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Gene Chip for Personalized Meds

Psychiatrists Can Now Predict An Individual Patient's Response To A Drug

August 1, 2006

The first in a new generation of gene microarrays, computer chips that chemically or electrically express DNA, can predict how a person's body will metabolize about 25 percent of drugs on the market, including most antipsychotic medications. The chip tests for mutations in genes that break down drugs. Molecular biologists say that slow metabolizers may be susceptible to side effects, while fast metabolizers may not find a drug effective.

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Science Insider

Science behind the news is funded by a generous grant from the NSF

BACKGROUND: Researchers are using a new test that looks at how each person's body digests, absorbs and circulates drugs. This will allow doctors to prescribe carefully tailored dosages, without weeks of trial and error. This in turn will help patients get the best treatment and lower side effects. It's one of the first steps toward personalized medicine. The test will initially be used to determine the best dosages of commonly used psychiatric drugs. A second test is being developed to look at how the body processes the most common drugs used in chemotherapy.

IMPROVED DRUG EFFICACY: The bloodstream is the primary means for transporting drugs through the body, and the liver is the central places the body processes -- or "metabolizes" -- drugs. A drug's effect depends less on chemistry than on the way it navigates through the body: being broken down by the liver, absorbed by the intestines and stored in fat cells. And that process can be affected by how each person's body uses drugs differently.

THE ROLE OF METABOLISM: The body's processing, or metabolic, rate changes from person to person, depending on a wide variety of factors: age, sex, and amount of lean body mass, for example. If someone has a low metabolism, the drug will not be broken down properly, staying in the liver at high concentrations and causing side effects. Side effects from medications are the fourth leading cause of death in the United States. This kind of patient needs lower doses of the drug. On the other hand, someone with a very fast metabolism will break the drug down so quickly that it will not be effective. Those people require higher doses. Even high amounts of otherwise beneficial vitamins and minerals can lead to toxic side effects.

HOW IT WORKS: Tiny labs-on-a-chip (called microarrays) have been on the market for several years. The AmpliChip CYP450 test analyzes two genes involved in metabolizing about 25 percent of all drugs, including many psychiatric drugs. A blood sample is inserted into the chip, which rapidly searches the sample for telltale genetic variations. Microarrays are an example of microelectro-mechanical systems. MEMs integrate electronic and moving parts onto a microscopic silicon chip, making them ideal for new sensor technology. A MEMS device is usually only a few micrometers wide; for comparison, a human hair is 50 micrometers wide.

ABOUT MICROFLUIDICS: Microfluidics studies how fluids behave at microscopic levels: volumes of water, for example, that are thousands of times smaller than a single droplet. At these size scales, tiny effects that wouldn't be noticeable on a large scale play a much larger role. By understanding these effects, scientists can use them manipulate fluids on the microscopic scale. This has led to such beneficial technologies as ink jet printers and labs-on-a-chip for fast and cheap DNA sequencing.

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Did you know?...

An estimated 5 percent of the population has ultra-fast metabolisms, while another 5 percent of the population has very slow metabolisms. Most of us fall into the middle range, where recommended dosages of drugs generally work very well.

More information on this story

Adriana Foster
Deptartment of Psychiatry and Health Behavior
Medical College of Georgia
Augusta, GA
Tel: 706-721-7488
afoster@mcg.edu

Zixuan (Zoe) Wang
Molecular biologist
Georgia Esoteric & Molecular Diagnostic Labs, LLC
Medical College of Georgia
Augusta, GA
Tel: 706-721-3122
zwang@mcg.edu


© 2008 American Institute of Physics