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Genetic Chips
Drugs Could Be Tailored For Genes

Many of us who take medications for psychiatric illnesses have experienced medication changes, sometimes on a rather frequent basis.  The explanation that not every drug is effective for every person is and has been accepted.

But what if a susceptibility to a particular drug could be discerned ahead of time...or a dastardly reaction?

I found this article (I apologize that I do not know the url source) very interesting and promising in terms of the illness we share.

04:59 PM ET 06/05/00

Drugs Could Be Tailored for Genes
By LAURAN NEERGAARD=
AP Medical Writer=

WASHINGTON (AP) _ Doctors accused her of being a hypochondriac:

The woman suffered dizziness and a racing heartbeat from each antidepressant she tried, even though she was taking doses normally far too low to cause side effects.

The desperate woman finally saw Dr. Raymond Woosley, who scanned her DNA with a special “gene chip” and discovered she actually has a genetic quirk that makes her super-sensitive to certain medicines.

She’s lucky: Some people die while taking some of the world’s most popular drugs _ from antibiotics to heartburn remedies _ all because no one knew their genes made them uniquely susceptible to devastating side effects.

That’s about to change. A new science called “pharmacogenomics” aims to curb the problem by replacing today’s one-dose-fits-all culture with simple tests to help doctors customize prescriptions, picking the safest, most effective drug for each patient’s DNA.

Already, Woosley and colleagues are testing the new technology at Georgetown University Medical Center. Just swab the inside of a patient’s cheek for a DNA sample, and run it over a tiny glass gene chip the size of a postage stamp. The chip detects an errant enzyme system called p450 that affects how safely people metabolize dozens of popular medicines.

P450 testing is so successful that Woosley just launched an international registry, closely watched by the Food and Drug Administration, to investigate other gene variations that make some people collapse with a lethal irregular heartbeat after taking any of 50 common drugs.

And some companies are poised to begin offering, possibly within the next year, the first direct-to-consumer pharmacogenomic testing. The idea: Instead of waiting for gene chips to reach your doctor’s office, just send a cheek swab to a gene-testing laboratory to see if you’re at risk from certain drugs, explains Josh Baker, president of PPGx Inc., one company hoping to offer consumer testing. Then give the test results to your doctor.

“It’s very clear this concept works,” says Woosley, a clinical pharmacologist and heart specialist. New research to pinpoint who’s at risk “is some of the most exciting stuff I’ve ever seen.”
Even the best medicines don’t help everyone. Drugs are sold after they prove an effect on the average disease sufferer, not every individual. So there’s little way to know who’s wasting time on treatment that will fail, and who will suffer side effects. Some 2 million Americans are hospitalized annually for side effects, and 100,000 die.

Pharmacogenomics aims to improve that.

This is not your standard gene test. It doesn’t reveal disease-causing gene mutations. Instead, tests hunt subtle genetic variations called polymorphisms that can determine reactions to medications.
Take p450, the best-known family of drug-processing enzymes. An estimated 7 percent of Americans lack certain p450 enzymes, allowing some drugs to climb to toxic levels in their bodies. Other people’s p450 enzymes work too fast, clearing a drug out of the bloodstream too fast for it to fight disease.

P450 isn’t the only concern. Leukemia specialists are starting to test patients for another enzyme deficiency that makes the standard dose of a children’s leukemia therapy called mercaptopurine far too high for their bodies.

Also, 50 common drugs occasionally cause a lethal irregular heartbeat. Patients’ hearts first exhibit a rhythm change called “long QT interval” before going into the arrhythmia with the unwieldy name “torsades de points.” Some genes can spur this problem by making drugs 10 times more potent at blocking heart relaxation channels, Woosley said.

His lab just launched an international effort to research survivors and create gene chips to test patients for the risk before they take a new drug. Doctors, or torsades survivors, can check http://www.qtdrugs.org to participate.

Gene chips will take several more years to hit the market. But PPGx and other labs today can find gene-drug interactions through standard, cheap gene-test methods _ they already provide p450 and other enzyme tests for drug manufacturers. Consumers very soon will demand such tests, too, Baker predicts.

“If they shouldn’t take a drug, they should know. I know I would want to know.”
EDITOR’S NOTE _ Lauran Neergaard covers health and medical issues for The Associated Press in Washington.
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