Using supercomputers to spot drug reactions

Remember the drugs Avandia and Vioxx? Avandia, an anti-diabetic drug released in 1999, worked wonderfully against diabetes. But it was also shown to increase users' risk of heart attacks - a devastating side effect that slashed its sales. And Vioxx, an anti-inflammatory drug, was also linked to an increased risk of heart attacks and stroke, leading manufacturer Merck & Co. to withdraw it from the market.

These are just the drugs that grabbed the headlines. Other side effects from drugs kill more than 100,000 patients a year, according to a study in the Journal of the American Medical Association.

To slash that number, researchers at Lawrence Livermore National Laboratory put their supercomputers to work. They developed a program that determines whether a drug will form a bond with any of hundreds of proteins found in the human body. The research, published recently in the journal PLOS One, found that modeling based on the protein's 3-D structure can pinpoint reactions more quickly than current methods.

From the LLNL release:

"We have discovered a very viable way to find off-target proteins that are important for side effects," said Monte LaBute, PhD,  a LLNL researcher and the paper's lead author. "This approach using high-performance computers and molecular docking to find adverse drug reactions never really existed before."

The team's findings provide drug companies with a cost-effective and reliable method to screen for side effects, according to LaBute. Their goal is to expand their computational pharmaceutical research to include more off-target proteins for testing and eventually screen every protein in the body.

"If we can do that, the drugs of tomorrow will have less side effects that can potentially lead to fatalities," Labute said. "Optimistically, we could be a decade away from our ultimate goal. However, we need help from pharmaceutical companies, health care providers and the FDA to provide us with patient and therapeutic data."

Previously: Mining data from patients' charts to identify harmful drug reactions, Medical journal wins award for reporting on problems with Medtronic bone product and New research scrutinizes off-label drug use
Photo by Lawrence Livermore National Laboratory