Talk

With the recent FDA’s activity in personalized medicine, I asked DNA Direct’s director of pharmacogenetics, Dr. Huijun Z. Ring, if she’d give us a guest post.

Huijun writes:

FDA warns breast-feeding moms of genetic risk for using codeine products
Gene test can help to prevent life-threatening side effects in nursing babies

When I was home with my first baby, my training in science and medicine went out the window, and I found myself to be as much of a novice as every other new mother. I wanted to make sure that everything was perfect. Mostly, however, our family went forward by trial and error, learning as we went along how to care for our new member. Gratifyingly, a recent advance in my field of pharmocogenetics will help remove one uncertainty for mothers.

Codeine is a frequently used medication for mothers after child birth and for infants in their first year life. On Aug 17, the FDA issued a Public Health Advisory warning that a rare, but sometimes life-threatening, side effect of codeine in nursing babies could be attributed to a mother’s genetic makeup. (more…)

MSNBC provides compelling statistics about how genetic testing for warfarin (Coumadin) dosage can make a difference:

FDA economists estimate the genetic testing could prevent 85,000 “serious bleeding events” and 17,000 strokes a year, according to a November 2006 study posted to the Web site of the American Enterprise Institute. The savings to the health care system could be $1.1 billion a year, though some people question that. The genetic tests can cost $125 to $500. About 2 million people start taking the drug each year.

Warfarin sends more than 43,000 people to the emergency room each year, the FDA economists said. That total is more than for any other drug except insulin, which diabetics use.

The Washington Post has a suprisingly brief article, pointing out that

Studies have shown that the risk of a serious bleeding episode — into the brain or intestine, for instance — is highest soon after treatment has begun.

Technorati Tags: warfarin, coumadin, genes, genetic test, fda, label, risk, blood thinner, cost

Yesterday the FDA announced a new label for the blood thinner, Coumadin (generic: warfarin). The new label explains that people’s genetic makeup may influence how they respond to the drug, and that a $300-500 genetic test can help physicians tailor the drug dose to increase effectiveness and reduce the serious risk of bleeding.

The FDA says:

Warfarin is a difficult drug to use because the optimal dose varies and depends on many risk factors including a patient’s diet, age, and the use of other medications.

Patients who take a dose larger than they can tolerate are at risk of life-threatening bleeding. Those who receive too low a dose are at risk of equally dangerous blood clots. Dosing is particularly important at the beginning of therapy, when problems in adjusting the dose can lead to complications such as bleeding. …

A person’s genes “encode” enzymes and differences in the sequence of a gene can cause differences in enzyme activity or sensitivity. That is why different people process the same drug differently.

Good news, right? Another example of personalized medicine and how it can revolutionize patient care. Unfortunately the wheels of the machine grind slowly, and defensively. So it will be interesting to see how quickly this testing becomes routine: Will it become routine in top medical centers first, as new technology often is? Or, will Medicare bite at the potential for significant emergency room savings by making the gene test mandatory before prescribing warfarin, a drug so common in their population. (more…)

When I was in grade school in the 1970s we celebrated the bicentennial of the United States. In my memory, it was the biggest, longest birthday party ever. A big theme in our studies before and during 1976 was the US as the “Great Melting Pot” — of people, of languages, of cultures. Schoolhouse Rock even provided the illustrations.

Now it’s the 2000s and, guess what, I’m still talking about the melting pot phenomenon with colleagues. But this time, it’s the melting pot analogy* applies in terms our genes:

“Pharmacogenetics/genomics has the potential to benefit people worldwide and to reduce the health disparities between developing and developed nations. This goal is unlikely to be achieved by relinquishing the notion of personalized drug therapy tailored to individual genetic characteristics–the original promise of pharmacogenetics–in favor of a model (pharmacogenomic?) of population-based drug development and prescription, with all its potential pitfalls, especially when extended to admixed populations in developing or developed nations.”

(more…)

The Washington Post has an unusually lengthly article on DNA testing to determine warfarin dosing. Recently, I blogged about the launch of this testing: “Warfarin Sensitivity Test Launches.”

