APT THERAPEUTICS, INC. — Department of Health and Human Services SBIR Phase I: 400

Description

Diabetic nephropathy DN is one of the most common microvascular complications of diabetes and the leading cause of end stage renal disease in Western and Asian countries The current medical management of diabetes to prevent its complications include tight glycemic control and strict management of blood pressure these established treatments delay the onset and the progression of DN however they have little effect on reversing the progression of DN Hence novel therapies are needed to safely target the other underlying pathophysiological mechanisms and halt or reverse DN Interleukin IL is the key cytokine for the generation survival and function of Treg by direct binding to its high affinity receptor It has been shown that treatment with low dose cancer model dose rIL increased anti inflammatory Treg cells and M type macrophage and inhibited pathogenic interferon secreting T helper type cells in the abdominal fat that led to improvement of glucose tolerance and insulin sensitivity of mice on high fat diet Hence restoration of VAT Treg cells with low dose IL may offer a novel strategy for prevention and treatment of T D and its associated diabeticnephropathy However several drawbacks exist for current low dose rIL therapy including a short half life propensity to in vitro aggregation causing adverse local reaction at injection sites and potentially narrow therapeutic window We have designed a proprietary IL based therapy that will enable selective stimulation of Tregs with an extended half life minimal in vitro aggregation and broad therapeutic window In the proposed Phase I SBIR study we will evaluate the dose response of the drug candidate in the db db murine model of DN Specific Aim To determine whether weekly treatment with mAPT s c halts or reverses DN progression in the db db diabetic model of mice undergoing uninephrectomy without significant side effects The long term goal is to develop the drug candidate as a safe and effective therapy to halt or reverse DN We will determine whether induction of regulatory T cells with an optimized IL analog will abrogate type diabetic nephropathy without behavioral side effects in well established animal models