Results from a recent study published in the journal BMC Medicine suggest that a potential treatment for celiac disease, ZED1227, may do more than just protect the small intestine from damage associated with celiac disease; it could potentially prevent downstream changes in the bloodstream as well.
The Problem: TG2
The human body makes something called enzymes, which start important processes in the body to keep it functioning. Many enzymes work in the gut, notifying the body to start digesting things like fats, sugars, and starches.
People with celiac disease produce an enzyme called “transglutaminase 2” (TG2). TG2 attaches to gluten and makes it noticeable to the immune system. The immune system then begins to attack the small intestine in a misguided effort to protect the body from modified gluten.
Some researchers think preventing the TG2 enzyme from attaching to gluten could stop the intestinal attack entirely; if the immune system never notices the gluten, maybe it won’t react at all.
The Study: Testing the Protection
Researchers investigated ZED1227, a drug designed specifically to hinder TG2. By blocking TG2, the gluten is never modified in a way that triggers the immune response in someone with celiac disease. ZED1227 (also known as TAK227) is being jointly developed by Dr Falk Pharma and Takeda.
This study took data from a previous phase 2a clinical trial. 47 trial participants, all of whom had been on a strict gluten-free diet for at least one year and were symptom-free, were asked to undergo a 6-week gluten challenge. Each day they consumed 3 grams of gluten and either 100 milligrams of ZED1227 or a placebo—a placebo looks identical to the medication being tested but contains no active ingredients. Participants also had small intestinal biopsies and gave blood samples before and after the gluten challenge.
To determine how well ZED1227 worked to block the immune response to gluten, researchers used advanced technology to track thousands of signals in the blood, including proteins and lipids that can indicate inflammation and stress. They also compared the intestinal biopsies from before and after the gluten challenge.
The Findings: A Whole-Body Effect
Previous data analysis from this trial showed that ZED1227 reduced intestinal damage from the gluten challenge compared to placebo. This analysis showed that participants taking ZED1227 had changes in only 6 lipids following the gluten exposure, compared to 46 in the placebo group. This indicates ZED1227 reduced the standard immune reaction in celiac disease and stopped changes from happening in the blood.
ZED1227 also appeared to prevent changes in kidney function, which was an unexpected outcome. When looking at test results after the gluten challenge, researchers noticed that those who received the placebo had changes in kidney functioning, but those who received ZED1227 did not—their lab test values remained stable after the gluten challenge.
The changes in kidney functioning were not clinically significant, meaning that participants didn’t notice any symptoms because of it, but it’s still an intriguing difference between the two groups.
Implications of These Findings
This study adds to our understanding of how widespread the effects of being glutened are in people with celiac disease—it affects more than just the small intestine.
More research is needed to fully understand the significance of these changes in lipid and kidney function levels, but the researchers suggested these lipids may be able to serve as future biomarkers. In other words, doctors might one day use changes in kidney function, lipids, or proteins to diagnose celiac disease or measure damage or healing.
What’s Next?
Researchers are studying ZED1227 in additional clinical trials, and Beyond Celiac will continue to track and publicize the progress of ZED1227. To dive deeper into the subject:
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