Warfarin (brand name Coumadin) is a popular blood-thinning medication used by about 2 million Americans. It’s prescribed after surgeries, strokes, blood clots, and to prevent blood clots. Medco Health Solutions and the Mayo Clinic are collaborating on a project using this testing to determine initial dosing for patients.

Epstein and other experts say the warfarin projects comprise the first broad use of personalized medicine, or targeted therapy, in which a person’s genetic makeup is used to pick the best medicine or dose. This approach essentially adjusts for differences in body chemistry that explain why one pain reliever or allergy pill works great for you but not for your mom. … (more…)

Happy new year, everyone! I just returned from an unusually exciting break (more on that in later posts) to find that genetic testing is the cover story of this week’s US News & World Reports:

Unraveling Your DNA’s Secrets: Do-it-yourself genetic tests promise to reveal your risk of coming down with a disease. But do they really deliver?

Also, you can now listen to public radio’s December 21 Health Dialogues’ program online:

Genes, Disease and Difference

The program begins with the story of a woman who pursued genetic testing for tamoxifen efficacy, but the panel discussion is wide-ranging, with perspectives from all over the industry.

Technorati Tags: news, dna, genetic testing, disease risk, tamoxifen, media coverage

I’d say that this year’s stories ran the spectrum from “what’s in our genome?” to “what does it say about us?” to “what should we do with that information?” Yes, here’s science to policy in six easy pieces!

Diabetes Risk Genes Are Confirmed. The body of research behind this discovery is impressive, covering populations around the world and all hitting publication in a very short window of time. (I think Denise Grady, a health journalist at the New York Times captured this best with the context of a personal perspective.) With news about Americans’ skyrocketing diabetes rates, our overweight children, and our heaviest nation status, you’d think this genetic news would have made a bigger splash. Stay tuned in 2007 and let’s see what happens once testing becomes available.

The FDA Recommends Relabeling Tamoxifen - In October, the FDA met to review a compelling body of research that shows 7-10% of people may not receive medical benefit of tamoxifen, because of their 2D6 genes. This is an historic first for pharmacogenetics: it’s the first time FDA has recommended relabelling for the effectiveness of a drug, not just toxicity warnings (e.g. atomoxetine/Strattera for ADHD). It’s also notable that certain SSRIs, particularly Paxil, interfere with the metabolism of tamoxifen just like these genes do - so taking both Paxil and tamoxifen effectively cancels out the benefit of the tamoxifen. Please indulge me as I proudly say that my company is on the ball - we began providing this genetic test to consumers and doctors in October, right after the FDA’s recommendation came out.

(more…)

Since DNA Direct first began offering CYP2D6 testing for tamoxifen efficacy last month, we’ve had calls from women asking, “how come my doctor didn’t recommend this?” and “why doesn’t my doctor know about this?”

Dr. Kevin Knopf, a respected medical oncologist who specializes in breast cancer, has an explanation in his post this week “Something to Worry About? Tamoxifen Effectiveness.” He wrote this post upon first learning about tamoxifen and 2D6 — from his newspaper. He says:

It is also interesting how oncologists and other doctors find out about news this big – were it not for my newspaper I don’t know when it would first come to my attention (I’ll let you know next month!) When I asked my partner if he had heard about it, it was news to him. There are often no “mass broadcasts” of “breaking news” –e.g. nothing on my email yet. So this can create anxiety for patients who might see something before their oncologist does. I think the best approach would be to let the information get absorbed prior to making any decisions about tamoxifen and to seek guidance from your personal oncologist.

(more…)

Copy Number Variation in Our Genome. Over at Evolgen, RPM explains “recent work indicates that there’s also quite a bit of variation amongst individuals in the actual content of their genomes. Such variation is known as copy number variation (CNV) or copy number polymorphism (CNP). What it means is that some people may have one copy of a genomic region, other may have two, and even others may have none.” What does this actually mean? Read RPM’s commentary and Hsien’s explanation. Or, read Reuters’ boiled-down news. Or, check out Nature’s accessible but detailed article.

