About half of all medical patients get a drug, in any given year, that could interact with their genes and cause serious side effects.
Article: Scientificamerican.com
Inexpensive gene tests, as yet only available in a few hospitals, could avoid these life-threatening problems. Yet lack of insurance reimbursement and confusion over when and how to alter drug prescriptions hold back tests’ widespread use.
Korei Parker is a boisterous seven-year-old with an infectious smile who improvises her own songs and loves to share them out loud. On an April day two years ago ago in Memphis, Tenn., where she lives, Korei came home from school with strange bruises. She had bumped into some things, she said—maybe a desk—but not hard enough to cause deep marks. Her mother, Rhonda, called their pediatrician and set up an appointment for later that week. But the next morning Korei woke up with new splotches across her arm and forehead. And when Korei brushed her teeth, her gums started to bleed.
Mother and daughter rushed to nearby St. Jude Children’s Research Hospital. Doctors there figured out Korei was not producing enough new blood cells, which causes uncontrolled bleeding, bruising and infections. The illness is called severe acquired aplastic anemia.
The girl was quickly put on several drugs to boost her blood cells and fight infections. St. Jude doctors also did something unusual: They tested Korei for some 230 genes that affect which drugs—and what doses—would work best in her body. