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: 8843352
• 负责人: Cynthia Aranow
• 金额: $ 8.43万
• 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/8843352
• 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; 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; individualized medicine; innovation; intervention effect; mortality; new therapeutic target; novel; personalized medicine; 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. RELEVANCE: There is still an unmet need for safer and more efficacious treatments for patients with autoimmune diseases. We propose to study therapies that modulate multiple inflammatory pathways which may be more efficacious and safer than current options. We are proposing a collaborative Center to conduct clinical trials accompanied by mechanistic studies to study such agents and advance our understanding of 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步，但对于针对个体患者量身定制的更安全、更有效的治疗的需求仍然未得到满足。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是多余的炎症途径和介质（细胞因子）的最终结果；我们相信，调节多种炎症介质的抗炎方法将具有更大的临床疗效。我们将寻找比目前的治疗方案具有更好的耐受性和更好的安全性的药物。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，我们提出了一项 GTS-21 的研究。该药物通过与 α7 烟碱受体结合，激活胆碱能抗炎途径，从而减少炎症细胞因子的产生。第二项试验是 ajulemic 酸治疗 SLE 的研究。该药物是一种合成大麻素，非精神药物，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功效，并且每项研究都伴随着机制研究，以确定治疗干预的生物学效应。每一项还旨在评估潜在的反应生物标志物。为了完成这些研究，我们组建了一个由优秀合作机构组成的联盟，成立了“范斯坦医学研究中心自身免疫性疾病临床研究中心”。该中心将努力开展合作创新临床试验，1) 通过控制炎症性疾病和减少器官损伤和功能障碍，促进改善患者治疗结果，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) 开发治疗自身免疫性疾病的个性化医疗方法，4) 评估不会引起临床显着影响的药物。 免疫抑制；5）开展制药行业不会进行的协作创新临床试验。 相关性：自身免疫性疾病患者对更安全、更有效的治疗的需求仍未得到满足。我们建议研究调节多种炎症途径的疗法，这可能比目前的选择更有效、更安全。我们提议建立一个合作中心来进行临床试验并进行机制研究，以研究此类药物并增进我们对疾病的了解。