Scientific Abstract

Proposal No.  IBD-0167
Principal Investigator:  Carl D. Kirkwood, Ph.D.
Applicant Organization:  Murdoch Childrens Research Institute (Parkville, Australia)
Project Title:  Does a viral agent induce Crohn's disease?  A search for viral agent(s) in children with early onset Crohn's disease
Period of Award:  November 1, 2005 – April 30, 2009

Crohn’s disease is a chronic inflammation occurring anywhere in the gastrointestinal tract.  Onset of symptoms usually occurs in adolescence or early adulthood.  Treatment involves long-term use of immunosuppressive medication to relieve symptoms and preserve mucosal integrity.  However, treatment sometimes is ineffective and progression of inflammatory changes may require surgery.

Over the past 20 years, the incidence of Crohn’s disease has increased markedly in developed countries.  An environmental cause or trigger appears likely, but its nature is unknown.  The observed increased incidence of Crohn’s disease could be due to an infectious agent or agents.  It is possible that more than one etiologic agent is involved, analogous to the multiple agents isolated from children with gastroenteritis.  Many different infectious agents have been implicated in Crohn’s disease.  Interpretation of research results has been inconclusive, perhaps because almost all studies have examined adult patients with chronic disease, many of whom have been receiving immunosuppressive agents and other medications capable of altering gut flora.

This proposal is a pilot study designed to test the hypothesis that Crohn’s disease is initiated in genetically susceptible individuals by a viral agent capable of causing persistent immune mediated tissue injury.  We propose to apply cutting edge molecular biological techniques to search for viral agents at the site of Crohn’s disease lesions in children undergoing initial endoscopic examination prior to use of medication.  Biopsy tissue, circulating peripheral blood mononuclear cells and gut macrophages will be examined by RNA and DNA based molecular technologies capable of identification of known and unknown viral infectious agents.  Our approach mimics the successful Australian strategies that have previously identified rotavirus and Helicobacter pylori at the sites of gastrointestinal tract lesions.