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治疗药物，用于预防或延迟高风险（表现出胰岛素、GAD 65、IA-2和ZnT自身抗体的人）的糖尿病前期患者发生糖尿病。8）发展为1型糖尿病（T1 D）。该治疗剂旨在使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细胞亚群。本申报资料中涵盖的工作基于体外细胞培养和体内啮齿动物模型获得的初步结果。在进入临床前开发之前， 然而，Akston试图在NOD Tg小鼠的一个月研究中确定最佳治疗方案，随后在野生型NOD小鼠中进行更广泛的八个月研究，以证明在治疗动物中统计学上显著预防糖尿病。这样做将提供关键的 “概念验证”数据，并将导致详细的临床前，IND使安全性和有效性的工作，并最终，临床试验的治疗在人。 这个项目的结果可能是重要的。T1 D患者的直接医疗保健费用目前每年约为200亿美元。除了目前患有T1 D的300万美国人之外，每年还诊断出30，000名新的T1 D患者，在过去十年中，新诊断的20岁以下患者的比例增加了23%。如果成功的话，Akston的治疗可能会导致医疗保健成本的显着降低，并可能使T1 D前儿童和青少年免于终生的葡萄糖监测和胰岛素注射。