The Side Effects of a Misspelling

FOR IMMEDIATE RELEASE:
4/2/2003
Contact:

NIGMS Communications Office
301-496-7301
info@nigms.nih.gov  

Many people are surprised to learn that medicines may only work properly in a subset of the people who take them. If a drug doesn't work properly, a person may experience side effects or no therapeutic effect at all. What's more, whether or not people develop side effects--and if they do, which ones they'll have--varies widely. While many factors such as diet and environment can help account for this variability in drug response, a key determinant is genes. A field of research called pharmacogenetics aims to unravel some of the biological reasons why people react so differently to medicines. NIGMS has made a significant investment in this field and has spearheaded the formation of the Pharmacogenetics Research Network. Pharmacogenetics scientists have found many examples where a change in one or a few of the DNA �letters� that spell out genes can cause people to have different responses to medicines.

In a recent case, Dr. Mark J. Ratain of the University of Chicago, who is a Pharmacogenetics Research Network investigator, identified a group of people who develop a bad reaction to a chemotherapy drug called irinotecan, which is used to treat a variety of solid tumors. He discovered that some people have two extra letters in the gene that instructs the body to make a protein that metabolizes irinotecan and other drugs. Because of this tiny genetic difference, these people have less of the protein that breaks down irinotecan and thus have much higher levels of the medicine in their blood than most people given the same dose. When people with the genetic misspelling took irinotecan, their white blood cell counts dropped dramatically, making them more likely to develop a potentially life-threatening infection. The same people also experienced severe diarrhea, which can cause dangerous fluid loss in people who are already very sick.

Future genetic tests that screen for bad reactions to drugs such as irinotecan may help avoid toxic side effects and help determine the appropriate dose of chemotherapy drugs. Studies are under way to identify additional gene misspellings that could help physicians predict how patients will respond to irinotecan and other medicines.

Writer: Alison Davis, Science Writing Contractor