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:
- 金额:$ 29.92万
- 依托单位:
- 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:
- 关键词:Adipose tissueAdverse effectsAffinityAldesleukinAmputationAnimal ModelAnimalsAntidiabetic DrugsAttenuatedBindingBinding SitesBlindnessBloodBlood GlucoseBlood VesselsBody WeightCD8B1 geneCancer ModelCardiovascular DiseasesCellsChimeric ProteinsChronicDiabetes MellitusDiabetic mouseDietDoseEragrostisEscherichia coliExhibitsFamily suidaeFatty acid glycerol estersFructoseGenerationsGoalsHalf-LifeHigh Fat DietHolidaysHospitalizationHumanIL2 geneIL2RA geneIL2RB geneIL2RG geneImmuneImmunomodulatorsImmunotherapyIn VitroInflammationInjection of therapeutic agentInsulinInsulin ResistanceInsulin-Dependent Diabetes MellitusInterleukin-2Investigational New Drug ApplicationKidneyKidney FailureMammalian CellMemoryMetforminModelingMusMutationNatural Killer CellsNon-Insulin-Dependent Diabetes MellitusObese MiceObesityOmentumOverweightPatientsPharmaceutical PreparationsPhasePhenotypePlasmaPrincipal InvestigatorRecombinant ProteinsRegulatory T-LymphocyteRenal carcinomaSafetySerum AlbuminSmall Business Innovation Research GrantSyndromeT memory cellTherapeuticToxic effectValidationVisceralWeight GainWeight maintenance regimenWorkabdominal fatabstractingbaseblood glucose regulationcytokinedb/db mousedesigndiabeticeosinophilfeedingglucose toleranceglycemic controlimmunogenicimprovedinnovationinsulin sensitivitymelanomamolecular sizemouse modelnovelnovel strategiesnovel therapeuticspreventprogramspublic health relevancereceptorrestorationsuccess
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.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RIDONG CHEN其他文献
RIDONG CHEN的其他文献
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