New drug may reduce gluten-induced duodenal mucosal damage in celiac disease: NEJM
A new experimental drug may help reduce gluten-induced duodenal mucosal damage in celiac disease, finds a study published in NEJM;
Celiac disease (CeD) is a common intestinal inflammatory disease that affects about 1% of most wheat consuming populations worldwide. CeD is caused by the ingestion of gluten containing foods, such as wheat, spelt, rye and barley, that activate small intestinal inflammatory T cells.
The only current therapy is the rigorous avoidance of even traces of gluten in the daily diet, which is difficult and a social and psychological burden. It was previously identified the body's own enzyme tissue transglutaminase (TG2) as the CeD autoantigen. Moreover, TG2 drives celiac disease pathogenesis by enzymatically modifying dietary gluten peptides that makes them more immunogenic.With this background,a team of researchers therefore developed an oral small molecule (ZED1227) that specifically inhibits TG2 activity in the intestine.While this should attenuate CeD in patients exposed to dietary gluten, it was unclear if it could prevent gluten induced intestinal inflammation and damage.
Taking a step forward, rescent research published in New England Journal of Medicine has shown that treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease.
In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease.
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