Recombinant human defensin for management of ileal Crohn's disease

描述（由申请人提供）：炎症性肠病（IBD），包括克罗恩病，是一种慢性肠道炎症，目前的治疗方法不足。在工业化国家，每500个人中就有1个人患有克罗恩病，据估计，大约有100万美国人患有某种形式的炎症性肠病。目前的假设表明，在所有形式的IBD的发病机制中，肠道微生物在遗传易感个体中引发炎症性疾病。在过去的十年中，肠上皮细胞和其他组织已被确定为防御素和其他抗菌肽的来源。这些分子有助于宿主对上皮表面的先天防御。由人小肠上皮细胞表达的1种抗菌肽，人防御素-5 (HD5)，是本拨款提案中实验的主要焦点。最近的研究提供了强有力的证据，表明HD5表达不足是回肠克罗恩病的一个易感因素。人体防御剂目前还没有商业化。我们的目标是利用Ventria Bioscience开发的蛋白质表达系统ExpressTec，利用谷物生产HD5。我们提出的研究将产生HD5的商业来源，可用于增加回肠克罗恩病患者肠道中该分子的缺乏水平。因此，我们的努力可能会导致一种新的治疗IBD的治疗策略。

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 1 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. 1 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.