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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. 

Potato (Solanum tuberosum L.) is a vital staple crop globally, ranking fourth after rice, wheat, and maize in terms of human caloric intake. Its popularity stems from its adaptability across climates, high productivity, nutritional content, and diverse uses in both fresh and processed forms¹. Vegetative propagation through seed tubers remains the principal method of potato cultivation worldwide². Currently, potatoes represent the third most consumed vegetable and the fourth most cultivated food crop globally. In Pakistan, potatoes are grown on approximately 0.19 million hectares, producing about 4.6 million tons annually, with an average national yield of 24.2 tons per hectare. The country holds the 19th position globally in potato production and ranks 12th in exports³.

Potato cultivation in Pakistan follows a multiseasonal calendar: the main crop is planted in autumn (September–January), contributing 80–85% of the total production, with additional harvests in spring (10–15%) and summer (1–2%)⁴. However, potato production is frequently challenged by both abiotic and biotic stressors. Abiotic constraints include temperature extremes, drought, salinity, nutrient imbalances, poor irrigation, and soil degradation, all of which directly affect tuber initiation and development. Biotic pressures such as late blight (Phytophthora infestans), early blight (Alternaria solani), Fusarium wilt, and viral infections (e.g., Potato virus Y and X) further exacerbate yield losses⁵.

An additional constraint arises from postharvest physiological processes, particularly the dormancy phase, which significantly affects the timing and uniformity of sprouting. Dormancy in potato tubers is a genetically and environmentally regulated phase characterized by a temporary suspension of sprout initiation, even under optimal growing conditions. This dormancy begins post-harvest and continues until the apical buds initiate visible sprouting (usually at 2 mm length)⁶. Although dormancy has adaptive significance—allowing tubers to withstand unfavorable storage or overwintering conditions—it presents practical challenges, especially in commercial seed tuber production, where controlled and timely sprouting is essential for uniform crop establishment⁷.

The dormancy period is influenced by several factors, including cultivar genetics, plant maturity at harvest, tuber size and physiological age, and storage conditions (temperature and relative humidity)⁸. Inappropriate dormancy duration can either delay planting or lead to pre-harvest sprouting, both of which reduce seed viability and crop performance. Premature sprouting is associated with increased respiration, carbohydrate depletion, tissue desiccation, and ultimately loss of commercial quality⁹.

To regulate dormancy, both chemical and environmental approaches have been explored. Among chemical treatments, gibberellic acid (GA₃), a naturally occurring plant growth regulator, has emerged as a promising agent for breaking dormancy and promoting sprouting in seed tubers. GA₃ influences physiological and biochemical pathways associated with sprout emergence by enhancing the activity of hydrolytic enzymes, stimulating hormonal signaling, and promoting cell elongation at the tuber eyes¹⁰.

The application of GA₃ initiates key molecular mechanisms, including the upregulation of GA-responsive genes and activation of enzymes such as terpene cyclases and cytochrome P450 monooxygenases, which are involved in endogenous gibberellin biosynthesis and action. These effects collectively contribute to enhanced meristematic activity and earlier sprout initiation. However, GA₃ uptake and efficacy depend significantly on the permeability of the periderm (tuber skin). Since intact skin can impede hormone absorption, higher efficacy is often observed when tubers are freshly harvested, slightly abraded, or have undergone curing¹¹. Environmental factors such as storage temperature and humidity also modulate the tuber’s hormonal responsiveness¹². Moreover, the effectiveness of GA₃ varies across cultivars, and the optimal concentration and immersion time remain inconsistent among studies. For example, while some studies report effective dormancy break at high concentrations (e.g., 1500 ppm GA₃ combined with thiourea), such treatments may not be economically viable or scalable for resource-limited farming systems¹³. Lower concentrations, when properly timed and combined with effective soaking durations, may offer a practical alternative for breaking dormancy without compromising tuber quality or causing hormonal overstimulation.

In Pakistan, the postharvest handling of potato seed tubers remains suboptimal due to limited access to cold storage, poor seed certification systems, and inadequate agronomic support. These issues, coupled with the natural dormancy of locally preferred cultivars such as ‘Ratta,’ often result in delayed or uneven sprouting during planting seasons.

Given this context, optimizing the concentration and exposure duration of GA₃ treatments offers a promising avenue to enhance seed tuber performance. While previous research has established the dormancy-breaking potential of GA₃, there remains a need for cultivar-specific, locally validated recommendations tailored to Pakistan’s agricultural conditions.

The present study was designed to evaluate the effect of different GA₃ concentrations (0, 50, 100, and 150 ppm) and dipping durations (6, 12, 18, and 24 hours) on dormancy break and sprouting behavior of ‘Ratta’ potato tubers. The study aimed to measure key physiological parameters such as sprouting percentage, days to first sprout emergence, number of sprouts per tuber, sprout length and diameter, sprout fresh and dry weights, weight loss during storage, and relative water content of sprouts. These metrics collectively provide a comprehensive understanding of GA₃-induced dormancy release and the quality of subsequent sprouting, offering practical recommendations for seed tuber management.

The outcomes of this research will contribute to developing effective and affordable dormancy-breaking protocols suitable for small- to medium-scale farmers, ultimately supporting improved crop establishment, higher productivity, and enhanced profitability in Pakistan’s potato sector.