This Already-Approved Drug Could Stop Food Allergies' Worst Reactions

Gizmodo

6 days ago

Food allergies suck. Beyond placing onerous limits on your diet, their health impacts can totally derail your life, and scientists have been scrambling for years to try and find better, more lasting treatments for these conditions' worst effects. Now, a pair of papers published today in the journal Science unlock crucial new insights into what goes on in the body when anaphylaxis occurs and indicate how an existing medication could one day help prevent these life-threatening allergic reactions.
In one paper, a team of scientists reveal evidence in lab mice for a previously unknown pathway in the gut that may be responsible for some food allergy symptoms. And in the second paper, another team demonstrates that an asthma drug called zileuton blocks a crucial aspect of this pathway in mice, seemingly preventing the expected allergic reactions from happening in most cases. The researchers are now launching a clinical trial to test whether zileuton can pull off the same trick in people.
'If so, this could provide a treatment to prevent anaphylaxis,' Adam James Williams and Stephanie Eisenbarth, both immunologists at Northwestern University who are co-authors on the second paper, told Gizmodo in an email.
Scientists have been working for years to solve a perplexing mystery: Why do some people who have tested positive for food allergies not become sick when exposed to the trigger food, while others with the same allergy develop anaphylaxis?
The researchers describe a gene called DPEP1 that seems to play a surprising role in controlling food-related anaphylaxis in mice: The gene appears to regulate the release of leukotrienes in the gut—these molecules help spark an immune response to an allergen.
When we eat food, most of it is broken down into nutrients for the body to use. But some small amount of it is transported through the gut into the blood as whole proteins, and it's these whole proteins that can trigger a reaction in someone with a food allergy. 'We unexpectedly found that leukotrienes in mice control the amount of whole proteins that are transported across the gut, even in a healthy non-allergic state,' the study authors explained. And scientists already knew that leukotrienes play a part in causing asthma attacks, and several asthma treatments, including zileuton, work by blocking these molecules' activity.
The researchers then gave a dose of zileuton to mice that were allergic to peanuts and then exposed them to their trigger food. They found that the drug blocked the leukotrienes in the mice's gut from working as usual, thereby decreasing the likelihood of an allergic reaction. All told, 95% of the dosed mice failed to show any sign of anaphylaxis, the researchers reported.
The studies are in mice, so how the findings translate to people remains to be seen. The authors also caution that zileuton is not a cure for food allergies. That said, if human trials bear out what was seen in the mice, the drug could be used as a prophylactic that some people could take before a high-risk situation where they're likely to be exposed to such foods. Notably, many people already take zileuton daily for long-term maintenance of their asthma symptoms, suggesting its safety, although it is unclear how its long-term use affects the gut.
If the ongoing clinical trial in humans is successful in showing the drug blocks the same pathway as in mice, the researchers plan to directly test the drug's ability to prevent anaphylaxis in people with food allergies. Beyond the clinical applications, the research poses other questions, the researchers said.
'There are a lot of other exciting questions, like whether this pathway is regulated by things in our environment, such as changes in the microbiome induced by diet,' Williams and Eisenbarth said.