Lay Summary

Proposal No. IBD-0005
Principal Investigator:  Robert W. Summers, M.D.
Applicant Organization:  University of Iowa (Iowa City, U.S.A.)
Project Title:  A controlled clinical trial of Trichuris suis in the therapy of active ulcerative colitis
Period of Award:  July 1, 2002 - December 31, 2003

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colon that causes fatigue, diarrhea, bleeding and abdominal pain.  The cause of the Inflammatory Bowel Disease (IBD) remains unknown.  It is thought that both genetic and environmental factors trigger an inflammatory process, which is misdirected and destructive to the lining of the large intestine.  All effective medical treatments act to reduce the inflammatory process.  Unfortunately, many of the drugs are ineffective or have significant side effects or complications.

We propose to use a naturally occurring biological agent that appears to modulate or modify the body’s immune system in a favorable way without side effects or complications.  The agent is an intestinal worm that is a common inhabitant of the pig intestine, Trichuris suis.  It is administered in the form of eggs that open in the intestine, release larvae that temporarily attach to the lining of the intestine.  In the pig, the worms remain attached, mature and produce eggs for several years.  In humans, however, they only attach for a few weeks and are rejected before they can produce eggs.  There is evidence that the worms induce an immune response that reduces or eliminates the inflammation that is so destructive to the lining of the bowel.  The worms have been shown in our laboratory to improve experimental colitis in mice without causing damage to the host.

In less developed countries, hundreds of millions of people are colonized with similar worms (intestinal helminths).  In these areas, there is essentially no IBD.  Conversely, in Western industrialized countries, helminths have been mostly eliminated since the 1930’s.  Meanwhile, IBD frequency has risen concomitantly.  These observations led us to perform an open trial of this therapy in patients with IBD.  Patients with both UC and Crohn's disease (CD) improved, and most went into remission.  Although a single dose of eggs causes only temporary benefit, repeated doses every 2-3 weeks induced prolonged remissions in nearly every patient with no recognizable side effects or complications.  These results have encouraged us to perform a large, randomized, blinded clinical trial in patients with UC.

This new approach to the therapy of IBD could be very useful because of the lack of side effects.  It may also increase our understanding of the basic reasons for the disease and perhaps its therapy and prevention.