Oral Transglutaminase 2 Inhibitor Beneficial in Celiac Disease

For patients with celiac disease, treatment with a selective oral transglutaminase 2 inhibitor (ZED1227) attenuates gluten-induced duodenal mucosal damage, according to a study published in the July 1 issue of the New England Journal of Medicine.

Detlef Schuppan, M.D., Ph.D., from the Johannes Gutenberg University in Mainz, Germany, and colleagues conducted a proof-of-concept trial of a six-week treatment with ZED1227 at three dose levels versus placebo among adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point of attenuation of gluten-induced mucosal damage was assessed among 35, 39, 38, and 30 patients assigned to 10-mg, 50-mg, and 100-mg ZED1227 and placebo, respectively.

The researchers found that at all three dose levels, ZED1227 treatment attenuated gluten-induced duodenal mucosal injury. From baseline to week six, the mean ratio of villus height to crypt depth estimated difference from placebo was 0.44, 0.49, and 0.48 in the 10-, 50-, and 100-mg groups, respectively. For the change in intraepithelial lymphocyte density, the estimated differences from placebo were −2.7, −4.2, and −9.6 cells per 100 epithelial cells, respectively, for 10-, 50-, and 100-mg ZED1227. Symptom and quality-of-life scores may have been improved with use of the 100-mg dose.

"Although this trial is very encouraging, whether treatment with ZED1227, and more generally transglutaminase 2 inhibition, in patients with celiac disease will be efficient in real life and during long-term gluten exposure remains to be determined," writes the author of an accompanying editorial.

https://www.medchemexpress.com/zed-1227.html

Oral Transglutaminase 2 Inhibitor Beneficial in Celiac Disease