IL2-based Immunotherapy for Type 2 Diabetes

DESCRIPTION provided by applicant Principal Investigator Program Director Last First Middle Chen Ridong Abstract Type diabetes T D is a leading cause of cardiovascular disease renal failure blindness amputations and hospitalization Up to of T D patients are overweight or obese which induces chronic low grade inflammation of adipose tissue and promotes insulin resistance and T D 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 CD CD Foxp 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 IL 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 IL may offer a novel strategy for mitigating obesity related low grade inflammation and reversing insulin resistance and T D We have designed an IL based therapy that will enable selective stimulation of Tregs In the proposed Phase I SBIR study we will determine whether weekly treatment for weeks leads to improvement of insulin sensitivity and glucose control while reducing excessive body weight gain in the T D 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 T D alone or in combination with current therapies to improve glucose homeostasis and attenuate diabetes associated complications while simultaneously reducing excessive body weight gain PUBLIC HEALTH RELEVANCE The proposed approach involves the treatment of Type Diabetes Mellitus with weekly dosing of a novel immunomodulator in order to attenuate obesity induced low grade inflammation improve glucose control and reduce excessive body weight gain