Novel Nontoxic Therapeutic Interventions for Autoimmune Inflammatory Disease

项目总结/摘要 尽管自身免疫性疾病的进展和治疗，但仍然存在未满足的对更安全的治疗的需求。 以及更有效的治疗方法。这些进步不能 在我们对疾病机制的知识和理解没有重大进展的情况下发生。 在自身免疫卓越中心的支持下，我们组建了一个财团， 5年前，优秀的合作网站成立了“费恩斯坦医学研究所 自身免疫性疾病临床研究中心。我们中心的首要主题是 自身免疫性疾病中发生的组织损伤通常是多种疾病的最终结果， 多余的炎症途径和介质（细胞因子）。我们仍然认为， 调节多种炎症介质的抗炎方法将与 我们将寻求具有更好的耐受性和更好的临床疗效的药物， 安全性比目前可用的治疗方案。为此，我们现在 我提出了两项临床试验，一项针对SLE的认知障碍，另一项针对青少年 类风湿关节炎我们建议“重新利用”一种安全、广泛使用的血管紧张素 用于治疗认知障碍的穿过血脑屏障的抑制剂， 影响了很多SLE患者。在实验室中，这种药物已被证明可以减少 小胶质细胞引起的神经元损伤。我们将使用复杂的脑成像技术来评估 对SLE患者的影响。我们提出的第二项研究是利用“生物电子”医学， 减少JIA（幼年特发性关节炎）儿童关节炎。我们将启动 胆碱能抗炎通路通过刺激迷走神经与非侵入性，非 疼痛的轻微电流。在实验室中，刺激迷走神经可以减少 产生炎性细胞因子。两项研究均旨在评估疗效和安全性， 两者都伴随着综合机制研究，以了解更多关于生物学的信息， 干预的效果。每一个都被设计用于识别潜在的反应生物标志物。 该中心将继续努力开展合作创新临床试验， 通过控制炎症性疾病和减少 器官损伤和功能障碍，2）导致更好地了解的发病机制， 自身免疫性疾病和机制的治疗反应，3）导致个性化的 治疗自身免疫性疾病的药物方法4）评估不会引起 具有临床意义的免疫抑制和5）开展合作创新临床试验 这是制药业不会追求的。

Project Summary/Abstract Despite advances and treatments in autoimmune disease, there remains an unmet need for safer and more effective therapies that are tailored to the individual patient. These advances cannot occur without significant advances in our knowledge and understanding of disease mechanisms. With support from the Autoimmunity Centers of Excellence, we assembled a consortium of outstanding collaborating sites 5 years ago to form “The Feinstein Institute for Medical Research Center for Clinical Research in Autoimmune Disease”. The overarching theme of our Center is that tissue injury occurring in autoimmune disease is often the end-result of multiple and often redundant inflammatory pathways and mediators (cytokines). We continue to believe that an anti-inflammatory approach that modulates multiple inflammatory mediators will be associated with greater clinical efficacy and we will seek agents with improved tolerability and a better safety profile than therapeutic options that are currently available. Towards this end, we now propose two clinical trials, one targeting cognitive impairment in SLE and the other in Juvenile Rheumatoid Arthritis. We are proposing to “repurpose” a safe, widely available angiotensin inhibitor that crosses the blood-brain-barrier for treatment of the cognitive impairment that affects so many patients with SLE. In the laboratory, this medication has been shown to reduce neuronal injury by microglia. We will use sophisticated brain imaging techniques to evaluate the effects in patients with SLE. The second study we propose is to use “bioelectronic" medicine to reduce arthritis in children with JIA (juvenile idiopathic arthritis). We will activate the cholinergic anti-inflammatory pathway by stimulating the vagus nerve with a non-invasive, non- painful mild electric current. In the laboratory, stimulating the vagus nerve reduces the production of inflammatory cytokines. Both studies are designed to evaluate efficacy and safety, and both are accompanied by integrated mechanistic studies to learn more about the biologic effects of the intervention. Each is also designed to identify potential biomarkers of response. This Center will continue to strive to conduct collaborative innovative clinical trials that will 1) promote improved patient outcomes through control of inflammatory disease and a reduction of organ damage and dysfunction, 2) result in a better understanding of the pathogenesis of autoimmune diseases and mechanisms for therapeutic responses, 3) lead to a personalized medicine approach to treatment of autoimmune disease 4) evaluate agents that do not cause clinically significant immunosuppresion and 5) conduct collaborative innovative clinical trials that would not be pursued by the pharmaceutical industry.