Non-immunosuppressive rheumatoid arthritis DMARD

非免疫抑制性类风湿性关节炎 DMARD

• 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
• 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

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.

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 疗效和安全性。