Sherrie Divito, MD, PhD, FAAD, dreams of a day when patients around the world can easily avoid adverse drug reactions while getting the life-saving care they need. In her work as a dermatologist and immunologist over the past decade, she has routinely seen patients experiencing adverse allergic reactions from medications ranging from simple skin rashes to full-blown organ failure and even death. These reactions are unpredictable and can be caused by any drug; from common over-the-counter medications and herbal supplements to prescription medications and cancer treatments.

Sherrie Divito

“Drug reactions are incredibly common yet remarkably understudied,” said Divito. “And they can be very severe. Currently, when someone reacts to a drug we have no way of discerning to what drug they are reacting and patients must stop taking many, if not all, of their medications—that puts both doctors and patients in a very difficult position.”

Divito and her research team have been committed to solving this major public health problem since 2016. They are now on the cusp of developing a new test that will not only screen patients to identify who is at risk of developing a drug reaction, it will also identify which medication is causing the reaction. Their cutting-edge project, called “Safety First! Stopping Adverse Drug Reactions in their Tracks,” is the winner of this year’s BRIght Futures Prize, a competition decided by public voting that awards a one-year $100,000 grant to support Brigham researchers and clinicians as they work to transform and improve patient care.

Divito’s collaborators include Kimberly Blumenthal, MD, MSC of the Department of Allergy and Immunology at Mass General, and Manuel Garber, PhD, of the University of Massachusetts T. H. Chan School of Medicine. The team’s innovative work involves analyzing sequences of T cell receptors, which help the immune system fight disease, and developing a new highly-sensitive testing method, which is currently provisionally patented with full patent pending.

“Our approach overcomes the sensitivity and specificity obstacles that prior tests faced,” Divito said. “Our hope is that it could ultimately be implemented across the world, both as a personalized screening tool and also as a testing tool in patients who have reactions.”

Tackling medicine’s unsolved problems

Roughly 10-20 percent of all hospitalized patients will experience an adverse drug reaction, a major form of which are the allergic reactions that Divito and her team study. Some of the most high-risk drugs include seizure medications, antibiotics, and cancer treatments. But stopping such medications for patients who really need them can cause harm, decrease quality of life, and put them in a life-or-death situation. Because there is currently no way to determine which reactions will progress to life-threatening severity, the standard of care in medicine is to stop any and all potential causative medications in those experiencing reactions.

“We want to save lives. We do not want to cause someone to have a life-threatening reaction,” Divito said. “But we also do not want to stop or avoid a critical medication unnecessarily.” She was initially drawn to pursue practicing medicine by a desire to help people and became a physician scientist so that she could tackle unsolved problems in medicine and alleviate patient suffering. “There is a lot that we still do not understand. The only way we can fix these problems is through research to learn more about the disease process and develop solutions.”

‘A huge leap forward’

Divito and her team began this project by looking at the fundamental pathobiology of disease and observing T cells from the skin and blood. By closely investigating T cell receptors and their response to drugs, they discovered a way to test whether T cells were reacting to certain drugs. They recognized the potential to develop a test that could identify the culprit drug that might be causing a patient’s reaction and then take it a step further by using it to screen people to determine whether they were likely to react to a certain drug.

The team was shocked and delighted to win the BRIght futures prize. The grant will help launch the project’s clinical trial phase and allow them to begin testing as many drugs as possible, starting with the most high-risk drugs, in as many patients as possible. They will also be working hard to license their provisionally-patented method in hopes of quickly making significant strides to help patients who are suffering now.

“Lack of knowledge about these reactions has been a major barrier for progress in clinical care,” Divito said. “The medical field desperately needs to harness science to solve this problem. We are thrilled to receive this support—we believe this project will be a huge leap forward.”

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