Non-immunosuppressive rheumatoid arthritis DMARD

非免疫抑制性类风湿性关节炎 DMARD

基本信息

批准号：
10761242
负责人：
Stephanie Stanford
金额：
$ 27.44万
依托单位：
KNOUBIS BIO, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-21 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10761242
关键词：
Address Antibodies Antirheumatic Agents Arthritis Binding Biological Biological Assay Biological Response Modifier Therapy Businesses California Cartilage Cell Line Cells Collagen Arthritis Data Development Disease Dissociation Effectiveness Epitopes Fibroblasts Funding Glycosaminoglycans Goals Human Immune Immune system Immunoglobulin Domain Immunosuppression Immunosuppressive Agents Invaded Investigational Drugs Janus kinase Joints Knock-out Knockout Mice Laboratories Lead Length Ligands Medical Membrane Methotrexate Modeling Monoclonal Antibodies Morbidity - disease rate Mus Mutate N-terminal National Institute of Arthritis, and Musculoskeletal, and Skin Diseases Patients Phage Display Pharmaceutical Preparations Phase Phosphoric Monoester Hydrolases Protein Tyrosine Kinase Protein Tyrosine Phosphatase Proteoglycan Quality of life Recombinants Research Project Grants Rheumatoid Arthritis Side Signal Transduction Inhibition TNF gene Therapeutic Universities arthritis therapy disorder control extracellular immunoregulation improved innovation joint destruction joint injury kinase inhibitor migration mouse model novel pre-clinical preclinical efficacy preclinical safety receptor syndecan-4 synergism

项目摘要

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.

抽象的该提案的重点是开发一种针对 RA 的新型非免疫抑制生物疗法成纤维细胞样滑膜细胞，局部关节衬里细胞，在运动过程中对关节破坏有很大贡献类风湿性关节炎（RA）。免疫抑制剂缓解疾病抗风湿药物的开发（DMARD）显着改善了 RA 患者的生活质量；然而很大一部分患者目前可用的 RA 药物仍无法充分控制疾病活动。有需要用于治疗 RA 的新型非免疫抑制疗法，可单独使用或与现有疗法联合使用 DMARD。为了满足这一需求，我们正在寻求将成纤维细胞样滑膜细胞作为非 RA 的免疫抑制选择。在这里，我们将展示我们的生物制剂可减少 FLS 迁移和入侵并逆转小鼠的关节炎。该项目解决了 RA 中一个未满足的主要医疗需求，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，以进一步开发先导药物并表征其临床前特征功效和安全性。