THERAPEUTIC REMYELINATION STRATEGIES IN A NOVEL MODEL OF MS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这一高度集成的多学科应用程序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，它模仿人类的多发性硬化症，作为多发性硬化症的病理生理和遗传模型，其病因和进展更类似于人类的多发性硬化症，而不是其他EAE和非人灵长类和啮齿类动物的病毒模型。我们的目标是使用这个模型来更好地了解伽玛疱疹病毒是如何触发多发性硬化症的；人类中与多发性硬化症相关的基因位点的多态是否也使JMS易患JME；评估有症状和临床下动物的损害以确定它们是否模拟了人类多发性硬化症损害的许多方面；以及测试伽玛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可以抑制脱髓鞘病变中重新髓鞘形成的因子的积累。我们的长期目标是开发JME作为测试MS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发作、促进髓鞘再生和再生的潜在新药。

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.