Treatment of arthritis with interleukins

用白细胞介素治疗关节炎

• 批准号: 6585623
• 负责人: VIT LAUERMANN
• 金额: $ 17.5万
• 依托单位: RUBICON LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2004-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6585623
• 关键词: active sites; antiarthritic agent; antiinflammatory agents; biotherapeutic agent; chemical synthesis; cytokine receptors; drug design /synthesis /production; interleukin 4; metalloendopeptidases; protein engineering; recombinant proteins; rheumatoid arthritis

DESCRIPTION (provided by applicant): The overall goal of this project is to develop a therapeutic method for targeted delivery of IL-4 to arthritic joints. Rheumatoid arthritis is an autoimmune disease characterized by progressive cartilage and bone erosion. Cytokines are important modulators of immune responses and IL-4 is an attractive cytokine for treating arthritis. Local administration of IL-4 has therapeutic effects in patients with moderate arthritis. However, the therapeutic efficacy of the cytokine is limited due to its toxicity. To improve the cytokine therapeutic effect, its concentration in a disease site has to be increased without causing undesirable side effects. The proposed method suppresses the biological activity of the administered cytokine until it reaches proximity of a target cell. The cytokine is then rendered active and concentrates in a disease site. The cytokine concentration in arthritic joints can reach levels that have desired therapeutic effects without systemic toxicity. This targeted delivery approach can be adapted for other cytokines and diseases and can be used as adjuvant to other treatments or stand alone. In Phase I we will develop the biological reagents and test them in vitro. We will use these reagents in Phase II in preclinical studies evaluating treatment of arthritis in animals.

描述（由申请人提供）：本项目的总体目标是开发一种将IL-4靶向递送至关节炎关节的治疗方法。风湿性关节炎是一种自身免疫性疾病，其特征是进行性软骨和骨侵蚀。细胞因子是免疫应答的重要调节剂，并且IL-4是用于治疗关节炎的有吸引力的细胞因子。局部给予IL-4对中度关节炎患者具有治疗作用。然而，细胞因子的治疗功效由于其毒性而受到限制。为了提高细胞因子的治疗效果，必须增加其在疾病部位中的浓度而不引起不期望的副作用。所提出的方法抑制施用的细胞因子的生物活性，直到其到达靶细胞附近。然后使细胞因子活化并集中在疾病部位。关节炎关节中的细胞因子浓度可以达到具有期望的治疗效果而没有全身毒性的水平。这种靶向递送方法可以适用于其他细胞因子和疾病，并且可以用作其他治疗的佐剂或独立使用。在第一阶段，我们将开发生物试剂并进行体外测试。我们将在II期临床前研究中使用这些试剂，评估动物关节炎的治疗。