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.
AUGUSTA, Ga. -- It can be a game of Russian roulette. When doctors try out different meds on patients, they don't always know how they'll respond -- and the wrong guess can have deadly consequences. Now, there's a new way to tell how people break down certain drugs, paving the way for personalized medicine.
Playing tug of war with her horse, Shilo, is the same kind of struggle 62-year-old Lynne Tollison has always had with doctors. She says, "This is the classic answer: 'She obviously takes a lot of medication, and her body builds up tolerances,' like I'm a drug addict."
Pain medications haven't worked for Tollison's arthritis, and side effects prevented her from taking a drug for bipolar disorder. "You get to the point where you don't go to a doctor or dentist when you need to go, because what they give you is not going to help, so you don't go!"
But now, a first-of-its kind gene chip test is solving years of medical mystery. It tells doctors how a person processes about 25 percent of drugs on the market, including most antipsychotic meds.
Psychiatrist Adriana Foster, of the Medical College of Georgia in Augusta, says, "Our slogan is start low and go slow, but patients can't always afford that because they could be terribly depressed and at risk of suicide."
Here's how the test works. First, blood is drawn and DNA is extracted. Then scientists isolate the two genes that break down drugs and look for mutations.
Doctors hope the test will pave the way for a new generation of medicine.
"We have been, you know, waiting for these kind of things for a long time, and now it's here," Zixuan Wang, a microbiologist at Medical College of Georgia, tells DBIS.
For Tollison, who just found out she is a poor metabolizer, it means validation and hopefully finding effective treatments that will allow her to take care of her family. "I have to struggle to keep myself together sometimes, so that would be wonderful," she says. If a person is a poor metabolizer, they may be susceptible to side effects and will stop taking a much-needed drug because of them. If a person is a fast metabolizer, the drug may not work, and a depressed patient could commit suicide in that time. Right now the gene chip test costs between $600 and $1,000, but in the future it could be something insurance would cover. And the researchers say it could ultimately be cost-effective as there would be fewer trial-and-error prescriptions made.
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.
Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.