Recombinant human defensin for management of ileal Crohn's disease

DESCRIPTION (provided by applicant): Inflammatory bowel disease (IBD), including Crohn's disease, is a chronic inflammation of the intestine, for which current therapies are inadequate. In industrialized countries, Crohn's disease affects about 1 in 500 individuals, and it is estimated that about one million Americans suffer from some form of IBD. Current hypotheses suggest that in the pathogenesis of all forms of IBD, intestinal microbes trigger inflammatory disease in genetically susceptible individuals. Over the past decade, epithelial cells of the intestine, and other tissues, have been identified as a source of defensins and other antimicrobial peptides. These molecules contribute to innate host defense of epithelial surfaces. One antimicrobial peptide expressed by epithelial cells of the human small intestine, human defensin-5 (HD5), is the prime focus of experiments in this grant proposal. Recent investigations provide strong evidence that deficient expression of HD5 is a predisposing factor for Crohn's disease of the ileum. Human defensins are currently not available commercially. Our aims seek to use a protein expression system, ExpressTec, which has been developed by Ventria Bioscience, to produce HD5 using cereal grains. Our proposed studies will yield a commercial source of HD5 that could be used to augment the deficient levels of this molecule in the intestine of ileal Crohn's disease patients. Thus, our efforts may result in a novel therapeutic strategy for the treatment of IBD,