IMMUNOTHERAPY TRIAL FOR NEW ONSET TYPE 1 DIABETES

新发 1 型糖尿病的免疫治疗试验

• 批准号: 7719503
• 负责人: PETER A GOTTLIEB
• 金额: $ 0.04万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719503
• 关键词: Adverse effects; Antibodies; Atypical lymphocyte; Autoimmune Diseases; Autoimmunity; Beta Cell; Biological Preservation; C-Peptide; Cell Death; Cells; Chronic; Computer Retrieval of Information on Scientific Projects Database; Cyclosporine; Cyclosporins; Daclizumab; Diagnosis; Effectiveness; Funding; Grant; Human; IL2 gene; Immune system; Immunosuppression; Immunosuppressive Agents; Immunotherapy; Institution; Insulin-Dependent Diabetes Mellitus; Interleukin 2 Receptor; Interleukin-2; Intervention; Islet Cell; Islets of Langerhans; Numbers; Patients; Rate; Research; Research Personnel; Resources; Rest; Source; T memory cell; T-Lymphocyte; Therapeutic immunosuppression; Transplantation; United States National Institutes of Health; Work; base; islet; mycophenolate mofetil; nephrotoxicity; type I diabetic

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 1 diabetes in humans is a chronic, slowly progressive autoimmune disease for which immunosuppressive treatments are being explored. Stiller and colleagues [1] first showed that Cyclosporine maintained C-peptide at 1 year from diagnosis in new onset patients but nephrotoxicity limited its use. Our choice of Mycophenolate mofetil (MMF) and Daclizumab, anti-IL2 Receptor antibody, for interventions in new onset type 1 diabetes is based on their effectiveness for transplants and autoimmunity. We predict that MMF, alone or in combination with anti-IL2R antibody, will cause activation-induced cell death of self-reactive lymphocytes. If correct, the hypothesis predicts that MMF will halt islet cell destruction in type 1 diabetes. The anti-IL2R antibody is particularly effective in arresting rejection episodes - presumably through starving activated T cells of IL2. Since type 1 diabetic subjects have an increased number of activated T cells, we hypothesize that the anti-IL2 Receptor antibody will target these potentially autoreactive cells while sparing the resting na¿ve and memory T cells. We predict meaningful preservation of islet function with minimal immune system side effects over the 4-year course of this study. We have powered our study from previous work defining the rate of beta cell loss in the absence of immunosuppression. Our approach is predicated on the view that an immunosuppressive intervention has to reduce the loss of islet cells to < 50% of control over 2 years to have potential usefulness.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 人类中的1型糖尿病是一种慢性，缓慢进行的自身免疫性疾病，正在探索免疫抑制治疗。 Stiller及其同事[1]首先表明，环孢霉素在新发作患者的诊断中维持C肽1年，但肾毒性限制了其使用。我们选择的霉酚酸酯（MMF）和Daclizumab，抗IL2受体抗体，用于新发作1型糖尿病的干预措施是基于它们的移植和自身免疫性的有效性。我们预测，单独或与抗IL2R抗体结合的MMF会导致激活诱导的自反应性淋巴细胞的细胞死亡。如果正确，则假设MMF会停止1型糖尿病中的胰岛细胞破坏。抗IL2R抗体在阻止排斥发作方面特别有效 - 大概是通过IL2的饥饿活化的T细胞。由于1型糖尿病受试者的活化T细胞数量增加，因此我们假设抗IL2受体抗体将靶向这些潜在的自身反应性细胞，同时保留静止的NA¿VE和记忆T细胞。在本研究的4年过程中，我们预测有意义的胰岛功能具有最小的免疫抑制系统副作用。我们已经从以前的工作中为我们的研究提供了动力，该研究在没有免疫抑制的情况下定义了β细胞损失率。我们的方法预测，免疫抑制干预必须在2年内将胰岛细胞的损失降低到<50％的控制，以具有潜在的有用性。