What if a common asthma drug could stop severe food allergy reactions before they start?
A new study from Northwestern University, published in Science, found that the drug zileuton dramatically reduced anaphylaxis in allergic mice by blocking allergen absorption in the gut. Researchers have now launched a clinical trial to see if the same holds true in humans.
Current food allergy drugs don’t prevent anaphylaxis
Food allergies affect over 33 million people in the US and are becoming more common. For some, even a trace of an allergen can cause anaphylaxis – a rapid, dangerous reaction that’s hard to predict and difficult to prevent.
There are currently only two drugs that are approved by the US Food and Drug Administration (FDA) for allergies: a peanut immunotherapy and omalizumab – an antibody injection – and both come with issues. The immunotherapy isn’t effective for everyone and can cause reactions itself. Omalizumab is also expensive and not widely used.
There is still no way to reliably block anaphylaxis if someone accidentally eats the wrong thing.
One puzzle in allergy medicine is why some people with allergy antibodies (IgE) don’t react when they eat the food. It’s known as “sensitized tolerance,” and the biology behind it isn’t clear.
Using mouse models, the latest study explored how the gut absorbs allergens and what makes some animals more susceptible to reactions than others. The team set out to find the biological switch behind that difference – and whether it could be blocked with a drug.
An existing asthma drug protected allergic mice
The researchers started with two types of mice: one strain (C57BL/6) that doesn’t react to oral allergens, and another (C3H/HeJ) that does.
Despite having similar levels of allergy antibodies, only the susceptible mice developed anaphylaxis after eating allergens. The key difference was how their guts handled allergen absorption.
Using a genetic screen, the team identified a gene called Dpep1 as a driver of this difference. This gene makes an enzyme that breaks down cysteinyl leukotrienes, molecules that are better known for their role in asthma.
In the susceptible mice, Dpep1 activity was lower, which meant higher levels of leukotrienes in the gut, leading to more intact allergens passing through the gut wall and triggering immune cells.
In parallel, the team found that genes involved in leukotriene production were more active in allergic patients who reacted to smaller amounts of peanut during food challenges.
Blocking Dpep1 in resistant mice with a drug called cilastatin made them vulnerable to anaphylaxis. Boosting Dpep1 activity or keeping the resistant gene variant protected the mice.
The team then tested zileuton, a drug already approved for asthma, which blocks leukotriene production.
“It was actually shocking how well zileuton worked,” said corresponding author Dr. Stephanie Eisenbarth, the director of the Center for Human Immunobiology and chief of the Division of Allergy and Immunology at Northwestern University Feinberg School of Medicine.
“After treatment with zileuton, 95% of the mice showed almost no symptoms of anaphylaxis. The treatment reversed their risk from 95% susceptible to 95% protected,” added co-senior author Dr. Adam Williams, an associate professor of medicine at Northwestern University Feinberg School of Medicine.
Could this drug prevent food allergy reactions in people?
This study flips the usual approach to food allergy treatment. Instead of targeting the immune system, it focuses on the gut, specifically, how allergens cross the gut lining. Blocking that passage, rather than blocking the allergic reaction itself, is what made the difference.
“This is a totally different, out-of-the-box approach to treat food allergy, unlike anything we’ve tried before,” said Williams. “For parents sending their child to a birthday party, or for anyone flying where they can’t control what’s being served, this could be a powerful protective drug.”
The findings also help explain why some people test positive for food allergies but don’t react when eating the food.
“Let’s say you’re told you’re allergic to peanuts based on a blood test, but you’ve eaten peanuts your whole life without any problems. This pathway we discovered may be one explanation for why some of those people are protected,” said Eisenbarth.
Still, the work so far has only been in mice. Human gut biology may respond differently, and zileuton’s effects in this setting haven’t been proven yet. A small clinical trial is underway, and the team hopes it will confirm what was observed in mice.
Since zileuton is already FDA-approved for asthma, researchers see potential for faster translation if the human trials are successful.
“If you’d asked me five or six years ago to guess the pathway that would lead to this discovery, I never would have picked this gene or the leukotriene molecules,” said Eisenbarth.
“Our findings open a whole new area for future research into how people develop food allergies in the first place,” she added.
Reference: Hoyt LR, Liu E, Olson EC, et al. Cysteinyl leukotrienes stimulate gut absorption of food allergens to promote anaphylaxis in mice. Science. 2025. doi: 10.1126/science.adp0240
This article is a rework of a press release issued by Northwestern University. Material has been edited for length and content.