CC-4066 in Acute Pancreatitis

Acute Pancreatitis (AP) is a sudden severe inflammation of the pancreas gland that begins in the pancreatic acinar cells that produce digestive enzymes. Pancreatic necrosis, systemic inflammatory response syndrome, multiple organ failure and sepsis are characteristic of the disease which results in significant mortality and is currently without disease-modifying therapy. The disease is extremely painful requiring hospitalisation of between 5 – 30 days duration. In most cases the disease is caused either by gallstones blocking drainage of the bile duct and exposing the acinar cells to the toxic effects of bile acid or by excessive alcohol consumption. Both factors cause necrosis of acinar cells by either direct toxicity (bile acids) or by amplifying physiological Ca2+ signals leading to necrotic cell death (alcohol).

Prof. Robert Sutton and his group have discovered cyclophilin D as the key orchestrator of the pathophysiology of acute pancreatitis and validated the potential of cyclophilin inhibition using both genetic approaches as well as various small molecule cyclophilin inhibitors (Mukherjee R, Sutton R et al, GUT Sept 24, 2015).