New study shows promising celiac disease drug's molecular efficacy

A recent investigation led by researchers at Tampere University explored the potential of a transglutaminase 2 inhibitor as a drug treatment for celiac disease. This condition is triggered by consuming gluten-containing cereals such as wheat, barley, and rye, resulting in an abnormal immune response in the small intestine. Affecting up to 2% of the population, celiac disease currently has no pharmaceutical treatment, with patients relying solely on a strict gluten-free diet. However, even those adhering to this diet can experience symptoms and intestinal damage due to inadvertent gluten exposure.

Previous research has demonstrated that the ZED1227 transglutaminase 2 inhibitor can prevent gluten-induced damage to the intestines. The new study provided strong evidence that this inhibitor might be the first successful drug to treat celiac disease. The analysis, which examined the molecular activity of over 10,000 genes, suggests that ZED1227 plays a significant role in mitigating gluten-induced intestinal harm.

Keijo Viiri, Adjunct Professor of Cellular and Molecular Biology, noted that while traditional blood antibody and tissue tests might not fully reveal the condition of the intestinal mucosa, earlier studies indicate that the tissue can appear healthy yet still bear molecular scars. These scars could lead to deficiencies in the absorption of vitamins and trace elements, explaining why celiac patients often face nutritional shortfalls despite adhering to a gluten-free diet.

A previous tissue study coordinated by Professor Emeritus Markku Mäki from Tampere University showed that ZED1227 is capable of preventing gluten-induced damage in celiac patients. However, the exact mechanisms by which it operates remain unclear. This new international study aimed to delve deeper into the molecular mechanisms and assess the efficacy of ZED1227 as a potential drug for celiac disease.

The study involved analyzing intestinal biopsies from celiac patients who had followed a long-term gluten-free diet. These biopsies were then taken again after a six-week period during which the patients consumed 3 grams of gluten daily. During this period, some patients received a daily dose of 100 milligrams of ZED1227, while others were given a placebo.

Viiri stated that the study revealed orally ingested ZED1227 successfully prevented gluten-induced damage and inflammation in the intestinal mucosa. Additionally, in patients who received the drug, the gene activity responsible for nutrient and trace element absorption returned to pre-gluten exposure levels.

In celiac patients, gluten binds to human leukocyte antigen (HLA) molecules, triggering inflammation and mucosal damage through various cellular and molecular events. However, for gluten to bind to HLA, the transglutaminase 2 enzyme in the small intestine must first chemically modify the gluten, a process known as deamidation. The effectiveness of ZED1227 lies in its ability to prevent this deamidation.

Viiri emphasized that it is too early to definitively state that ZED1227 will become the future medication for celiac disease, potentially eliminating the need for a gluten-free diet. Nevertheless, it remains a promising drug candidate that could be used alongside a gluten-free diet. Viiri also highlighted the potential for personalized medicine, particularly for celiac patients with a high-risk HLA genotype, if or when ZED1227 becomes available.