Lay Summary

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

We propose to investigate the role of melanin-concentrating hormone (MCH) in inflammatory bowel disease (IBD).  MCH is a neuropeptide that is produced in the brain and regulates food intake and body weight, thus serving as an important target to treat obesity.  We found that MCH is upregulated in the colon of mice with experimental colitis.  Most importantly, we have shown that mice genetically lacking MCH develop less severe colitis and this response can be reproduced in normal mice after treatment with an antibody against MCH.  These novel observations suggest a proinflammatory role of MCH in IBD pathogenesis. Moreover, these data open the intriguing possibility to treat IBD by blocking the action of MCH.  Several major pharmaceutical companies are currently investigating the use of MCH antagonists as anti-obesity drugs and based on our evidence, these agents can be potentially used to treat IBD.  Studies included in this proposal will address this possibility by examining tissues and serum of IBD patients for the presence of MCH and its relation with disease activity and will further investigate the potential therapeutic role of MCH antagonism using experimental models of colitis relevant to IBD.