Creative Minds: Taking Aim at Adverse Drug Reactions

Posted on November 30, 2017 by Dr. Francis Collins

Sherrie Divito

As a practicing dermatologist, Sherrie Divito sees lots of patients each week at Brigham and Women’s Hospital, Boston. She also sees lots of research opportunities. One that grabbed her attention is graft-versus-host disease (GvHD), which can arise after a bone-marrow transplant for leukemia, lymphoma, or various other diseases. What happens is immune cells in the donated marrow recognize a transplant patient’s body as “foreign” and launch an attack. Skin is often attacked first, producing a severe rash that is a harbinger of complications to come in other parts of the body.

But Divito saw something else: it’s virtually impossible to distinguish between an acute GvHD-caused rash and a severe skin reaction to drugs, from amoxicillin to carbamazepine. In her GvHD studies, Divito had been researching a recently identified class of immune cell called tissue-resident memory T (Trm) cells. They remain in skin rather than circulating in the bloodstream. The clinical similarities made Divito wonder whether Trm cells may also help to drive severe skin allergies to drugs.

Divito has received a 2016 NIH Director’s Early Independence Award to find out. If correct, Divito will help not only to improve the lives of thousands of people with GvHD, but potentially benefit the millions of other folks who experience adverse reactions to drug.

Lack of suitable tissue samples has hampered research on adverse drug reactions. But that won’t be a problem for Devito. She will begin by tapping into a vast collection of skin biopsies from people who’ve suffered adverse drug reactions. The collection has been essentially untouched for years in the pathology warehouses of nearby Harvard University. The reason: the samples are embedded in paraffin wax, making DNA extraction and analysis a challenge. Divito plans to use new imaging and genetic analysis technologies to examine the skin samples for various types of immune cells, including those potentially troublesome Trm cells.

She is also launching a prospective, or forward-looking, study of people who are being treated for a suspected drug reaction. In addition to the standard biopsy of affected skin, Divito will collect samples of the patient’s healthy skin and blood to search for further biological clues. She also plans to develop much-needed mouse models of drug allergies.

Drug allergies affect about 7 percent of people; in some cases, those reactions can be dangerous or even deadly. Even when drug reactions aren’t debilitating, they can still be a big problem, forcing doctors to prescribe alternative drugs as a precaution. These alternative drugs may be less effective or carry a greater risk of other serious side effects. Also, when people take multiple prescription drugs, it can be tricky to tell which particular drug is responsible for an allergic reaction.

Divito envisions development of a test that could be used to test small samples of a person’s skin for potential reactions to certain drugs. Her aim is to determine in advance which drugs an individual should avoid due to risk of allergic reactions.

While she’s anxious to learn if Trm cells play a role in drug reactions, Divito is equally invested in developing technologies and approaches to allow researchers elsewhere to explore their own hypotheses. As she and others take advantage of these tools and learn more about the underlying biology, the hope is to advance new and more effective ways to treat both drug reactions and GvHD—a big win for everybody.

Links:

Drug Allergies (National Library of Medicine/NIH)

Graft-versus-Host Disease (National Library of Medicine/NIH)

Sherrie Divito (Brigham and Women’s Hospital, Boston)

Divito NIH Project Information (NIH RePORTER)

NIH Director’s Early Independence Award (Common Fund)

NIH Support: Common Fund