A drug already approved by the FDA for asthma has almost eliminated potentially fatal allergic reactions to food allergens in mice-a breakthrough that could lead to new protection for millions of people living with food allergies, reports a new study of northwest medicine.
The results will be published on August 7 in the journal Science.
The discovery intervened after the northwest scientists identified, in mice, a role previously unknown for a gene called DPEP1, which, according to them, is essential in the regulation of anaphylaxis, a rapid and potentially fatal allergic reaction.
Using the zileuton asthma medication to block the path involving this gene, scientists almost eliminated allergic responses in mice which were previously very sensitive to the anaphylaxis induced by food. The mice received peanut extract orally shortly after receiving zileuton while the team was monitoring the symptoms.
“It was in fact shocking to know how Zileuton worked,” said Dr. Stephanie Eisenbarth, author of the co-ennior study, director of the Center for Human Immunobiology and chief of the allergies and immunology division at the Northwestern University Feinberg School of Medicine.
Après traitement avec du zileuton, 95% des souris n’ont montré presque aucun symptôme d’anaphylaxie. Treatment reversed their 95% 95% protected risk. “”
Dr Adam Williams, co-ennior author, associate professor of medicine (allergy and immunology) in Feinberg
The discovery of the new path occurred after a genetic screen before several years, a process where scientists reproduce generations of mice to reduce the specific genes responsible for biological differences, such as sensitivity to food allergy. Une fois que les scientifiques ont constaté que le gène DPEP1 contrôlait les leucotriènes dans les molécules inflammatoires intestinales déjà ciblées par des médicaments contre l’asthme – ils ont testé Zileuton, un médicament approuvé par la FDA qui bloque leur production.
“Approach ready to treat to treat food allergies”
Food allergies are increasing and affects more than 33 million people in the United States-almost one in 10 people. However, predict the risk of an allergic individual of anaphylaxis and prevent the serious reactions of accidental exposure remains difficult.
Currently, there are only two treatments approved by the FDA for certain food allergies – and without healing. One is oral immunotherapy for peanut allergy, which does not work for everyone and can itself trigger anaphylaxis. The other is an expensive injection (omalizumab) which is not effective either for all allergic patients.
Zileuton could offer a new approach: a simple pill that temporarily protects allergic individuals by blocking the anaphylactic path of the body before it activates.
“This is a totally different approach and ready to use to treat food allergies, unlike everything we have tried before,” said Williams. “We have seen tragic, even fatal reactions, hidden ingredients like land peanuts in a sauce. For parents who send their child to a birthday party, or for anyone who steals where they cannot control what is served, it could be a powerful protective drug. »»
Help solve a mystery of food allergy
The results have also shed light on a longtime puzzle in allergic medicine: why some people test positive for food allergens but have no symptoms when they eat food.
“Let’s say you said you are allergic to peanuts based on a blood test, but you have eaten peanuts with your life without any problems,” said Eisenbarth. “This path that we discovered can be an explanation to explain why some of these people are protected. »»
This group was a challenge for clinicians and a source of stress for patients, added Eisenbarth, because current diagnostic tests only consider the risk of allergy, not tolerance.
“Our results open up a whole new field for future research on how people are developing food allergies in the first place, and why some react while others do not do it,” she said.
The breakthrough would not have been possible without long -term investment in scientific research, said Eisenbarth.
“If you asked me five or six years ago to guess the path that would lead to this discovery, I would never have chosen this gene or the leukotrian molecules,” she said.
The other authors of the Northwestern University who supported the study are Danielle Jacobsen, Dr. Eli Olson, Dr. Slim Fourati, Dr Aditi Verma, Caleb McBride, Kara Greenfield and Rebecca Krier-Burris. The work was carried out in collaboration with investigators from the United States, notably Laura Hoyt, Emily Siniscalco, Dr. Elise Liu and Dr. Craig Wilen of the University of Yale.
This study entitled “CYSTEINYL Leucotrians stimulates the intestinal absorption of food allergens to promote anaphylaxis in mice”, was funded by by Ira & Diana Riklis Family Research Award in Food Allergy, The Food Allergy Science Initiative Inc, The Food Allergy Fund, The National Institute of Aleler AI168016, R56 AI155497 U19AI136053) and the National Institute of Health (subsidy P50 CA236733.)
The document will appear in the same issue of Science With another study, led by Dr. Ruslan Medzhitov at the University of Yale, who also discovered the leukotrian path which regulates food allergy in mice by a different approach.