Non-immunosuppressive rheumatoid arthritis DMARD

摘要 本研究旨在开发一种新的靶向非免疫抑制生物治疗类风湿关节炎的方法。 成纤维细胞样滑膜细胞，局部关节衬里细胞，在 类风湿关节炎(RA)。免疫抑制剂、抗风湿病改良剂的研究进展 (DMARDS)极大地改善了RA患者的生活质量；然而，很大一部分患者 仍然不能达到对目前可用的RA药物的疾病活动的充分控制。有必要 用于治疗RA的新的非免疫抑制疗法，这些疗法可以单独使用或与电流联合使用 DMARDS。为了满足这一需求，我们正在寻求将成纤维样滑膜细胞作为一种非 类风湿关节炎的免疫抑制选择。在这里，我们将展示我们的生物减少FLS迁移和侵袭 并逆转小鼠的关节炎。该项目解决了RA一个主要的未得到满足的医疗需求，即缺乏非 控制疾病活动性的免疫抑制疗法。一旦我们在此期间获得概念验证数据 第一阶段项目，我们将申请第二阶段资金，以进一步发展Lead并描述其临床前特征 有效性和安全性。

ABSTRACT This proposal is focused on development of a novel non-immunosuppressive biologic therapy for RA by targeting fibroblast-like synoviocytes, local joint-lining cells that substantially contribute to joint destruction during rheumatoid arthritis (RA). The development of immunosuppressant disease-modifying anti-rheumatic agents (DMARDs) has dramatically improved the quality of life of RA patients; however a large proportion of patients still fail to reach sufficient control of disease activity on the currently available RA medications. There is a need for novel non-immunosuppressive therapies for RA that can be used alone or in combination with current DMARDs. To address this need, we are seeking to target fibroblast-like synoviocytes as a non- immunosuppressive option for RA. Here, we will demonstrate our biologic reduces FLS migration and invasion and reverses arthritis in mice. This project addresses a major unmet medical need in RA, the lack of non- immunosuppressive therapies for controlling disease activity. Once we obtain proof-of-concept data during this Phase I project, we will apply for Phase II funding to further develop the lead and characterize its preclinical efficacy and safety.