Post by Mayleng on Dec 30, 2004 14:03:34 GMT -5
I had typed this article to answer some questions on Genetic Testing for the Strattera metabolizing Gene. I thought it might be of interest to some others as it relates to other meds as well. Here's the article:
Making Medicine SAFE
By Rob Waters (May 2004)
Several months ago, 11 yr old Hillary DeSmarais of Fort Worth, Texas, attended a party in her honor. People brought presents, laughed, and gave the healthy girl hugs. It wasn't her birthday; the party was at a hospital. At the age of 6, Hillary had been diagnosed with acute lymphoblastic leukemia.
Hillary could easily have lost her battle with cancer. Not because she didn't get good care: Her doctors acted quickly, putting her on a cocktail of powerful chemotherapy drugs. This treatment helps cure some 80% of leukemia patients. But one of the drugs, mercaptopurine, can produce toxic effects.
After a few weeks of treatment, Hillary's white blood cell counts had dropped so low that she had virtually no immune system. Her doctors had to stop treatment to let her immunity recover, and so began a terrible dance for the little girl: Hillary wuld be on the drugs for two to three weeks, and her white blood cell count would plummet. Then she'd go off for a week to give her immunity a chance to return. "It was scary", says her mother, Araceli, a pediatric nurse. "Everytime she went off treatment, she'd get leg pain. I kept thinking it was cancer in her bone marrow."
Three frightening months later, Hillary finally caught a break. Her doctor called William Evans, research director at St. Jude Children's Hospital in Memphis. Evans had helped uncover a genetic breakthrough: One in ten Americans have a bad version of a gene that produces the enzyme called TPMT. This enzyme helps break down certain drugs, including mercaptopurine. People with bum copies of the gene have virtually no TPMT. "When they take mercaptopurine," explains Evans, "it's as if you're giving them up to ten times too much."
Sure enough, a blood test showed that Hillary had a bad copy of the gene. Her dosage was slashed, and she remained on finely tuned doses of mercaptopurine for two & half years. Last December at her party, Hillary was celebrating five years of being cancer-free - the official definition of a survivor.
Hillary DeSmarais is among a growing number of people who are reaping the benefits of pharmacogenomics, a new field of personalized medicine. Because of their genes, people like Hillary are uniquely sensitive to certain drugs: for others, those same drugs have little effect. The promise of personalized medicine is that by testing a patient's DNA, doctors will be able to identify these genetic variations. "You can lower the dose of the drug, you can raise it or you can avoid it altogether," says Richard Weinshilboum, a professor of molecular pharmacology at the Mayo clinic and a leading pharmacogenomic researcher. "This is one of the first places where the genomic revolution is having an impact on medical practice."
DEADLY DOSES
An estimated 106,000 Americans die each year due to adverse reactions to medications, according to most recent research. consider: Nearly half of all drugs on the market - including painkillers such as codeine, cholesterol-lowering statins, and anti-depressants such as Prozac and Paxil are processed by enzymes controlled by a family of genes known as CYP450.
Mutations in these genes can have very different results. Some people have multiple copies of a gene called 2D6. Dubbed "supermetabolizers," these people will, for instance, get no relief from codeine because it's broken down so fast it has no effect. Others - more than 15 million Americans - have two bad copies of 2D6, making them poor metabolizers. This was the case for 9 yr old Michael Adams-Conroy, who suffered from Tourette's syndrom and obsessive compulsive disorder. He was put on Prozac, but his body was unable to metabolize the drug, which built up toxic levels. He eventually had a seizure and died. His genotype was learned only after his death.
"If you are taking Paxil or Prozac and you're one of the 7 of 100 people, you're going to build up high levels of drug in your system," says David Mrazek, a child pyschiatrist who chairs the department of pyschiatry and psychology at the Mayo Clinic in Rochester, Minnesota. "If you're an adult, you'll normally stop taking it because you'll have headaches and be sick to your stomach. But if you're a 6 yr old and you've been told to take this drug, it's tougher to say. "No, I feel lousy. I'm not going to take it"."
