A drug approved for asthma treatment has shown significant effectiveness in preventing severe allergic reactions to food in mice, according to a new study from Northwestern Medicine. The research, published August 7 in Science, found that the drug Zileuton blocked anaphylaxis—a rapid and potentially fatal allergic reaction—by targeting a newly identified genetic pathway.
The study focused on the gene DPEP1, which researchers discovered plays a crucial role in regulating anaphylaxis. By administering Zileuton to mice highly susceptible to food-induced anaphylaxis, scientists observed that 95% of treated mice were protected from symptoms after exposure to peanut extract.
“It was actually shocking how well Zileuton worked,” said Dr. Stephanie Eisenbarth, 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 Dr. Adam Williams, associate professor of medicine (allergy and immunology) at Feinberg.
The discovery followed years of genetic screening in mice to pinpoint genes linked to food allergy susceptibility. Once researchers determined that DPEP1 controlled leukotrienes—molecules involved in inflammation already targeted by asthma medications—they tested Zileuton’s effect on this pathway.
Food allergies affect more than 33 million people in the United States, making up nearly one in ten Americans. Current FDA-approved treatments are limited: oral immunotherapy for peanut allergy and omalizumab injections do not work for all patients and can be costly or trigger reactions themselves.
Zileuton may offer a different solution as a pill taken before potential allergen exposure, temporarily blocking the body’s anaphylactic response. “This is a totally different, out-of-the-box approach to treat food allergy, unlike anything we’ve tried before,” said first author Laura Hoyt. “We’ve seen tragic, even fatal reactions from hidden ingredients like ground peanuts in a sauce. 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.”
A small clinical trial began in July to test whether blocking this pathway with Zileuton is as effective in humans as it was in mice.
The findings also help explain why some individuals who test positive for food allergens experience no symptoms when eating those foods. “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,” Eisenbarth said. “This pathway we discovered may be one explanation for why some of those people are protected.”
Eisenbarth noted that these results open new directions for future research into how food allergies develop and why only some people react despite similar diagnostic results.
“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,” she said.
The study included contributions from several other Northwestern University researchers as well as collaborators from Yale University. Funding came from multiple sources including the Ira & Diana Riklis Family Research Award in Food Allergy and grants from national health organizations.
Another paper appearing in the same issue of Science by Yale University researchers also identified the leukotriene pathway’s role in regulating food allergy through a separate approach.