Transglutaminase 2 inhibitor for treating Celiac disease – A randomized study
A wonderful study that was published in a leading medical journal in July 2021 (PMID 34192430) examined the effectiveness of a molecule / experimental drug for Celiac disease.
The prevalence of Celiac around the world is 2% and in my opinion it is one of the most important medical conditions in pediatric medicine that can be diagnosed by a simple blood test. Therefore, I recommend to read about Celiac disease in this website (upcoming link) and consider a screening test to your children.
The only treatment for Celiac is a gluten-free diet, but it is known that even in children (or adults) who obtain a gluten free diet and in cases where the antibodies level in the blood goes down to normal, the healing of gastrointestinal mucosa is known to take a long time.
Transglutaminase 2 is a self-antigen which is located in the intestines and causes Celiac. Therefore, if there is a medicine (or an experimental molecule) that can inhibit this antigen, it is possible that the use of it will prevent the disease. Phase 1 safety studies have already been conducted on this molecule called ZED1227 and the purpose of the present study is to report the results of phase 2 which includes a larger amount of participants.
Methods – Patients aged 18-65 with a proven biopsy diagnosis and a positive genetic test for an HLA that was previously found to be Celiac related, were recruited for the study. They were recruited from 20 worldwide sites in seven countries. The patients had been on a gluten-free diet and had had a negative antibodies test for at least a year before being enrolled to the study.
What was the intervention?
Prior to the study all participants underwent a gastroscopy biopsy. Later, some of the participants received the medicine in the morning (in 3 different doses) and others received placebo, for the period of six weeks. After having received the medicine in the morning, all participants (including those who got the placebo) were exposed to gluten by eating a cookie containing gluten (3 grams’ gluten).
The study was random and double-blind. That is, neither the physicians nor patients knew if they take the medicine or the placebo.
During the six weeks of consuming the gluten, the participants kept a diary and reported various symptoms, including potential side effects and at the end of six weeks of intervention the patients underwent another biopsy that was compared to the first.
Results – 163 participants took part in the study. Without going too deep into the details of the study, the study group who received the experimental drug, in different doses and particularly in the higher dose, showed lower vulnerability of the intestinal mucosa to gluten exposure.
And what about side effects?
It was hard to distinguish between the drug side effects and the effects of Celiac patients starting to consume gluten but also here, there were no differences between the groups (which indicated safety).
Discussion – I don’t know if this will be the drug that will “cure” Celiac in the future and will perhaps enable those who are gluten sensitive to eat gluten without trouble. I do know that science is progressing and that a study such as this brings significant positive news to children (and adults) with Celiac and to their families. I am also aware of the study’s limits and that the solution is not as simple.
I do not know if it will take 5 years or maybe 15, but science and medicine are progressing and I am convinced that Celiac too, will have this solution or another.
One can dream, right?