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Jul 11, 2013
 |  BC Innovations  |  Cover Story

Debugging Crohn's disease

The intestinal flora of patients with Crohn's disease is frequently populated by adherent-invasive Escherichia coli, which cause intestinal inflammation. Although this inflammatory response is typically treated with tumor necrosis factor-lowering therapies, University of Nantes Angers Le Mans researchers have gone right to the source and targeted the bacteria directly with modified mannosides.1 The researchers are planning to assess the compounds in a chronic mouse model for the disease.

CD is caused by a group of infectious bacterial strains that trigger a tumor necrosis factor (TNF)-induced inflammatory response. Patients experience a shift in the composition of their enteric microbiota, called dysbiosis,2,3 that is associated with overexpression of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6; NCA; CD66c).4

CEACAM6 presents oligomannosides on the surface of intestinal epithelial cells. These oligomannosides allow adherent-invasive E. coli (AIEC), which are part of the intestinal microbiome in about 33% of patients with CD, to bind to the cells via a surface adhesion protein called fimbrial adhesin (fimH).

Marketed CD drugs suppress the inflammatory response by lowering TNF levels. The three anti-TNF antibodies on the market for CD are Humira adalimumab from AbbVie Inc., Remicade infliximab from Johnson & Johnson and Cimzia certolizumab pegol from UCB Group.

Recent data have shown that about 60% of patients responded to Humira, and of those, only 25% remained in remission after 1 year.5

A team led by Sébastien Gouin, research investigator at the Centre National de la Recherche...

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