Lay Summary
Proposal No. IBD-0038
Principal Investigator: Torsten Kucharzik, M.D.
Applicant Organization: University of Münster (Germany)
Project Title: Role of alpha-MSH and related tripeptides as potential anti-inflammatory agents during inflammatory bowel disease
Period of Award: January 1, 2003 – December 31, 2004
The etiology and pathogenesis of chronic inflammatory bowel disease including Crohn’s disease and ulcerative colitis remains obscure. As the pathogenesis of these diseases is only partially understood, the treatment is based on broad-spectrum anti-inflammatory agents such as steroids. Because of a variety of side effects and a high percentage of treatment failure, the development of more specifically acting anti-inflammatory agents is necessary.
In our study, we will evaluate alpha-melanocyte-stimulating-hormone (α-MSH) regarding its potential use as an anti-inflammatory agent for treatment of IBD. Α-MSH is an endogenous peptide that has been shown to have potent anti-inflammatory properties in a variety of animal disease models as well as in cell culture experiments. It is currently evaluated as a drug that may be used for various human diseases. Preliminary results have shown promising effects during cutaneous inflammation in humans. Recent data suggest that smaller peptides that are derived from α-MSH have the same anti-inflammatory properties as α-MSH. The advantage of these smaller peptides may be that they are cheaper, more stable and may have fewer side effects. From the current data, we believe that α-MSH and its related peptides have strong anti-inflammatory properties and may be useful as agents for treatment of patients with chronic active IBD. Systemic treatment for chronic active IBD as well as topic treatment during left sided ulcerative colitis may be a useful therapeutic approach in the near future. From the current data, no side effects have been reported so far.
To evaluate this agent, we intend to perform studies in different animal models of IBD. To learn more about the mechanisms of how α-MSH and its smaller peptides are acting, we also want to perform cell culture experiments with intestinal epithelial cells, a cell type that is known to be relevant for the inflammatory process of IBD and verify results on human intestinal tissue from IBD patients.
From the results, we hope to receive information whether α-MSH, and in particular its smaller peptide KPV, may be useful as a potential agent for treatment of IBD. If it turns out that α-MSH is a potent anti-inflammatory drug in animal models of IBD, we will perform further studies in human IBD in the near future.