MicroRNA-based Diagnostic Testing and Therapies for Inflammatory Bowel Disease
Ulcerative colitis (UC) and Crohn's disease (CD) are the two most common chronic inflammatory bowel diseases (IBD). They often share similar clinical characteristics, such as acute and chronic inflammation of the colon, which makes accurate diagnosis difficult. Studies examining the global gene expression profiles in IBD have shown the increased expression of numerous genes involved in inflammation and fibrosis. Understanding how these inflammatory genes are regulated may lead to the development of advanced therapies targeting several key molecules involved in IBD. Scientists at JHU have discovered that patients with UC have a distinctive microRNA (miRNA) expression pattern in the sigmoid colon, as compared to normal controls. In addition, a miRNA mimic was found to bind and inhibit the expression of MIP-2�a chemotactic cytokine produced by macrophages and intestinal epithelial cells that is upregulated in IBD. These findings have resulted in two inventions: 1) the use of miRNAs as potential biomarkers for IBD disease activity and 2) the use of miRNA mimics as therapies for the treatment of intestinal inflammation. Description (Set) Proposed Use (Set) This invention utilizes miRNA profiles to distinguish the subtypes of IBD. Furthermore, this invention is the first to identify specific miRNAs that inhibit epithelial cell-derived inflammatory cytokine expression and provides a means by which specific therapies can be designed that allow for topical treatment (rectal delivery) of miRNA therapies aimed at decreasing intestinal inflammation. While the use of miRNAs as diagnostic tools and therapies have been suggested for the treatment of cancer, these concepts have not been applied to inflammatory disease processes.
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