IBD, which is an umbrella term for ulcerative colitis and Crohn disease, is a serious and chronic illness that is thought to affect up to 1 million people in the US alone. Associated with severe abdominal pain and bouts of diarrhea, IBD is seriously debilitating, and furthermore it can contribute to an increased risk of bowel cancer. 

Therapies have traditionally focussed on NSAIDS and steroids as well as a number of immunoregulatory molecules. Clinical control is still however sub-optimal and IBD frequently flares up with such severity that surgery is required. Tumor necrosis factor-alpha (TNF-alpha), is one cytokine that appears to play a crucial role in several disease states, including inflammatory bowel disease. Since the biological activity of TNF-alpha is dependent on the activation of mitogen-activated protein kinases, it is possible that inhibitors of these enzymes could be beneficial in the treatment of inflammatory bowel disease. 

Field-leading researchers at the University of Amsterdam have tested this hypothesis using the JNK and p38 MAPK inhibitor, CNI-1493. Biopsies were taken from patients with severe Crohn's disease treated with this inhibitor. Enhanced TNF-alpha production and JNK and p38 MAPK activation was significantly reduced by pretreatment with CNI-1493. This coincided with clinical benefit and rapid endoscopic ulcer healing. A clinical response was seen in 67% of patients and remission in 42%. Steroids were tapered in 89% of patients. Infliximab has recently entered the market for the treatment of Crohn's disease and it's ability to neutralize TNF-alpha and it's subsequent clinical activity even in patients with fistulas has provided real hope to patients. However some patients still require surgery for fistulas and some display adverse effects and therefore improved blockers of TNF-alpha are required. It is therefore of interest that CNI-1493 was free of adverse effects, a response was seen in 3 of 6 infliximab failures and fistulae healing occurred in 4 of 5 patients. In this respect, molecules such as CNI-1493 deserve real attention as possible alternatives to Infliximab.