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Novel Nontoxic Therapeutic Interventions for Autoimmune Inflammatory Disease

自身免疫性炎症疾病的新型无毒治疗干预措施

基本信息

批准号：
9916702
负责人：
Cynthia Aranow
金额：
$ 8.38万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9916702
关键词：
Affect Angiotensin-Converting Enzyme Inhibitors Angiotensins Anti-Cholinergics Anti-Inflammatory Agents Arthritis Autoimmune Diseases Autoimmune Process Autoimmune Responses Autoimmunity Biological Biological Markers Blood - brain barrier anatomy Brain imaging Child Chronic Childhood Arthritis Clinical Clinical Research Clinical Trials Conduct Clinical Trials Controlled Clinical Trials Development Disease Dissection Drug Industry Economic Burden Enrollment Functional disorder Genetic Goals Health Homeostasis Image Imaging Techniques Immune Immune response Immunosuppression Impaired cognition Incidence Individual Inflammation Inflammation Mediators Inflammatory Institutes Intervention Knowledge Laboratories Lead Learning Lupus Nephritis Mediator of activation protein Medical Research Medicine Microglia Molecular Neuronal Injury Organ Outcome Painless Pathogenesis Pathogenicity Pathway interactions Patient-Focused Outcomes Patients Pharmaceutical Preparations Prevalence Production Research Safety Site Systemic Lupus Erythematosus Therapeutic Therapeutic Intervention Toxic effect Translations Vagus nerve structure adaptive immune response base blood-brain barrier crossing burden of illness clinical care clinical center clinical efficacy clinically significant cognitive function cytokine design disease heterogeneity effective therapy improved improved outcome individual patient individualized medicine inhibitor/antagonist innovation intervention effect new therapeutic target novel personalized approach personalized medicine potential biomarker predictive marker prognostic programs response response biomarker tissue injury tool treatment response vagus nerve stimulation

项目摘要

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.

项目总结/文摘