Lay Summary

Proposal No. IBD-0171R
Principal Investigator:  Laura P. Hale, M.D., Ph.D.
Applicant Organization:  Duke University (Durham, North Carolina, U.S.A.)
Project Title: Therapy of inflammatory bowel disease using LMP-420
Period of Award:  March 1, 2006 – February 28, 2007

The recent introduction of the tumor necrosis factor (TNF)-inhibiting drug RemicadeTM has revolutionized the treatment of inflammatory bowel disease (IBD), particularly for patients with Crohn’s disease.  However, Remicade also has significant disadvantages: it is expensive, must be injected and can lose effectiveness with time. Patients treated with Remicade may also develop serious or life-threatening infections. LMP-420 is a newly discovered drug that also interferes with the TNF pathway, but works in a different way than Remicade. Our experiments thus far show that LMP-420 prevents production of TNF and several other substances that contribute to colon inflammation. Although most studies done thus far have administered LMP-420 by injection, its properties suggest that it may also be locally active within the intestine if given orally. This could maximize its beneficial effects while minimizing its side effects, particularly in comparison with infliximab.  We believe that treatment with LMP-420 will decrease intestinal inflammation. The aims of this proposal are to determine how LMP-420 affects colon inflammation in two well-established mouse models of IBD.  If the results of this initial study appear promising, a follow-up proposal will be submitted to determine issues related to oral administration as well as the benefits of LMP-420 in a third model of colitis or in treatment of human colon tissues in the laboratory. This unique new drug could represent a major advance in the therapy of patients with IBD. The studies that we propose will also add to our understanding of how effective IBD drugs work, which can lead to development of a variety of improved IBD therapies.