Scientific Abstract

Proposal No.   IBD-0099R
Principal Investigator:  Christoph Hanski, Ph.D.
Applicant Organization:   Charité Universitätsmedizin Berlin, Campus Benjamin Franklin (Germany)
Project Title:  Effects of deoxycholic acid and ursodeoxycholic acid on the development of carcinomas during chronic ulcerative colitis:  proof of principle in an animal model
Period of Award:  March 1, 2004 – June 30, 2006

Patients with chronic ulcerative colitis have a 10-20-fold higher risk of developing colorectal cancer than the general population.  The risk depends on the extent and the duration of the disease.  Preventive measures are urgently needed in order to decrease the incidence of colorectal cancer in inflammatory bowel disease (IBD).  Recent retrospective studies on patients with primary sclerosing cholangitis (PSC) associated with ulcerative colitis indicate that the standard treatment of PSC with ursodeoxycholic acid (UDCA) contributes to the decrease of the risk of developing colon carcinoma.  One of the hypothetical mechanisms of UDCA action is the reduction of the proportion of the luminal deoxycholic acid, which is thought to have a procarcinogenic effect.  Whether UDCA exerts a similar effect in patients with ulcerative colitis is not known at present.

The aim of present proposal is to investigate the effect of ursodeoxycholic acid and deoxycholic acid on the colon carcinoma development in the mouse model of ulcerative colitis.  If this novel animal model confirms the preventive effects of UDCA observed in patients with UC and PSC, it will allow us to investigate in detail the preventive mechanism of UDCA and of its target molecules.  Since UDCA is an approved drug with little side effects, it would facilitate an innovative application of this medication that may lead to the development of a new preventive therapy and the avoidance of some colectomies.