Proof is Scant on Psychiatric Drug Mix for Young. Many psychiatrists and parents believe that drug combinations or “cocktails” help for conditions such as ADHD. There’s a lot to be debated about this, and when it comes to children, all our concerns about drug risks are amplified. Studies in children are fewer, children’s bodies and minds are evolving, and children don’t usually get to choose for themselves. What do you think? (more…)

The only recent coverage I’ve seen so far about the FDA’s relabeling of tamoxifen on is from the PGx Reporter, which is subscription-only. Here’s their public excerpt:

FDA Panel Leans Toward Including CYP2D6
Dx in Tamoxifen Label, But is Split on Language

The Pharmaceutical Science Clinical Pharmacology Subcommittee was split over whether the label should “recommend” the genetic test or make it an “option” for health care providers and patients to discuss.

As it considers just how strong the wording on the label should be, the FDA is looking at the role of endoxifen (the active metabolite), 2D6, and drug interactions.

We’re getting many inquiries ourselves into the Tamoxifen 2D6 Test. Here are recently asked questions and answers, and previous posts on Tamoxifen and 2D6 Testing.

Technorati Tags: tamoxifen, cyp2d6, genes, drug metabolism, fda recommendation, drug interactions, genetic test, dna

Have you had a blood clot or DVT? If so, chances are you’ve been on warfarin (brand name: Coumadin). Warfarin, a blood-thinner, is the most commonly prescribed drug for preventing and treating blood clots.

Warfarin is also known to be a difficult drug to manage, for two reasons. First, the blood levels in which warfarin is effective are very narrow, which means doctors need to carefully calibrate the dose. Secondly, people have a wide range of responses to it, which means calibrating the dose is more challenging.

Kimball Genetics (a laboratory) has just launched a genetic test for warfarin sensitivity, which better predicts an individual’s response to warfarin. This test can help your doctor determine the warfarin dosage that’s best for you — lowered risks, maximum effectiveness. (more…)

I just returned from vacation to find a great article in National Geographic about how genomics is - and will increasingly - affect the practice of medicine: Personalized Medicine Promises Tailor-Made Diagnoses, Treatments

Here’s a clip to encourage you to go check it out:

The genetic variations can be used to identify susceptibility to a particular disease and to pinpoint targets for drug treatments.

Currently drug courses are often ineffective. Physicians may have to prescribe several different treatments before identifying one that works.

“Personalized medicine is about changing the medical paradigm,” said Edward Abrahams, executive director of the Personalized Medicine Coalition in Washington, D.C. “It promises to replace trial-and-error medicine with a more targeted get-it-right-the-first-time approach.”

(more…)

Widespread Study - Adverse Drug Reactions. A study developed by the CDC, FDA and Consumer Product Safety commission shows that harmful reactions to medicines send more than 700,000 Americans to emergency rooms each year. Over 700,000. to the emergency room. The study’s authors and other experts agree that this number is probably low because bad drug reactions are also likely to be misdiagnosed. This is yet another reason why PGx testing can revolutionize medicine.

New Gene May Help Predict and Treat Chronic Pain. People who have a certain gene variant are at lower risk of developing severe chronic pain and are less sensitive to painful stimuli, researchers report. Besides the potential for diagnosing the risk of chronic pain, the discovery offers a starting point for identifying new painkillers.

Portraits of an Artist with Alzheimer’s. A talented artist throughout his life, William Utermohlen provided a window into the experience of Alzheimer’s from the individual’s perspective. While there are some genetic markers associated with Alzheimer’s, their relationship isn’t fully mapped out yet and so testing for risk isn’t ready for prime time. While DNA Direct often receives calls from people wanting “a genetic test for Alzheimer’s”, we don’t offer testing for multiple reasons (see the comments below this post).

In Case of Emergency: ICE Your Cellphone. To aid emergency workers, doctors are encouraging people to add an “ICE” contact into their cellphones. ICE stands for “in case of emergency” and provides emergency workers with a way to find your nearest and dearest, as quickly as possible, should you be unable to communicate with them. Everyone, go program your phones now!

