Allergic Drug Reactions: How One Protein Changes Everything
Allergic drug reactions affect patients around the world every single day, causing itchiness, swelling, and rashes as an unwanted part of treatment. These reactions, known as pseudo allergies, can be so severe that they prevent patients from taking needed medications — and in some cases can even prove fatal. Until now, it had never been conclusively shown what triggers these allergic drug reactions. A new study published in the journal Nature has changed that.
“We are in the very early stages but we now understand how these pseudo allergies are happening,” said Marianna Kulka, an adjunct assistant professor in the University of Alberta’s Department of Medical Microbiology and Immunology and project group leader with the National Institute for Nanotechnology. “This is a very large step forward in many ways.”
The Single Protein Behind Allergic Drug Reactions
Researchers from the University of Alberta’s Faculty of Medicine and Dentistry and Johns Hopkins University identified a single protein as the root cause of allergic drug reactions to medications and injections. They are now exploring ways to block the protein and reduce the painful side effects caused by these reactions.
“The drugs currently being used treat some very nasty diseases and they are very effective at that. But side effects are a huge problem. If we can avoid these side effects by finding a way to block this problematic protein, we can really design drugs that are effective and safe,” said Kulka, a co author on the study.
How the Research Was Conducted
The researchers focused on allergic drug reactions triggered by medicines prescribed for a number of conditions ranging from prostate cancer to diabetes to HIV. These reactions are different from the allergic reactions caused by food or experienced by hay fever sufferers — they represent a distinct biological mechanism that had remained poorly understood until this breakthrough.
The scientists tested laboratory models with and without a single protein — named MRGPRB2 — on their cells. The laboratory models without the protein did not suffer negative effects despite being given drugs known to provoke allergic drug reactions in other models.
Benjamin McNeil, a post doctoral fellow at Johns Hopkins University and study co author, noted: “It’s fortunate that all of the drugs turn out to trigger a single receptor — it makes that receptor an attractive drug target.”
What This Means for Drug Development
If a new drug could be developed to block the MRGPRB2 protein receptor, it would significantly lessen the side effects patients currently endure from allergic drug reactions. Kulka believes that with time, many painful reactions from medications can be avoided entirely.
“By understanding how they are happening we can really help to avoid some of the pitfalls of designing drugs that cause the pseudo allergies. We’ve got big plans in the future for trying to expand this research and better understand how this works.”
This discovery has major implications for clinical trial design as well. Allergic drug reactions are one of the most common reasons participants drop out of trials or require dose modifications, making any breakthrough in understanding or preventing them directly relevant to research outcomes.
Understanding how discoveries like this move from basic science into clinical application requires understanding the trial process itself. Our introduction to clinical trials explains how findings like this one progress from laboratory models through Phase I to Phase IV human studies.
For those interested in how personalized approaches to drug design are evolving, our article on personalized medicine drug discovery explores how data and genomics are reshaping how safer and more targeted therapies are developed.
According to the U.S. Food and Drug Administration, adverse drug reactions represent one of the leading causes of hospitalization and healthcare costs in the United States — making research into allergic drug reactions a critical public health priority.
Source: University of Alberta | February 4, 2015