A recent research study looked into the potential of using a transglutaminase 2 inhibitor as a treatment for celiac disease. Previous research on tissues has indicated that the ZED1227 transglutaminase 2 inhibitor can prevent damage to the intestines caused by gluten. The latest study, which analyzed the molecular activity of over 10,000 genes, presents compelling evidence that a successful drug for treating celiac disease may be on the horizon.
When people consume gluten-containing cereals like wheat, barley, and rye, it triggers an abnormal immune response in the small intestine, leading to the development of celiac disease in about 2% of the population. Currently, there is no medication available for treatment, and individuals have to adhere to a strict gluten-free diet for life. However, even with strict adherence to the diet, symptoms and intestinal damage can still occur due to hidden gluten.
Keijo Viiri, who is an Adjunct Professor of Cellular and Molecular Biology, explains, “Blood tests and traditional tissue examinations may not always provide a complete picture of the condition of the intestinal mucosa. Our previous research has shown that despite the appearance of healthy intestinal tissue, molecular changes can still be present, affecting the expression of genes involved in the absorption of vitamins and minerals. This could explain the common deficiencies in trace elements observed in celiac patients despite following a gluten-free diet.”
In a prior tissue study led by Professor Emeritus Markku Mäki from Tampere University, the ZED1227 transglutaminase 2 inhibitor was found to prevent gluten-induced intestinal damage in celiac disease patients. However, the exact mechanisms of action are not fully understood. A new international study, spearheaded by Tampere University, delved into the molecular processes to explore ZED1227 as a potential candidate for celiac disease treatment.
The study assessed the effectiveness and molecular actions of ZED1227 by examining intestinal biopsies of celiac patients. Biopsies were taken after an extended period of a gluten-free diet, and then again after six weeks of gluten exposure, during which patients were given 3 grams of gluten per day. Some patients were also administered a daily dose of 100 milligrams of ZED1227, while others received a placebo.
Viiri notes, “Through gene activity analysis, we found that oral intake of ZED1227 effectively prevented gluten-induced intestinal damage and inflammation. In the group receiving the drug, the activity of genes responsible for nutrient and mineral absorption returned to levels seen before gluten exposure.”
Within the intestines of individuals with celiac disease, inflammation and mucosal damage occur through a series of cellular and molecular processes when gluten attaches to human leukocyte antigen (HLA) molecules. However, gluten can only bind to HLA after the transglutaminase 2 enzyme in the small intestine chemically alters, or deamidates, the gluten structure. The effectiveness of ZED1227 lies in its ability to hinder this deamidation process.
Viiri emphasizes, “It is too early to claim that ZED1227 will be the definitive celiac disease treatment, replacing the need for a gluten-free diet. Yet, it stands as a strong candidate for a medication that could complement a gluten-free diet. If and when ZED1227 becomes available as a medication, it could also be beneficial to employ personalized medicine, particularly for celiac patients with the high-risk HLA genotype.”