Technorati Tags: adverse drug reactions, side effects, medication, statistics, genes, pgx, pharmacogenetics, painkillers, chronic pain, alzheimer’s disease, ice

Ryan (the CEO and founder of DNA Direct) and I just returned from an FDA meeting where members of the Clinical Pharmacology Subcommittee, a group composed of doctors and researchers, made an important decision about the breast cancer drug tamoxifen. As Lisa Lee described last week, the purpose of this meeting was to decide whether to recommend changing the tamoxifen package insert, also known as the drug label, to include information about how the 2D6 gene is a predictor of response to tamoxifen.

Clearly the decision of the Subcommittee is a historic moment, both for the emerging field of pharmacogenetics (or how genes influence a patient’s response to drugs) and, most importantly, for the breast cancer community. After all, hundreds of thousands of women are on the drug tamoxifen, and more women are put on the drug every day. The fact that some of them may not be receiving full benefit from tamoxifen because of their genes — therefore increasing their risk of cancer recurrence — could not be more important for breast cancer patients to know about.

So, what did the Subcommittee recommend? (more…)

Speaking of breast cancer - we’re on a roll this month! - there are very important happenings at the FDA next week. On October 18, the FDA will to evaluate recent research regarding 2D6 gene variants and response to the breast cancer drug, tamoxifen, and whether this research warrants any warnings or changes to the tamoxifen package insert.

Here’s a link to the FDA’s Executive Summary on Tamoxifen and 2D6. (Clicking this link will download a .PDF.)

In concert with the hearing, DNA Direct is launching our first drug metabolism test: 2D6 testing with personalized test results interpretation for tamoxifen. (Testing can be ordered online at the Genes&Drugs website.) Below is DNA Direct’s backgrounder, which explains the test, the research and why we’re offering 2D6 Tamoxifen testing to certain patient populations.

TAMOXIFEN & 2D6 BACKGROUNDER

Recent research on tamoxifen has shown that potentially up to 7-10% of women with breast cancer may not receive the full medical benefit from taking tamoxifen, because of their unique genetic make-up. These women have a special version of a gene (CYP2D6, commonly referred to as 2D6), which may reduce the effectiveness of tamoxifen and increase their chance of breast cancer recurrence. With over 500,000 women currently taking tamoxifen, this research has wide-reaching implications. (more…)

I’ve been looking for something other than breast cancer to talk about since I just posted on hereditary breast and ovarian cancer, because September was Ovarian Cancer Awareness Month…but I can’t avoid it. Everyone’s wearing pink ribbons and news about breast cancer abounds:

• A new breast cancer gene has been found: BRIP1.
• The White House issued an official proclamation by the President that October is National Breast Cancer Awareness Month.
• The FDA is meeting next week to discuss tamoxifen, a drug metabolism gene called CYP2D6, and their relationship in terms of risk for breast cancer recurrence.

Stay tuned for more info on the FDA hearing next week….

Technorati Tags: breast cancer, hereditary cancer, genes, brip1, tamoxifen, drug metabolism, breast cancer recurrence

In “The Graduate,” Dustin Hoffman’s character is told that the promise of the future can be summed up in one word: plastics. Well, we’re now clear on the word for 2007: pharmacogenetics.

Today’s must-read article is a short interview with Dr. Mary V. Relling, head of the department of pharmaceutical sciences at St. Jude Children’s Research Hospital, by Claudia Dreifus. Here’s a taste:

Q. How is this tailoring of drugs different from the way they’re currently ordered?

A. Till now, there’s been a one-size-fits-all approach. In most cases, an average dose of a medication is ordered, and then, if the patient suffers side effects, the dosage is adjusted. With gene testing, we can customize the prescription….

Dr. Relling explains why she travels the country advocating its use — “We’ve seen it save lives here. That’s made me a believer.” — and discusses the growth of the field, how it can change medicine, and what this may mean for pharmaceutical companies.

