An existing asthma drug has been shown to almost completely prevent life-threatening allergic reactions to food in mice, after researchers found a previously unknown genetic pathway linked to anaphylaxis.
A drug already approved by the U.S. Food and Drug Administration (FDA) for asthma has been found to nearly eliminate life-threatening allergic reactions to food in mice – a breakthrough that could lead to new protection for millions of people with food allergies, according to a new Northwestern Medicine study published in Science.
A new role for the DPEP1 gene
In mice, discovery identified a previously unknown role for a gene called DPEP1, which they found is essential in regulating anaphylaxis – a rapid and potentially fatal allergic reaction.
By using the asthma drug Zileuton to block the pathway involving this gene, the researchers nearly eliminated allergic responses in mice that were previously highly susceptible to food-induced anaphylaxis. The mice were given peanut extract orally shortly after receiving Zileuton while the team monitored for symptoms.
“It was actually shocking how well Zileuton worked,” said co-senior study 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 percent of the mice showed almost no symptoms of anaphylaxis. The treatment reversed their risk from 95 percent susceptible to 95 percent protected,” added co-senior author Dr Adam Williams, an associate professor of medicine (allergy and immunology) at Feinberg.
From genetic screening to drug testing
The breakthrough came after a yearslong forward genetic screen – a process where scientists breed generations of mice to locate specific genes responsible for biological differences, such as susceptibility to food allergy.
Once the scientists found that the DPEP1 gene-controlled leukotrienes in the gut – inflammatory molecules already targeted by asthma drugs – they tested Zileuton, which blocks their production.
‘Out-of-the-box’ food allergy protection
Food allergies affect more than 33 million people in the US, and it’s rising. Still, predicting an allergic person’s risk of anaphylaxis and preventing severe reactions from accidental exposure remains challenging.
Currently, there are only two FDA-approved treatments for certain food allergies – and no cure. One is an oral immunotherapy for peanut allergy, which can itself trigger anaphylaxis, and the other is a costly injection, called omalizumab, that isn’t effective for all patients.
Food allergies affect more than 33 million people in the US, and it’s rising.
Zileuton could offer a simple pill that temporarily shields allergic individuals by blocking the body’s anaphylactic pathway before it activates.
“This is a totally different, out-of-the-box approach to treat food allergy, unlike anything we’ve tried before,” Williams said. “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.”
The Northwestern team launched a small early-stage clinical trial in July to test whether blocking this newly identified pathway with Zileuton in humans is as effective as it was in mice.
Explaining a long-standing allergy puzzle
The findings may also explain why some individuals test positive for food allergens but experience no symptoms when they eat 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,” Eisenbarth said. “This pathway we discovered may be one explanation for why some of those people are protected. Our findings open a whole new area for future research into how people develop food allergies in the first place, and why some react while others don’t.”