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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。多发性硬化（MS）是一种中枢神经系统（CNS）的炎性脱髓鞘变性疾病。它是一种世界性疾病，影响美国约300，000人;它是一种年轻人的疾病，70-80%在20-40岁之间发病。根据临床病程、磁响应成像（MRI）扫描评估以及活检和尸检材料的病理学分析，MS是一种异质性疾病。该疾病表现为大量可能的缺陷组合，包括脊髓、脑干、颅神经、小脑、大脑和认知综合征。进行性残疾是大多数MS患者的命运，特别是当包括25年的前景时。一半的MS患者在发病后15年内需要拐杖行走。MS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。 目前还没有针对原发性进展型MS的获批疗法，也没有有效预防长期残疾的治疗方法。存在大量证据表明抗体和B细胞淋巴细胞在MS发病机制中的致病作用，并将B细胞鉴定为用于治疗MS的新型免疫疗法的适当靶点。利妥昔单抗特异性消除B细胞，并具有充分表征的安全性特征，这使其成为进一步阐明B-细胞在MS发病机制中的作用的潜在有吸引力的药理学试剂。细胞及其在MS病理生理学中的功能，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.