RITUXIMAB (MABTHERA/RITUXAN) IN ADULTS WITH PRIMARY PROGRESSIVE MS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。多发性硬化(MS)是一种人类中枢神经系统(CNS)的炎症性和脱髓鞘退行性疾病。它是一种世界性疾病，影响着美国约30万人；它是一种年轻人的疾病，70%-80%的人在20-40岁之间发病。多发性硬化症是一种异质性疾病，基于临床病程、磁反应成像(MRI)扫描评估以及活检和尸检材料的病理分析。这种疾病表现为大量可能的缺陷组合，包括脊索、脑干、脑神经、小脑、大脑和认知综合征。进行性残疾是大多数多发性硬化症患者的命运，特别是当考虑到25年的远景时。一半的多发性硬化症患者在发病后15年内需要拐杖行走。多发性硬化症是年轻人和中年人神经功能障碍的主要原因，直到过去十年，还没有已知的有益治疗方法。没有批准的治疗原发进展性多发性硬化症的方法，也没有有效预防长期残疾的治疗方法。已有大量证据表明抗体和B细胞淋巴细胞在MS的发病机制中起致病作用，并确定B细胞是治疗MS的新型免疫疗法的合适靶点。Rituximab可以特异性地去除B细胞，并且具有良好的安全性，使其成为潜在的有吸引力的药理学制剂，进一步阐明B细胞在MS病理生理学中的角色和功能，并测试B细胞耗竭疗法的治疗潜力。

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. Multiple Sclerosis (MS) is an inflammatory and demyelinating degenerative disease of the human central nervous system (CNS). It is a worldwide disease that affects approximately 300,000 persons in the United States; it is a disease of young adults, with 70-80% having onset between 20-40 years old. MS is a heterogeneous disorder based on clinical course, magnetic response imaging (MRI) scan assessment, and pathology analysis of biopsy and autopsy material. The disease manifests itself in a large number of possible combinations of deficits, including spinal chord, brainstem, cranial nerve, cerebellar, cerebral and cognitive syndromes. Progressive disability is the fate of most patients with MS, especially when a 25-year perspective is included. Half of MS patients require a cane to walk within 15 years of disease onset. MS is a major cause of neurological disability in young and middle-aged adults and, until the past decade, has had no known beneficial treatments. There are no approved therapies for primary progressive MS and no treatments effective for the prevention of long-term disability. Substantial evidence exists for a pathogenic role of antibodies and B-cell lymphocytes in the pathogenesis of MS and identifies B-cells as an appropriate target for novel immunotherapies for the treatment of MS. Rituximab specifically ablates B-cells and has a well-characterized safety profile that makes it a potentially attractive pharmacological agent to further elucidate the role of B-cells and their functions in MS pathophysiology and to test the therapeutic potential of a B-cell depleting therapy.