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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 人类1型糖尿病是一种慢性、缓慢进展的自身免疫性疾病，正在探索免疫抑制治疗。Stiller及其同事[1]首次表明，环孢素在新发患者中从诊断开始1年时可维持C肽，但肾毒性限制了其使用。 我们选择吗替麦考酚酯（MMF）和抗IL 2受体抗体Daclizumab用于新发1型糖尿病的干预，是基于它们对移植和自身免疫的有效性。我们预测，霉酚酸酯，单独或与抗IL-2 R抗体组合，将导致激活诱导的自身反应性淋巴细胞的细胞死亡。如果正确的话，该假设预测，MMF将停止1型糖尿病的胰岛细胞破坏。抗IL 2 R抗体在阻止排斥反应发作中特别有效-推测是通过使活化的T细胞饥饿IL 2。由于1型糖尿病患者的活化T细胞数量增加，我们假设抗IL 2受体抗体将靶向这些潜在的自身反应性细胞，同时保留静息幼稚和记忆T细胞。我们预测在这项研究的4年过程中，胰岛功能得到了有意义的保护，免疫系统副作用最小。我们从以前的工作中定义了在没有免疫抑制的情况下β细胞损失的速率，为我们的研究提供了动力。我们的方法是基于这样的观点，即免疫抑制干预必须在2年内将胰岛细胞的损失减少到控制的50%以下才有潜在的有用性。