Technorati Tags: pharmacogenetics, PGx, medication, drugs, genetic testing

Today brings good news for my colleague Jason, the man with the high-octane coffeepot. Earlier this year, research into the pharmacogenetics of caffeine metabolism had him a bit wound-up. But today Jason can pour himself another cup as he ponders the latest news: Researchers have found strong evidence that coffee reduces the risk of several serious ailments, including diabetes, heart disease and cirrhosis of the liver. Yes, coffee even has antioxidents!

Rob van Dam, a scientist at Harvard and author of a review of studies into coffee and risk for diabetes, acknowledges that caffeine could possibly raise the risk for heart disease (by increasing blood pressure and slightly increasing homocysteine levels). But as he tells the New York Times,

I wouldn’t advise people to increase their consumption of coffee in order to lower their risk of disease … but the evidence is that for most people without specific conditions, coffee is not detrimental to health. If people enjoy drinking it, it’s comforting to know that they don’t have to be afraid of negative health effects.

Cheers, java lovers!

(For the non-coffee crowd: have you heard the tasty news about hot chocolate?)

Technorati Tags: pharmacogenetics, caffeine, metabolism, coffee, heart disease, liver disease, diabetes, risk, health benefits, hot chocolate

In the midst of all this talk about genes, drugs and genetic testing comes a brand new blog called — you guessed it! — Genes & Drugs. I’m pleased to announce the launch of this new blog by Dr. Alan Eshleman. While we muse over what the latest news on pharmacogenetics might mean for patients, Dr. E will be talking about the ins and outs of PGx for physicians and other healthcare professionals.

Dr. E has a long history of contributing to online and offline communities. For many years he moderated health & medical communities at The Well. More recently, he wrote “Doctor E’s Diary” for the San Francisco Chronicle’s online site.

If you are as excited about the promise of pharmacogenetics as I am, you’ll want to check in regularly with Dr. E.

Technorati Tags: genes, drugs, drug metabolism, genetic testing, Alan Eshleman, PGx

I am thrilled to see discussion in today’s NY Times about the promise of genetic testing for drug metabolism. In particular, I’m excited to see mainstream media discussion of tamoxifen efficacy and genotype.

Much has been made of research published in the past few months regarding aromatase inhibitors — to what degree they prevent breast cancer recurrence, long-term survival, overall survival, and to what degree they’re better than tamoxifen (current studies indicate ~2-3%). That’s very exciting.

What you’re not hearing about, and which could take treatment decision-making to a higher level, is research into gene variants that may indicate who is likely to respond to tamoxifen and who isn’t. This could alter what we’ve previously thought of as tamoxifen efficacy rates. Gina Kolata explains and quotes Dr. David Flockhart, a leading researcher in this area:

(more…)

Some women carry multiple copies of a gene that metabolizes codeine into morphine. These women process codeine at much higher rates than the average person, which means that when they take an average dose of codeine, it is rapidly converted to unusually high levels of morphine.

For new mothers prescribed codeine after childbirth, this can be a tragic cocktail for their babies. A recent study in Canada reports the death of a newborn from morphine overdose via breast milk.

Babylune notes, “This is not a reason to stop nursing. This is a reason to stop taking codeine.” I say it’s also a reason to consider genetic testing for drug metabolism.

The gene involved in codeine metabolism is called CYP2D6. It metabolizes around 25% of all commonly prescribed medications. It’s also involved in the metabolism of some over-the-counter meds, herbal supplements, and even some foods. Knowing your genetic status is useful information if you’re prescribed or considering taking any drugs metabolized by CYP2D6.

Our company will soon be offering drug metabolism testing — and you can be sure I’ll be the first in line for it. Stay tuned!

Technorati Tags: codeine, morphine, breast milk, breastfeeding, painkillers and breastfeeding, medications and childbirth, CYP2D6, drug metabolism, genes, genetic testing

At a baby shower this weekend, I had one of my two regular party conversations. Someone says, “Genetic testing? Cool! Do you do all that CSI stuff?”

