Rosiglitazone is a widely used drug in the treatment of patients with diabetes. It is given in capsule or gel form and thus acts throughout the organism by fixing on the PPARg protein; Over the last ten years, it has been demonstrated that PPARg is highly expressed in the colon and is capable of blocking inflammation. In 2003, a group in Lille showed that colon cells of patients with UC had lost the major part of their PPARg. Various studies tested the efficacy of oral treatment with rosiglitazone in UC, with encouraging results. The interest in rosiglitazone was tempered, however, by the discovery of its cardiac toxicity.

A Danish study to be published in the American Journal of Gastroenterology initially confirmed this defect of PPARg in colon cells of patients with UC. Pedersen et al. next demonstrated ex vivo that treatment with rosiglitazone corrected the PPARg defect. That team of Danish physicians, on a small cohort of patients with UC, compared the efficacy of experimental rosiglitazone enema, thereby avoiding secondary cardiac effects as compared to the reference treatment, i.e. mesalazine given by enema for 14 days. Rosiglitazone showed identical efficacy to mesalazine, with a decrease of 50 percent of the clinical score (Mayo score).

These results launched new interest in rosiglitazone in treating chronic inflammatory diseases of the intestines (IBD). The development of new therapies consisting of local administration (topical) of rosiglitazone or any other molecule capable of activating PPARg is creating new hope in the treatment of IBD in general, and of UC in particular.

Reference:

Pedersen G, Brynskov J. Topical Rosiglitazone Treatment Improves Ulcerative Colitis by Restoring Peroxisome Proliferator-Activated Receptor-gamma Activity. Am J Gastroenterol. 2010 Jan 19. [Epub ahead of print]