New research from Tampere University in Finland shows exciting progress in a new drug for celiac disease. This drug, ZED1227 could be used alongside a gluten-free diet to help manage celiac disease.
In celiac disease, gluten causes inflammation and damage to the intestines. This happens because gluten attaches to specific proteins in the body called human leukocyte antigens (HLA). Before gluten can attach to HLA, an enzyme in the small intestine called transglutaminase 2 (TG2) changes the structure of gluten through a process called deamidation. In people with celiac disease, this deamidation makes gluten more harmful, leading to damage and inflammation in the small intestine. The drug ZED1227 could help by blocking TG2, preventing the harmful changes to gluten and reducing intestinal damage.
In this new study, 58 people with celiac disease were given either 100 mg of ZED1227 or a placebo every day for six weeks while they consumed gluten. Doctors took samples of their intestines before and after the gluten challenge. The results showed that ZED1227 successfully blocked the harmful immune reactions caused by gluten, preventing damage and inflammation in the intestines. The drug was especially effective for people with a specific genetic risk factor. This suggests that using genetic testing to personalize treatment with ZED1227 could be very helpful for celiac patients.
In a previous study led by Professor Emeritus Markku Mäki, the drug ZED1227 was shown to prevent intestinal damage caused by gluten in people with celiac disease by blocking the enzyme transglutaminase 2 (TG2). In this phase 2 trial, researchers examined how ZED1227 works at a molecular level to see if it could be a potential treatment for celiac disease. They also looked at how different genetic factors, especially the HLA-DQ2 gene, influenced the drug’s effectiveness.
“By analyzing the molecular activity of more than 10,000 genes from celiac disease patient biopsies drawn before and after gluten challenge and finding out that orally administered ZED1227, a transglutaminase 2 inhibitor effectively prevented gluten-induced T cell-mediated duodenal mucosal inflammation and morphological damage by inhibiting all known gluten-induced pathogenetic gene changes, I strongly feel we have a successful candidate drug at hand to treat celiac disease”, says professor emeritus, visiting scientist Markku Mäki, MD, PhD, from the Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere university, Tampere, Finland.
Following a strict gluten-free diet is challenging, and studies show that many individuals with celiac disease are inadvertently exposed to gluten. ZED1227 represents a promising adjunct therapy to the gluten-free diet, potentially protecting against intestinal damage even in patients with low levels of gluten exposure. This study underscores the importance of advancing drug trials like ZED1227, as they offer hope for improving medical management and quality of life for individuals with celiac disease, particularly those with specific HLA-DQ genetic profiles. Continued research is necessary to fully understand the effectiveness of ZED1227 and potential application in a clinical setting.
Professor Mäki has a message for the celiac community:
“Research and further development are still out there. The message for patients is that first line therapies will potentially be adjunct to a gluten-free diet, meant to those with symptoms respite their gluten-free diet and or to those where inadvertent gluten ingestion causes small intestinal mucosal lining injury. To reach the final goal, the real unmet need, where a novel therapy replaces gluten-free diet or where patients need not to be so strict on their diet, we need strong future academy-industry-patient partnership undertakings”.
Read more about the study here.
Interested in participating in a celiac disease study? The biggest obstacle in getting a celiac drug to market is recruiting enough patients to participate in clinical trials. Take charge of your celiac disease to make better treatments and, one day, a cure for celiac disease a reality. Learn more at celiac.org/trials.