No, I don’t wield big flashlights and hang around crime scenes. DNA can tell more than one interesting story. In addition to forensics, DNA technology is used for…

Predispositional Tests. These tests can give you permanent, life-long insight. They look at your genetic makeup to see if you carry a gene that puts you at higher risk for a certain disease. This type of testing can also be used to confirm a diagnosis, or determine whether a condition you already have is genetically based.

Screening Tests. Similar to X-rays or other tests that record a moment in time, these tests look at a cell sample for “acquired” DNA mutations (not inherited) that can indicate whether a disease, such as cancer, is present in a part of the body.

Paternity Tests. This type of testing looks at the DNA of a mother, child, and the man thought to be the child’s father, to see if the man is indeed the biological father of the child.

Ancestry Tests. These tests look at your Y chromosome (men only) and mitochrondrial DNA for specific genetic markers that are unique to certain populations. These markers indicate your deep ancestry migration patterns, and thus, genetic ethnicity. (Have I raved about the Genographic Project yet?)

Drug Metabolism Tests. These tests tell you how quickly your body processes certain types off drugs, and whether or not you are likely to experience side effects or toxicity. For some drugs, testing will tell you whether the drug in question will be effective.

So what’s the other party question? “Can you test my dog to see what breeds he’s made of?” (No, not yet :-))

Thank you, Gina Kolata, for continuing to explain both the science and the personal dilemmas of breast cancer treatment research.

Increasingly, oncologists and researchers are focusing on the nature of the tumor itself — “tumor typing” — rather than the location of the tumor when recommending treatments. I expect that very soon, we won’t be diagnosed with “breast cancer.” Rather, we may have “estrogen-receptor positive, HER2/neu amplified, TOP2A amplified cancer located in the breast.”

In addition to HER2 status, estrogen and progesterone receptors, there are other biomarkers currently under study that may help us make treatment decisions.

Genes may also tell us about whether or not we will respond to the treatments indicated by tumor typing. Research is mounting that the effectiveness of tamoxifen depends on which versions of the CYP2D6 gene you inherit.

Stay tuned for more posts on genes and drugs, aka, pharmacogenetics. And a hat tip to Hsien for her latest post on genes and cancer risk.

Update: Read more current posts about tamoxifen here. Also, DNA Direct now offers 2D6 testing for tamoxifen response.

Technorati Tags: breast cancer, treatment, tamoxifen, genes, pharmacogenetics, CYP2D6

There’s a dramatic piece in the Washington Post today about how genetic testing can predict whether a person will process certain medications, or experience side effects. The Mayo Clinic has been using these tests, particularly with children and people with family histories of bad side effects. But this testing hasn’t hit mainstream usage…yet.

These genetic tests identify how you process certain liver enzymes.

“The most important liver enzymes in drug metabolism are the ones in the ‘cytochrome P450′ (CYP) family. They process 25 percent of all drugs, including those that cause the most adverse reactions — antidepressants, anti-psychotics, painkillers, beta blockers (which slow the heart rate and lower blood pressure) and drugs used to treat attention-deficit hyperactivity disorder (ADHD).

Say you take a drug that is mostly processed by the enzyme CYP 2D6. If your liver produces too much of this enzyme, it could over-process the drug and flush it right out of your body, and you’d get no therapeutic effect. If, on the other hand, your liver produces too little of the 2D6 enzyme or none at all, the drug wouldn’t be sufficiently broken down. Instead, it would build up in your bloodstream. You could overdose on what, for most people, would be a normal dose.”

Had these tests been available a few years ago, my mother could have been spared years of pain, illness and liver damage that resulted from trial-and-error drug regimens. Thankfully, we got her into the Mayo Clinic where she received the diagnoses that had eluded everyone else.

Like many, I believe this testing will become as commonplace as blood typing. It can lead to faster, more effective, more appropriate pharmaceutical treatment - which means better quality of life for people, and cheaper cost of care for insurers.

List of drugs processed by CYP enzymes
How drugs can interact with each other

Technorati Tags: drugs, medications, genes, genetic testing, p450, antidepressants, painkillers, beta blockers, ADHD