A drug originally designed for chemotherapy successfully mitigated allergic reactions in mice modeling a systemic human allergic response, according to a Northwestern Medicine study published in the Journal of Clinical Investigation.
Pre-treatment with the drug — a Bruton’s tyrosine kinase (BTK) inhibitor — virtually eliminated allergic symptoms in moderate cases and significantly lessened the risk of death in severe allergic reactions.
“I don’t know of any other drug that can protect you from moderate to severe anaphylaxis,” said Bruce Bochner, MD, the Samuel M. Feinberg Professor of Medicine in the Division of Allergy and Immunology and senior author of the study. “That may be a first.”
A previous study authored by Bochner and collaborators had shown that BTK inhibitors can markedly reduce allergic reaction size in skin prick tests, a common procedure where patients are exposed to a small amount of allergen with a small needle. However, it’s impractical to test the drug’s effectiveness at preventing more severe reactions in human patients at this early stage.
Instead, the investigators used a new model in which mice were modified to have human mast cells — the immune cells that cause anaphylaxis — throughout their tissues. The investigators then made the mice allergic to an artificial allergen, and pre-treated one group of these mice with a BTK inhibitor just before administering the allergen to generate a response, while a control group received no pre-treatment.
With a medium dose of allergen, the control group experienced a drop in body temperature and a moderate increase in a clinical score that measures symptoms of anaphylaxis, such as scratching and labored breathing. In contrast, the group that received pre-treatment showed virtually no change in body temperature or in the clinical manifestations of an allergic reaction.
Further, while a large dose of allergen resulted in the death of more than 40 percent of the control group, mice treated with the BTK inhibitor experienced milder drops in body temperature and milder symptoms, but nearly all of those mice survived.
“We gave them a huge slug of allergen, and the drug protected them from dying from anaphylaxis,” Bochner said.
While these results are promising, Bochner noted that the need for pre-treatment limits the situations in which the drug is useful: one must know the allergen exposure is coming.
“For example, if someone is allergic to penicillin, perhaps you could treat them with a drug like this and they could safely take a course of penicillin,” Bochner said.
In addition, BTK inhibitors could also improve food allergy desensitization, a lengthy series of treatments in which food-allergic patients are exposed to increasing amounts of their allergen, hopefully re-training their immune system to recognize the allergen. Pre-treatment with a BTK inhibitor could reduce the chance of a severe reaction and tamp down on moderate reactions so patients can tolerate a higher dose more readily and more quickly.
“This could make food desensitization safer and faster,” Bochner.
Melanie Dispenza, MD, PhD, assistant professor of Medicine at The Johns Hopkins University School of Medicine and a former fellow in the Division of Allergy and Immunology at Feinberg, was the lead author of the study.
Previous studies from the Bochner laboratory were funded by a 2016 Dixon Translational Innovation Award through the Northwestern University Clinical and Translational Sciences Institute (NUCATS), funding that made this current publication possible.
“I want to give kudos to the Dixon Award mechanism. It’s a great example of providing startup funds for science that otherwise might not get the chance,” Bochner said.
Bochner is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The current study was funded by Acerta Pharma, the Ernest S. Bazley Foundation and the Northwestern University Allergy Immunology Research Program T32 AI083216 from the National Institute of Allergy and Infectious Disease.