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Genetics Provides Hope for Personalized Medicine

Prescribing medication still involves a lot of trial and error. But what if researchers could look at your genes, and figure out what the best medicine was? That's what scientists—including some local researchers—are trying to figure out as part of an emerging field called pharmacogenomics. They're hoping our genes will predict our response to drugs, so they can tailor medications, for conditions like cancer, and ADHD. Chicago Public Radio's Lynette Kalsnes reports as part of a five-part series on genetics.

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ambi: sound of doctor's office.
 
Thirteen-year-old Alex is at the doctor's office. He's getting his blood pressure checked, and his weight for a clinical trial he's in. He has Attention Deficit Hyperactivity Disorder.

ALEX: Sometimes you can be really hyper, and I mean, you don't think you're being hyper, you just think you're being normal, and you don't even realize it, until someone tells you about it.

Alex is a smart kid, with a sharp sense of humor, and an eloquent ability to express himself. Until he gets in school, or in social situations.

ALEX: Sometimes, it's hard to stay focused. You're just thinking one thing, and then you can't concentrate because you're thinking of something else that's more fun or something. So it's hard, ‘cuz when you're trying to take a test or something, and you're thinking about a videogame, you can't get that out of your head until you play it, then you're going to do bad on your test, I guess.

It affects family life, too. His mom, Karen, says she's had to retrain herself as a parent to remember that ADHD is a disorder that her son can't always control.

KAREN: It's a struggle. It can take me an hour to get him physically out of bed. Even if I pick him up and lift him out of the bed, the ability to get moving is just not there.
 
Here's where genetics may offer some hope for Alex and his mom – and families like them. Researchers think about 75 percent of the risk for ADHD is genetic.

So doctors at University of Illinois at Chicago are looking at the DNA of Alex, and hundreds of kids. They want to figure out whether genetics... can help predict the children's response to drugs, and any side effects.

At a UIC clinic, a child psychiatrist meets with Karen and Alex, and asks how Alex is doing.

DOCTOR: Alex have any difficulty organizing tasks or activities? And again it might be trouble with time management, or putting off things to the last possible moment? Yes? He's being honest about that. Act as if he's on the go, or driven by a motor, it's hard to slow down?

ALEX: No.

KAREN: You're not constantly on the go.

ALEX: No.

KAREN: I haven't had to tell you to slow down, or stop and think?

ALEX: No. Sitting on the couch isn't running a marathon. KAREN: But you're not sitting still now.

ALEX: My foot's moving.

The doctor is charting Alex's progress, finding out how he's responding to various drugs, and different dosage levels.

The researchers already know that kids with two short versions of a gene, generally don't do as well on a particular medication, as kids with at least one long version of it. That gene helps send messages through the nervous system.

But those were the results of an earlier, limited study. They need more evidence.

So now doctors are seeing if the results hold true if they include more kids – and different types of drugs. These studies are just a tiny part of an emerging field called pharmacogenomics. So what does that mean exactly?
 
RATAIN: The cliché is to get the right drug, to the right patient at the right dose.

That's Dr. Mark Ratain. He's a leading cancer researcher at the University of Chicago, and heads the university committee that's studying pharmacogenomics.

RATAIN: I think the promise of this field is that we will do a much better job of treating patients. That we will minimize the number of drugs patients are on. We will minimize the number of adverse drug reactions. We will maximize the benefit of drugs.

One of the side effects Alex's been struggling with is insomnia. For the study, he wears a device like a watch that tracks how much he sleeps.

Each week, he and his mom meet with a study coordinator, and today, they're looking at a spiky graphic chart of his sleeping patterns.

KAREN: This is when he fell asleep?

STUDY COORDINATOR: About. Should have been.

KAREN: So it's about 4 o'clock in the morning. Holy cow.

STUDY COORDINATOR: Is that about right?

KAREN: And I thought you probably fell asleep around midnight.

STUDY COORDINATOR: Alex, were there a couple of nights where it seemed like you didn't fall asleep until maybe 3 or 4 in the morning?

ALEX: Yeah.

STUDY COORDINATOR: Yeah.

The psychology professor who's leading the study, Mark Stein, says the current drugs work well for about half the patients. Another 25 percent show some improvement.

But for that last 25 percent or so, the drugs just don't help much at all.

STEIN: The problem with kind of picking the wrong medication, and trying that first, is a certain percentage of people will never try another medicine. They won't get to the second try. That's the worrisome thing.

Quitting medications could have serious consequences for kids like Alex. That's because children who go untreated – or even under-treated – tend to have difficulties in school, relationships and jobs that can continue into adulthood.

And that means in adulthood, says Stein, they're also at risk for:

STEIN: Substance abuse, nicotine use, more frequent emergency room visits. So there's a wide range of impairments associated with ADHD.

The remedy may be far off. The whole field of pharmacogenomics is still in the early stages. There are some genetic tests that can tell if a breast cancer medication won't work, or predict serious reactions to a specific chemotherapy drug.

What Stein and his collaborators are trying to do is add to the base of knowledge. But Chicago-Kent Law Professor Lori Andrews is concerned about the ramifications of this kind of testing. Genetics might tell us too much.

ANDREWS: It may turn out that we learn that you're just a very expensive person to treat, and a potential employer might be interested in that information, a potential insurer.

Another challenge? Finding funding to do the research, says the U of C's Mark Ratain.

RATAIN: These tests are done once in an individual's life. It's not like other diagnostic tests, like even a cholesterol, that you can do every few months. So the potential revenue is relatively limited. And so there's not commercial investment in pharmacogenetics.

There may come a day when drugs are produced for individuals or small groups of people. But those drugs will be costly, says Lori Andrews, because they won't be mass produced.

ANDREWS: If you think pharmacy prices are huge and horrible now, hang onto your hats, because we're going to get into an era where pharmaceutical prices become unaffordable.

Despite these challenges, researchers Ratain and Stein think the promise is greater than the risk.

So do Alex and his mom. He's taking part in the study to help other kids. He has a wish list:

ALEX: I hope that they can make a medication that would help them, so that kids who have ADHD who are on the medication don't have anxieties, and still can have a little fun, but not be totally hyper, and be able to focus on things, even when something else is going through their head. Something that just lets them enjoy life a little better.

Alex says the current medications do help him stay focused. His hope is that someday, pharmacogenomics will do better.

I'm Lynette Kalsnes, Chicago Public Radio.

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