Humanized mouse model could significantly improve preclinical research on drugs for celiac disease
Celiac disease is an autoimmune disorder in which the immune system reacts to gluten. More than 1% of the population in Germany is affected. In these individuals, gluten proteins found in wheat, rye and barley trigger inflammation in the small intestine, which can damage the intestinal villi and promote disease outside the intestinal tract. Despite following a gluten-free diet, up to 30% of…
Researchers have developed a humanized mouse model that accurately reflects the histologic and immune effects of transglutaminase inhibition in patients with celiac disease. This mouse model, which includes the human antigen-presenting molecule HLA-DQ8, has been shown to develop the typical characteristics of celiac disease, such as changes in the small intestinal mucosa and a pronounced immune response.
The model was validated using a drug candidate called ZED1227, which has been shown to prevent gluten-induced damage to the small intestinal mucosa in clinical trials. The researchers found that the drug candidate had the same protective effects in the mouse model as it did in humans, preserving intestinal villi, reducing inflammation, and mimicking the molecular changes in the immune response.
This optimized mouse model provides a valuable tool for preclinical evaluation of celiac disease therapies and mechanisms, with the potential to accelerate the development of new drugs for the disease.
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