THE GENE SCREEN
Mrazek's clinic can now test patients who are candidates for Prozac and other antidepressants. thanks to a device called a genetic chip, Mrazek can identify with 99.99 percent certainty the form of the gene people have and thus how well they'll be able to metabolize the drug.
"What we've done in the past is to try to choose a medication that we believe wil be helpful and then watch and see what happens. And if there is a bad reaction, we try another." Mrazek says. "There are now 23 different medications that can be used to treat depression - it's a staggering number." Using this trial and error process, he says, it could take months to find the right medication."
STOP THE BLEEDING
Wafarin is one of the 20 most commonly prescribed drugs in the country. Every year, some two million patients take it to prevent blood clotting an stroke. But about 40,000 of them develop major bleeding. "It's an effective drug," says Brian Gage, associate professo of medicine at Washington University in St. Louis. "But if you get too much, it can kill you."
Nearly one-third of Americans have a variation of a gene (known as 2C9) that causes them to be poor metabolizers of the drug. According to a 2002 study, these people are nearly two and a half times as likely to sufer serious, life-threatening bleeding.
In another study of 369 warfarin patients published in January, Gage and his olleagues concluded that by testing patients in advance and adjusting their dosage, they could reduce the number of potential overdoses from 16 percent down to 6.5 percent. "There are hundreds to thousands of this variation. They could be prevented if patients were genotyped." Gage says.
PRIME TIME
As pharmacogenomic knowledge advances, regulators at the Food and Drug Administration are wrestling with the type of testing they should require from drugmakers, and the information they want drug companies to provide to doctors and patients. In 2002, Strattera, a new drug for attention deficit/hyperactivity disorder, became the first drug with a message on it's label informing doctors they could test patients to determine their version of the 2D6 gene.
Last year, an advisory committee to the FDA recommended that such information be aded to the label for mercaptopurine. This would not only benefit leukemia patients, whose doctors are now generally aware of the genetic issues, but also patients who suffer from Crohn's disease, a much more common ailment that is often treated with a similar drug.
Making Medicine SAFE
By Rob Waters (May 2004)
Several months ago, 11 yr old Hillary DeSmarais of Fort Worth, Texas, attended a party in her honor. People brought presents, laughed, and gave the healthy girl hugs. It wasn't her birthday; the party was at a hospital. At the age of 6, Hillary had been diagnosed with acute lymphoblastic leukemia.
Hillary could easily have lost her battle with cancer. Not because she didn't get good care: Her doctors acted quickly, putting her on a cocktail of powerful chemotherapy drugs. This treatment helps cure some 80% of leukemia patients. But one of the drugs, mercaptopurine, can produce toxic effects.
After a few weeks of treatment, Hillary's white blood cell counts had dropped so low that she had virtually no immune system. Her doctors had to stop treatment to let her immunity recover, and so began a terrible dance for the little girl: Hillary wuld be on the drugs for two to three weeks, and her white blood cell count would plummet. Then she'd go off for a week to give her immunity a chance to return. "It was scary", says her mother, Araceli, a pediatric nurse. "Everytime she went off treatment, she'd get leg pain. I kept thinking it was cancer in her bone marrow."
Three frightening months later, Hillary finally caught a break. Her doctor called William Evans, research director at St. Jude Children's Hospital in Memphis. Evans had helped uncover a genetic breakthrough: One in ten Americans have a bad version of a gene that produces the enzyme called TPMT. This enzyme helps break down certain drugs, including mercaptopurine. People with bum copies of the gene have virtually no TPMT. "When they take mercaptopurine," explains Evans, "it's as if you're giving them up to ten times too much."
Sure enough, a blood test showed that Hillary had a bad copy of the gene. Her dosage was slashed, and she remained on finely tuned doses of mercaptopurine for two & half years. Last December at her party, Hillary was celebrating five years of being cancer-free - the official definition of a survivor.
