因。该项目提出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。随着视神经变性影响到越来越多的美国人口，包括受医疗保健提供差异影响的少数民族，确定原因，作用机制和随后的潜在治疗策略将有助于改善医疗保健，健康和身体表现。

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.