Thursday, April 20, 2006

A Simple Way to Predict Drug Effects

Experiments with rats suggest that a urine test could accurately predict how an individual will react to medications.

By Duncan Graham-Rowe

An international group of scientists has demonstrated a new tool for personalized medicine that makes it possible to predict nearly any adverse reaction an individual might have to drugs. Rather than being based on genetic screening, which up to now has been the dominant approach to personalized medicine, the new test relies on profiling an individual's metabolic products.

Called pharmaco-metabonomics, the technique involves screening urine for metabolites: small molecules that are involved in or produced by the metabolic processes that sustain an organism.

Besides predicting adverse drug reactions, pharmaco-metabonomics also has the potential to determine more effective dose levels for each individual. "There is no genetic technique that can do that," says Jeremy Nicholson of Imperial College London, the researcher who led the investigation.

The urine test represents a promising new approach that could speed up the slow progress in realizing the potential of personalized medicine. Indeed, efforts to develop tools to tailor drug treatments for individual patients, based on their genes or the proteins they produce, have recently come up against some serious limitations. Since these genomic and proteomic tools rely on genetic factors to predict drug reactions, they fail to take into account environmental factors.

"This is a severe drawback," says Andy Hall, a pharmacogenomics researcher and director of the Northern Institute for Cancer Research at the University of Newcastle-upon-Tyne in England. "The dream of finding single predictor genes for drug response and toxicity is largely unfounded," he says.

Nicholson's proof-of-principle experiment, however, suggests that the new technique is sensitive to not just genetic factors but also the all-important environmental influences. Diet, age, fitness, and the presence of other drugs in the bloodstream can all produce changes in a person's metabolism, changes that can influence how a drug reacts, says Nicholson.

Published in the current issue of the scientific journal Nature, the technique stems from an increasingly popular diagnostic tool called metabolomics. By screening for hundreds of metabolites, it is possible to create profiles of diseases that can then be used for diagnostic purposes.