Lay Summary

Proposal No. IBD-0188R
Principal Investigator:  Tor C. Savidge, Ph.D.
Applicant Organization:  University of Texas Medical Branch at Galveston (U.S.A.)
Project Title:  To examine the therapeutic potential of a novel mucosal barrier-inducing factor in the treatment of Crohn's disease
Period of Award:  March 1, 2007  – February 29, 2008

Despite extensive research, the etiology of Crohn’s inflammatory bowel disease remains unknown.  A number of clinical studies have demonstrated an increased intestinal permeability in Crohn’s disease patients and in their first-degree relatives.  Enhanced mucosal permeability is also a predictive factor of disease recurrence.  Thus, a primary disorder of intestinal barrier function constitutes a potential factor in the pathogenesis.

We have identified a novel regulator of intestinal barrier function that could restore the primary permeability disorder that is apparent in Crohn’s disease.  We characterized this molecule as a modified form of glutathione, which is an abundant anti-oxidant molecule that protects the intestine against inflammation.  We plan to study whether Crohn’s disease patients lack the ability to regulate the formation of this important molecule, as has been shown in asthma and amyotrophic lateral sclerosis.  If this is indeed the case, then clinical therapy using an oral formulation of this molecule is possible, as is seen in patients with cystic fibrosis.