Proposal for The Feinstein Center for Clinical Research in Autoimmune Disease

范斯坦自身免疫性疾病临床研究中心提案

• 批准号: 8680575
• 负责人: Cynthia Aranow
• 金额: $ 16.85万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8680575
• 关键词: Anti-Inflammatory Agents; Anti-inflammatory; Autoimmune Diseases; Autoimmune Responses; Autoimmunity; Biological Markers; Clinical Research; Clinical Trials; Conduct Clinical Trials; Controlled Clinical Trials; Development; Disease; Dissection; Drug Industry; Functional disorder; GTS-21; Genetic; Health; Health Care Costs; Homeostasis; Immune; Immune response; Immunosuppression; Incidence; Individual; Inflammation; Inflammation Mediators; Inflammatory; Injury; Institutes; Knowledge; Lead; Mediator of activation protein; Medical Research; Medicine; Morbidity - disease rate; Nicotinic Receptors; Organ; Outcome; Pathogenesis; Pathway interactions; Patients; Prevalence; Production; Property; Rheumatoid Arthritis; Safety; Site; Systemic Lupus Erythematosus; Therapeutic; Therapeutic Intervention; Tissues; Toxic effect; ajulemic acid; cholinergic; clinical efficacy; clinically significant; cytokine; design; improved; innovation; intervention effect; mortality; new therapeutic target; novel; programs; response

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.

描述（由申请人提供）：尽管自身免疫性疾病的进展和治疗，但仍然需要针对个体患者定制的更安全和更有效的治疗。如果我们对疾病机制的认识和理解没有重大进展，这些进展就不可能发生。我们提出的计划的首要主题是，由于自身免疫性疾病中发生的组织损伤是多种且通常冗余的炎症途径和介质（细胞因子）的最终结果;我们认为，调节多种炎症介质的抗炎方法将与更大的临床疗效相关。我们将寻找比目前治疗方案具有更好耐受性和更好安全性的药物。为此，我们提出了两个临床试验，一个在RA和其他系统性红斑狼疮。在RA中，我们提出了GTS-21的研究。该药物通过与α 7烟碱受体结合激活胆碱能抗炎途径，导致炎性细胞因子的产生减少。第二项试验是阿佳酸在SLE中的研究。该药剂是一种合成大麻素，其不具有精神作用，并且具有多种抗炎特性。这些研究中的每一项都将评估所研究药物的疗效，并且每一项都伴随着机制研究，以确定治疗干预的生物学效应。每一项也被设计用于评估潜在的反应生物标志物。为了完成这些研究，我们已经组建了一个由优秀合作研究中心组成的联盟，组成了“Feinstein医学研究所自身免疫疾病临床研究中心”。该中心将致力于开展合作创新临床试验，这些临床试验将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的机制，3）导致治疗自身免疫性疾病的个性化药物方法4）评估不引起临床显著免疫抑制的药剂，以及5）开展制药行业不会追求的合作创新临床试验。