A2a Adenosine Agonists for Diabetic Nephropathy

DESCRIPTION (provided by applicant): Diabetic nephropathy (DN) accounts for approximately 40% of the cases of renal failure requiring dialysis or transplantation. Moreover, diabetic nephropathy is associated with markedly higher morbidity and mortality rates. It is important to develop novel interventions to prevent complications of diabetes. Inflammation in the genesis of diabetes, as well as its complications, is considered an important pathogenic mechanism. Adenosine 2A receptors (A2ARs) are expressed in kidney as well as bone marrow derived cells and we have previously shown that upon activation A2A Rs reduces inflammation when administered acutely. Our preliminary data demonstrate that A2A R agonists have profound effects to reduce renal injury when infused chronically in a rat model of streptozotocin (STZ)-induced diabetic nephropathy. Adenosine Therapeutics, LLC has recently developed ATL313, a novel, orally active A2A R agonist. The 1st Aim of this Phase 1 application is to examine the pharmacokinetics, oral bioavailability and initial toxicology of ATL313. The 2nd Aim is to demonstrate the proof of principle that ATL313 is effective in primary and secondary prevention of diabetic nephropathy. ATL313 will be administered via osmotic mini-pumps to establish its efficacy. This will prepare us for the Phase 2 goal of further testing of the compound through oral administration.