New research at Northwestern Medicine could keep life-threatening anaphylactic shocks caused by allergies under control with a simple pill.
Anaphylaxis, also known as anaphylactic shock, is a severe systemic reaction to allergens that can quite easily prove fatal. At least one in every 50 Americans will experience at least one such event during their lives according to the Asthma and Allergy Foundation of America. They occur within seconds of exposure to the allergen and consist of the airways constricting rapidly -- and dramatically -- which can lead to death.
The most common intervention option used against anaphylaxis is epi-pens. However, they need to be administered to the person while the event is ongoing, placing them at risk of death. A new study is describing a potential treatment in pill form that can be used to prevent such attacks in the first place.
"This pill could quite literally be life-changing and life-saving," said senior and corresponding author Dr. Bruce Bochner, the Samuel M. Feinberg Professor of Medicine at Northwestern University Feinberg School of Medicine.
"Imagine being able to take medication proactively to prevent a serious allergic reaction."
The pill relies on an active ingredient known as a BTK (Bruton's tyrosine kinase) inhibitor. These compounds block allergic reactions by inhibiting the activity of mast cells, which underpin allergic responses. While inhibited, they cannot release histamine and other chemical mediators that produce these reactions.
The team analyzed three different BTK inhibitors, all of which successfully blocked allergic reactions on human mast cells in the lab. The team also developed a "humanized" mouse model -- a mouse whose organs contained transplanted human cells. This animal was used to confirm the efficiency of oral-delivered BTK inhibitors (approved for use by the FDA prior to this study).
Pretreatment with this compound was "remarkably" effective at preventing anaphylaxis and reducing the risk of death during anaphylactic shock after only two doses. These findings strongly suggest that the same effect would be seen in human patients, as the cells transplanted into their organs matured into human mast cells over several months.
The authors explain that such a pill would be the first known preventive measure against anaphylaxis -- our current options only include avoiding the allergen or exposure therapy. Exposure therapy, known as oral food desensitization, involves gradually eating foods to build up a resistance to an allergic reaction.
The current findings could pave the way towards a set of clinical trials testing such oral treatments in humans. Even patients undergoing exposure therapy could benefit from it, by taking the pill as a preventive measure. And, if such a pill proves to be safe and cheap enough for daily use, it could theoretically be used to prevent anaphylactic shocks altogether.
BTK inhibitors are commercially-available, but they're extremely expensive (around US$ 450 per 25mgs).
In the future, the authors plan to investigate whether adding such compounds to epi-pens can help better treat anaphylactic shock.
The paper "Bruton’s tyrosine kinase inhibition effectively protects against human IgE-mediated anaphylaxis" has been published in the Journal of Clinical Investigation.