Proposal for The Feinstein Center for Clinical Research in Autoimmune Disease

描述（由申请人提供）：尽管自身免疫性疾病的治疗取得了进展，但对针对个体患者的更安全、更有效的治疗方法的需求仍未得到满足。如果我们对疾病机制的认识和理解没有重大进展，这些进步就不可能发生。我们提出的计划的总体主题是，由于自身免疫性疾病中发生的组织损伤是多种且经常冗余的炎症途径和介质（细胞因子）的最终结果；我们相信，一种调节多种炎症介质的抗炎方法将与更大的临床疗效相关。我们将寻找比目前的治疗方案耐受性更好、安全性更好的药物。为此，我们提出两项临床试验，一项针对RA，另一项针对SLE。在RA中，我们建议对GTS-21进行研究。这种药物通过参与α - 7尼古丁受体激活胆碱能抗炎途径，导致炎症细胞因子的产生减少。第二个试验是研究阿菊酸在SLE中的作用。本品是一种合成的非精神类大麻素，具有多种抗炎特性。每一项研究都将评估所研究药物的功效，每一项研究都伴随着机制研究，以确定治疗干预的生物学效应。每一种都被设计用来评估潜在的生物标志物。为了完成这些研究，我们组建了一个由优秀合作站点组成的联盟，成立了“范士丹自身免疫性疾病临床研究医学研究中心”。本中心将努力开展协作性创新临床试验，以期1)通过控制炎症性疾病和减少器官损伤和功能障碍来改善患者的预后，2)更好地了解自身免疫性疾病的发病机制和治疗反应机制。3)引领治疗自身免疫性疾病的个性化医学方法4)评估不会引起临床显著免疫抑制的药物5)开展制药行业不会追求的协作创新临床试验。

DESCRIPTION (provided by applicant): Despite advances and treatments in autoimmune disease, there remains an unmet need for safer and more efficacious treatments that are tailored to the individual patient. These advances cannot occur without significant advances in our knowledge and understanding of disease mechanisms. The overarching theme of our proposed Program is that since the tissue injury occurring in autoimmune disease is the end result of multiple and often redundant inflammatory pathways and mediators (cytokines); we believe that an anti-inflammatory approach that modulates multiple inflammatory mediators will be associated with greater clinical efficacy. We will seek agents with improved tolerability and a better safety profile than current therapeutic options. Towards this end, we propose two clinical trials, one in RA and the other in SLE. In RA, we propose a study of GTS-21. This agent activates the cholinergic anti-inflammatory pathway by engaging the alpha 7 nicotinic receptor resulting in reduced production of inflammatory cytokines. The second trial is a study of ajulemic acid in SLE. This agent is a synthetic cannaboid which is non psychotropic and which possesses multiple anti-inflammatory properties. Each of these studies will evaluate the efficacy of the studied agent and each is accompanied by mechanistic studies to determine the biologic effects of the therapeutic intervention. Each is also designed to assess potential biomarkers of response. To accomplish these studies, we have assembled a consortium of outstanding collaborating sites to form "The Feinstein Institute for Medical Research Center for Clinical Research in Autoimmune Disease". This Center will 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 immunosuppression and 5) conduct collaborative innovative clinical trials that would not be pursued by the pharmaceutical industry.