Non-immunosuppressive rheumatoid arthritis DMARD

摘要 本研究旨在通过靶向治疗RA，开发一种新的非免疫抑制性生物疗法。 成纤维细胞样滑膜细胞，局部关节衬里细胞，实质上有助于关节破坏， 类风湿性关节炎（RA）。免疫抑制类抗风湿药物的研究进展 （DMARDs）极大地改善了RA患者的生活质量;然而， 目前可用的RA药物仍不能充分控制疾病活动。有必要 用于RA的新型非免疫抑制疗法，其可以单独使用或与当前的 DMARD。为了满足这一需求，我们正在寻求靶向成纤维细胞样滑膜细胞作为非- RA免疫抑制剂选择。在这里，我们将证明我们的生物减少FLS迁移和入侵 并逆转小鼠的关节炎。该项目解决了RA的一个主要未满足的医疗需求，即缺乏非 用于控制疾病活动的免疫抑制疗法。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，以进一步开发铅和表征其临床前 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.