Final Progress Report

Proposal No.  IBD-0165R
Principal Investigator:  Efi G. Kokkotou, M.D., Ph.D.
Applicant Organization:  Beth Israel Deaconess Medical Center (Boston, Massachusetts, U.S.A.)
Project Title:  Targeting melanin concentrating hormone as a novel treatment for inflammatory bowel disease
Period of Award:  January 1, 2006 – December 31, 2007

Lay summary of Final Progress Report

How the neuroendocrine system modulates intestinal motility and inflammation in IBD, via centrally or locally released hormones and neuropeptides, remains an open question in the area of IBD research. The significance of such pathways in IBD is underscored by the potential association between stress and episodes of disease “flares”. We have identified MCH, a previously described neuropeptide in brain that regulates appetite and energy balance, as a critical player in IBD pathogenesis, by virtue of attenuated development of experimental colitis in mice genetically deficient for MCH. The clinical relevance of MCH in IBD was further highlighted by our finding of increased MCH and MCH receptor expression by various cell types in the inflamed mucosa of patients with IBD, and in particular in the more severe cases. Our studies also suggested targeting MCH as a viable approach to treat mouse experimental colitis and potentially IBD, based on our successful disease attenuation by using an antibody against MCH or an MCH-receptor selective antagonist. Antibody-based biological therapies in IBD, such as anti-TNFalpha;, have recently gained popularity and thus it is quite possible that antibodies against MCH will become an equally effective treatment for IBD, but without the deleterious effects of immunosuppression concomitant to the current biological therapies.  Alternatively, compounds that block the action of MCH by interfering with its receptor binding could be used for treating IBD, alone or in combination with more traditional therapies. More than 96 such MCH-related compounds, designed as anti-obesity remedies, have been developed by the pharmaceutical companies.