Novel mechanism of action as therapeutic strategy for optic neuritis

作为视神经炎治疗策略的新作用机制

基本信息

批准号：
8675259
负责人：
Peter Koulen
金额：
$ 36.75万
依托单位：
UNIVERSITY OF MISSOURI KANSAS CITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8675259
关键词：
Acute Address Affect Aftercare Animal Model Autoimmune Process Autoimmunity Axon Behavioral Biological Biological Preservation Biological Products Blindness Brain CNS autoimmune disease CNS autoimmunity CNS degeneration Cell physiology Cells Characteristics Clinical Clinical Trials Combined Modality Therapy Complement Complex Complication Confocal Microscopy Cytophotometry Data Degenerative Disorder Detection Development Diagnosis Diagnostic Differential Diagnosis Disease Disease Progression Disease model Dose Drug Combinations Event Experimental Models Eye Generic Drugs Genomics Goals Healthcare Heat shock proteins Human Human Pathology Immunoblot Analysis In Vitro Inflammation Inflammatory Interdisciplinary Study Intervention Knowledge Measures Mediating Methods Minority Modeling Multiple Sclerosis Myelin Myelin Proteins Natural regeneration Nerve Nerve Degeneration Neurons Optic Nerve Optic Neuritis Pathologic Pathology Pathway interactions Patients Pattern Performance Pharmaceutical Preparations Phase Phenotype Population Preclinical Testing Prevention Process Productivity Quality of life Rattus Regimen Research Research Project Grants Resveratrol Retina Rodent Model Sequential Treatment Signal Transduction Staging Structure Testing Therapeutic Therapeutic Intervention Toxic effect Treatment Efficacy Treatment Protocols United States Vision Visual Acuity Visual impairment autoimmune optic neuritis axon regeneration axonal degeneration base care burden clinical phenotype clinically relevant disease phenotype drug development functional disability functional outcomes geranylgeranylacetone health care delivery human disease immunoreactivity improved in vivo inhibitor/antagonist innovation neuron loss neuroprotection novel novel therapeutics optic nerve regeneration physical conditioning prenylation prevent regenerative remyelination repaired research study small molecule therapy design therapy development trans-resveratrol treatment strategy

项目摘要

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.

描述（由申请人提供）：视神经和视网膜引起的视网膜的变性或损害是美国视觉丧失和失明的主要原因，在全球范围内与多发性硬化症和对中枢神经系统的自身免疫性损害有关。拟议的多学科研究项目将重点介绍一种新型药理干预策略的开发和表征，该策略结合了药物来控制自身免疫性神经神经炎的结构和功能变性。该研究的主要目标是抑制CNS炎症，预防骨髓轴突的损失和损伤以及刺激再生和对受损轴突的再生。为此，将在人类自身免疫性神经炎的既定模型中对新的治疗策略进行临床前测试。这些实验将确定治疗在终止和/或预防自身免疫神经炎相关的神经元丧失和视觉功能的保留方面的功效，并生成数据以支持对1或2期临床试验的可行性并将阳性发现的可行性。具体而言，我们将检验以下假设：拟议的治疗策略CN靶标和治疗特定表型，其中包括在视神经炎的不同阶段和多发性硬化症中遇到的单独病理的组合，从而改善了与疾病相关的视觉障碍和功能缺陷。确定神经元的生存力和有关相关治疗参数的获得的知识将表明该方法的潜在纠正自身免疫性神经炎作为项目的总体目标。这种自身免疫性视神经炎的疗法专注于通过不同机制抑制CNS自身免疫反应性，神经保护性，轴突再生和透明式化。它具有预防和治疗性的潜力，并补充了现有的治疗设计和理由，以解决自身免疫性神经炎治疗的其他方面。