Selective Removal of Insulin-Specific B-cells to Prevent Type I Diabetes in NOD Mice

选择性去除胰岛素特异性 B 细胞以预防 NOD 小鼠的 I 型糖尿病

• 批准号: 8981050
• 负责人: TODD C ZION
• 金额: $ 24.98万
• 依托单位: AKSTON BIOSCIENCES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8981050
• 关键词: 20 year old; Accounting; Adipocytes; Affect; Affinity; Age; Alveolar Macrophages; American; Animals; Autoantibodies; Autoantigens; Autoimmune Diabetes; Autoimmune Diseases; Autoimmune Process; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Beta Cell; Binding; Blood Glucose; Cell Culture Techniques; Cells; Chemicals; Child; Clinical; Clinical Trials; Coculture Techniques; Data; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diet; Disease; Dose; Economics; Emotional; Ensure; Excision; Female; Glucose; Health Care Costs; Human; In Vitro; Inbred NOD Mice; Injection of therapeutic agent; Insulin; Insulin Receptor; Insulin-Dependent Diabetes Mellitus; Intellectual Property; Intervention; Investigational Drugs; Knowledge; Lead; Life; Longevity; Measurement; Mediating; Medical; Mus; Muscle Cells; Newly Diagnosed; PTPRC gene; Pain; Patients; Play; Positioning Attribute; Process; Property; Public Health; Rattus; Regimen; Risk; Rodent Model; Role; Safety; Saline; Site; Solutions; Staging; T-Lymphocyte; Techniques; Teenagers; Testing; Therapeutic; Time; Treatment Protocols; Universities; Work; age group; base; design; diabetic; diabetic patient; dosage; experience; glucose monitor; glycemic control; glycosylated insulin; high risk; in vivo; islet; killings; macrophage; man; mannose receptor; mouse model; pre-clinical; prevent; programs; psychologic; public health relevance; research clinical testing; treatment duration

 DESCRIPTION (provided by applicant): Akston Biosciences Corp. is developing a subcutaneously administered therapeutic for preventing or delaying the onset of diabetes in pre-diabetic patients who are at high risk (those who display autoantibodies for insulin, GAD65, IA-2, and ZnT8) for developing Type 1 diabetes (T1D). The therapeutic is designed to delete a subset of B-cells that likely play a role in disease development using a patient's own macrophages. The work covered in this submission builds on preliminary results obtained from both in vitro cell culture and in vivo rodent models. Before entering into preclinical development, however, Akston seeks to identify the best therapeutic regimen in a one month study in NOD Tg mice, followed by a more extensive eight month study in wild-type NOD mice to demonstrate statistically significant prevention of diabetes in treated animals. Doing so will provide critical "proof-of-concept" data and will lead to detailed preclinical, IND-enabling safety and efficacy work and, eventually, clinical testing of the therapeutic in man. The impacts to public health as a result of this project are potentially significant. Healthcare costs directly attributable to T1D patients currently account for nearly $20 billion annually. In addition to the 3 million Americans who currently live with T1D, 30,000 new T1D patients are diagnosed each year, with the rate of newly diagnosed patients < 20 years of age increasing by 23% in just the past decade. If successful, Akston's therapeutic could lead to a significant reduction in health care costs and possibly free pre-T1D children and teenagers from a lifetime of glucose monitoring and insulin injections.

 描述（由申请人提供）：Akston Biosciences Corp. 正在开发一种皮下给药疗法，用于预防或延缓 1 型糖尿病 (T1D) 高危糖尿病前期患者（表现出胰岛素、GAD65、IA-2 和 ZnT8 自身抗体的患者）糖尿病的发病。该疗法旨在利用患者自身的巨噬细胞删除可能在疾病发展中发挥作用的 B 细胞子集。本提交内容涵盖的工作建立在体外细胞培养和体内啮齿动物模型获得的初步结果的基础上。在进入临床前开发之前， 然而，Akston 试图通过对 NOD Tg 小鼠进行为期一个月的研究来确定最佳治疗方案，随后对野生型 NOD 小鼠进行更广泛的八个月研究，以证明在治疗动物中具有统计学意义的糖尿病预防作用。这样做将提供关键 “概念验证”数据，并将导致详细的临床前、支持 IND 的安全性和有效性工作，并最终进行人体治疗的临床测试。对公众健康的影响 该项目的结果可能具有重大意义。目前，T1D 患者直接产生的医疗费用每年接近 200 亿美元。除了目前患有 T1D 的 300 万美国人之外，每年还会诊断出 30,000 名新的 T1D 患者，其中 20 岁以下新诊断患者的比例在过去十年中增加了 23%。如果成功，阿克斯顿的治疗方法可能会显着降低医疗保健成本，并可能使 1 型糖尿病前期儿童和青少年摆脱一生的血糖监测和胰岛素注射。