Transglutaminase 2 inhibitor shows great promise in clinical trial

Transglutaminase 2 (TG2) activity is essential to induce a pathogenic immune response towards gluten in coeliac disease. In a Phase 2 clinical trial, a daily dose of an irreversible TG2-inhibitor prevented gluten-induced mucosal destruction in coeliac patients that consumed gluten daily for 6 weeks. These findings represents a milestone in the search for treatment options for patients with coeliac disease. 

Knut Lundin Foto: Øystein Horgmo,UiO


The trial included more than 160 patients from multiple European countries. About 40 of these participants were Norwegian, where the majority were recruited by J CoDiRC group leader Knut Lundin. Patients were randomized into 4 groups, receiving either placebo or low, medium or high dose of the TG2-inhibitor ZED1227 as a pill 30 minutes prior to consumption of one cookie containing 3g gluten daily for 6 weeks. At the end of the trial, the majority of patients in the placebo group developed mucosal damage and intestinal inflammation. Patients receiving TG2 inhibitor developed less mucosal damage and inflammation. This represents an important proof-of-concept and confirms the central role of TG2 activity in the pathogenesis of coeliac disease. It also proves that TG2 is a druggable target, which has been a long unresolved question.   

Read more about the study here and read the original publication in New England Journal of Medicine and accompanying comment.  



Published Sep. 29, 2021 10:44 AM - Last modified Oct. 13, 2021 1:33 PM