THERAPEUTIC REMYELINATION STRATEGIES IN A NOVEL MODEL OF MS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这种高度整合的多学科应用集中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，类似于人类的多发性硬化症，作为MS的病理生理和遗传模型，其病因和进展与非人类灵长类动物和啮齿类动物中的其他EAE和病毒模型更接近人类MS。我们的目标是使用这个模型来更好地了解γ-疱疹病毒如何触发MS;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MS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可抑制脱髓鞘病变中髓鞘再生的因子如透明质酸的积累。 我们的长期目标是开发JME作为测试MS基础的免疫和神经生物学过程的模型，并将该模型用于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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.