Lay Summary

Proposal No. IBD-0229
Principal Investigator:  F. Gary Toback,  M.D., Ph.D.
Applicant Organization:  The University of Chicago (Illinois, U.S.A.)
Project Title:  Assessment of therapeutic efficacy of a novel peptide in murine models of human IBD
Period of Award:  April 1, 2008 – February 28, 2011

We recently characterized a new protein made in GI cells, and identified a fragment called AMP peptide that has several biological effects that point to its possible use as a new agent to treat IBD.  In experimentally-injured mouse colon, treatment with AMP peptide reduced ulcer formation in the gut lining, and delays the appearance of bloody diarrhea.  AMP peptide is novel in its ability to facilitate repair of the injured GI tract by acting on “tight junction proteins” that bind cells of the intestinal lining to one another, thereby preventing bacteria and toxins within the gut from crossing into the blood stream.  The therapeutic peptide also stimulates growth and movement of new cells needed to replace those that died, and in this way could repair the injured lining of the colon.  These observations suggest that administration of AMP peptide could stabilize tight junctions between cells in the colon, reseal injuries of the colonic lining, and speed wound healing to restore the structure and function of the injured gut.

The project is focused on validating the clinical efficacy of AMP peptide as a new agent that could be developed to treat IBD in the near future.  The specific aims of this project are to: (1) determine if AMP peptide acts as a therapeutic agent in three mouse models that resemble human IBD more closely than the animal model of colitis studied previously, and (2) find out whether treatment with the peptide affects absorption of various molecules and ions through the intestinal lining.

The results of this project could rationalize rapid development of a new therapeutic agent for patients with IBD that re-seals breaks in the intestinal lining to prevent bacteria and their toxins from inducing bowel wall inflammation, and also speeds healing of the injured colon.