Celiac disease is an inflammatory disorder in which T cells cause mucosal damage in the small intestine. These T calls are activated by small intestinal transglutaminase 2 that causes deamidation of glutamine residues in gluten peptides, inhibition of transglutaminase 2 could therefore become a potential treatment for celiac disease. Current treatment of celiac disease consists of a lifetime of gluten free diet, which is extensive and challenging to continu. A medical treatment could thus revolutionize treatment and improve quality of life of these patients substantially.
In this phase II trial the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, was investigated at three dose levels compared with placebo. Patients included in the study were adults with well-controlled celiac disease who underwent a daily gluten challenge.
Only 30/40 patients in the placebo group had adequate duodenal-biopsy samples after the treatment period, versus 35/41 patients assigned to the 10-mg ZED1227 group, the 39/41 assigned to the 50-mg group, the 38/41 assigned to the 100-mg group. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 44 – 48% depending on dosage. Use of the highest dose may have improved symptom and quality-of-life scores. The most common adverse events were equal in all groups including placebo.
The authors conclude that treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease exposed to a diet containing gluten. This could be an exciting prospect for patients with celiac disease!
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