Hillary DeSmarais is among a growing number of people who are reaping the benefits of pharmacogenomics, a new field of personalized medicine. Because of their genes, people like Hillary are uniquely sensitive to certain drugs: for others, those same drugs have little effect. The promise of personalized medicine is that by testing a patient's DNA, doctors will be able to identify these genetic variations. "You can lower the dose of the drug, you can raise it or you can avoid it altogether," says Richard Weinshilboum, a professor of molecular pharmacology at the Mayo clinic and a leading pharmacogenomic researcher. "This is one of the first places where the genomic revolution is having an impact on medical practice."
DEADLY DOSES
An estimated 106,000 Americans die each year due to adverse reactions to medications, according to most recent research. consider: Nearly half of all drugs on the market - including painkillers such as codeine, cholesterol-lowering statins, and anti-depressants such as Prozac and Paxil are processed by enzymes controlled by a family of genes known as CYP450.
Mutations in these genes can have very different results. Some people have multiple copies of a gene called 2D6. Dubbed "supermetabolizers," these people will, for instance, get no relief from codeine because it's broken down so fast it has no effect. Others - more than 15 million Americans - have two bad copies of 2D6, making them poor metabolizers. This was the case for 9 yr old Michael Adams-Conroy, who suffered from Tourette's syndrom and obsessive compulsive disorder. He was put on Prozac, but his body was unable to metabolize the drug, which built up toxic levels. He eventually had a seizure and died. His genotype was learned only after his death.
"If you are taking Paxil or Prozac and you're one of the 7 of 100 people, you're going to build up high levels of drug in your system," says David Mrazek, a child pyschiatrist who chairs the department of pyschiatry and psychology at the Mayo Clinic in Rochester, Minnesota. "If you're an adult, you'll normally stop taking it because you'll have headaches and be sick to your stomach. But if you're a 6 yr old and you've been told to take this drug, it's tougher to say. "No, I feel lousy. I'm not going to take it"."
THE GENE SCREEN
Mrazek's clinic can now test patients who are candidates for Prozac and other antidepressants. thanks to a device called a genetic chip, Mrazek can identify with 99.99 percent certainty the form of the gene people have and thus how well they'll be able to metabolize the drug.
"What we've done in the past is to try to choose a medication that we believe wil be helpful and then watch and see what happens. And if there is a bad reaction, we try another." Mrazek says. "There are now 23 different medications that can be used to treat depression - it's a staggering number." Using this trial and error process, he says, it could take months to find the right medication."
STOP THE BLEEDING
Wafarin is one of the 20 most commonly prescribed drugs in the country. Every year, some two million patients take it to prevent blood clotting an stroke. But about 40,000 of them develop major bleeding. "It's an effective drug," says Brian Gage, associate professo of medicine at Washington University in St. Louis. "But if you get too much, it can kill you."
Nearly one-third of Americans have a variation of a gene (known as 2C9) that causes them to be poor metabolizers of the drug. According to a 2002 study, these people are nearly two and a half times as likely to sufer serious, life-threatening bleeding.
In another study of 369 warfarin patients published in January, Gage and his olleagues concluded that by testing patients in advance and adjusting their dosage, they could reduce the number of potential overdoses from 16 percent down to 6.5 percent. "There are hundreds to thousands of this variation. They could be prevented if patients were genotyped." Gage says.
PRIME TIME
As pharmacogenomic knowledge advances, regulators at the Food and Drug Administration are wrestling with the type of testing they should require from drugmakers, and the information they want drug companies to provide to doctors and patients. In 2002, Strattera, a new drug for attention deficit/hyperactivity disorder, became the first drug with a message on it's label informing doctors they could test patients to determine their version of the 2D6 gene.
Last year, an advisory committee to the FDA recommended that such information be aded to the label for mercaptopurine. This would not only benefit leukemia patients, whose doctors are now generally aware of the genetic issues, but also patients who suffer from Crohn's disease, a much more common ailment that is often treated with a similar drug.
