Lay Summary

Proposal No. IBD-0110
Principal Investigator:  Scott E. Plevy, M.D.
Applicant Organization:  University of Pittsburgh (Pennsylvania, U.S.A.)
Project Title: Clostridium perfringens as a novel therapeutic vehicle in inflammatory bowel disease
Period of Award:  August 1, 2004 - January 31, 2006

Bacteria that normally reside in all of our intestines are known to be important in the initiation and perpetuation of inflammatory bowel disease (IBD).  In fact, IBD may be caused by an abnormal inflammatory reaction against bacteria that in most people constantly exist inside the intestine and do not cause any harm.  Therefore, an exciting area to develop new treatments for IBD is through the characterization or creation of bacteria that may suppress inflammation in the intestine.  One approach has been to genetically engineer harmless intestinal bacteria to express anti-inflammatory proteins.

 In this proposal, we will genetically engineer a normal resident of the intestinal bacterial population, Clostridium perfringens (C. perfringens), to express the anti-inflammatory protein interleukin-10 (IL-10).  C. perfringens is a potentially novel way to treat Crohn’s disease (CD) because it can deliver this anti-inflammatory protein directly to the terminal ileum, which is the area of the intestine most frequently affected in CD.  In addition, by delivering this protein directly to the intestine rather than through the bloodstream, treatment may be more effective and without side effects related to suppressing the immune system throughout the entire body.  We will perform experiments to create these genetically engineered bacteria and we will test whether this is an effective treatment for IBD in two different mouse models of IBD.  Each of these mice develops an IBD that has similarities to human CD.  If these experiments are successful, C. perfringens may be tested in humans as to their safety and efficacy in treating IBD.