THERAPEUTIC REMYELINATION STRATEGIES IN A NOVEL MODEL OF MS

多发性硬化症新模型中的髓鞘再生治疗策略

• 批准号: 8357821
• 负责人: Larry S. Sherman
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357821
• 关键词: Animals; Disease; Encephalomyelitis; Etiology; Experimental Autoimmune Encephalomyelitis; Funding; Genes; Genetic Models; Genetic Polymorphism; Goals; Grant; Herpesviridae Infections; Human; Hyaluronan; Immunologic Tests; Japanese Population; Lesion; Link; Macaca; Modeling; Multiple Sclerosis; Multiple Sclerosis Lesions; National Center for Research Resources; Natural regeneration; Neurobiology; Primates; Principal Investigator; Process; Research; Research Infrastructure; Resources; Rodent; Source; Testing; Therapeutic; United States National Institutes of Health; Viral; astrogliosis; cost; gammaherpesvirus; multidisciplinary; nonhuman primate; novel; pre-clinical

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This highly integrated, multidisciplinary application is focused on developing Japanese Macaque Encephalomyelitis (JME), a disease that occurs spontaneously in Japanese macaques and which mimics multiple sclerosis in humans, as a pathophysiogical and genetic model of MS whose etiology and progression more closely resemble MS in humans than other EAE and viral models in non-human primates and rodents. We aim to use this model to better understand how gamma-herpesviruses trigger MS; whether polymorphisms in gene loci that have been linked to MS in humans also predispose JMs to JME; to evaluate the lesions in both symptomatic and subclincal animals to determine if they model numerous aspects of human MS lesions; and to test if gamma-herpesvirus infection directly influences astrogliosis and the accumulation of factors, such as hyaluronan, that can inhibit remyelination in demyelinated lesions. Our long-term goal is to develop JME as a model for testing immunological and neurobiological process underyling MS, and to use this model in pre-clinical screens of novel agents with the potential to inhibit MS attacks and to promote remyelination and regeneration.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 这一高度集成的多学科应用专注于开发日本猕猴脑脊髓炎 (JME)，这是一种在日本猕猴中自发发生的疾病，模仿人类多发性硬化症，作为多发性硬化症的病理生理学和遗传模型，其病因和进展更接近于多发性硬化症。人类比其他 EAE 和非人类灵长类动物和啮齿动物病毒模型更有效。我们的目标是利用这个模型更好地了解 γ-疱疹病毒如何引发多发性硬化症；与人类 MS 相关的基因位点的多态性是否也使 JM 易患 JME；评估有症状和亚临床动物的病变，以确定它们是否模拟了人类多发性硬化症病变的许多方面；并测试γ-疱疹病毒感染是否直接影响星形胶质细胞增生和透明质酸等因子的积累，这些因子可以抑制脱髓鞘病变中的髓鞘再生。 我们的长期目标是开发 JME 作为测试 MS 下的免疫和神经生物学过程的模型，并使用该模型来临床前筛选具有抑制 MS 攻击和促进髓鞘再生和再生潜力的新型药物。