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IL2-based Immunotherapy for Type 2 Diabetes

基于 IL2 的 2 型糖尿病免疫疗法

基本信息

批准号：
9135661
负责人：
RIDONG CHEN
金额：
$ 29.92万
依托单位：
APT THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9135661
关键词：
Adipose tissue Adverse effects Affinity Aldesleukin Amputation Animal Model Animals Antidiabetic Drugs Attenuated Binding Binding Sites Blindness Blood Blood Glucose Blood Vessels Body Weight CD8B1 gene Cancer Model Cardiovascular Diseases Cells Chimeric Proteins Chronic Diabetes Mellitus Diabetic mouse Diet Dose Eragrostis Escherichia coli Exhibits Family suidae Fatty acid glycerol esters Fructose Generations Goals Half-Life High Fat Diet Holidays Hospitalization Human IL2 gene IL2RA gene IL2RB gene IL2RG gene Immune Immunomodulators Immunotherapy In Vitro Inflammation Injection of therapeutic agent Insulin Insulin Resistance Insulin-Dependent Diabetes Mellitus Interleukin-2 Investigational New Drug Application Kidney Kidney Failure Mammalian Cell Memory Metformin Modeling Mus Mutation Natural Killer Cells Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity Omentum Overweight Patients Pharmaceutical Preparations Phase Phenotype Plasma Principal Investigator Recombinant Proteins Regulatory T-Lymphocyte Renal carcinoma Safety Serum Albumin Small Business Innovation Research Grant Syndrome T memory cell Therapeutic Toxic effect Validation Visceral Weight Gain Weight maintenance regimen Work abdominal fat abstracting base blood glucose regulation cytokine db/db mouse design diabetic eosinophil feeding glucose tolerance glycemic control immunogenic improved innovation insulin sensitivity melanoma molecular size mouse model novel novel strategies novel therapeutics prevent programs public health relevance receptor restoration success

项目摘要

DESCRIPTION (provided by applicant): Principal Investigator/Program Director (Last, First, Middle: Chen, Ridong Abstract Type-2 diabetes (T2D) is a leading cause of cardiovascular disease, renal failure, blindness, amputations and hospitalization. Up to 80% of T2D patients are overweight or obese, which induces chronic, low-grade inflammation of adipose tissue and promotes insulin resistance and T2D. Moreover, weight gain is the common side-effect of older anti-diabetic drugs. Current therapies are not a cure and require daily administration. Hence, novel therapy that improves glucose control while simultaneously reducing body weight is urgently needed. CD4+CD25+Foxp3+ regulatory T cells (Treg) modulate inflammation and insulin resistance. Very interestingly, Treg cells with a unique phenotype are highly enriched in the visceral adipose tissue (VAT) of normal animals, but their numbers are strikingly and specifically reduced in insulin-resistant models of obese animals. Importantly, decreased numbers of Treg are also found in obese human omental. Interleukin-2 (IL-2) is the key cytokine for the generation, survival, and function of Treg by direct binding to its high affinity receptor. Hence, restoration of VAT Treg cells with low-dose IL2 may offer a novel strategy for mitigating obesity related low-grade inflammation and reversing insulin resistance and T2D. We have designed an IL2-based therapy that will enable selective stimulation of Tregs. In the proposed Phase I SBIR study, we will determine whether weekly treatment for 4 weeks leads to improvement of insulin sensitivity and glucose control, while reducing excessive body weight gain in the T2D models of obese db/db mice and diet-induced obese mice. The long-term goal of this project is to develop a novel treatment (weekly or bi-weekly) for T2D, alone or in combination with current therapies, to improve glucose homeostasis and attenuate diabetes-associated complications while simultaneously reducing excessive body weight gain.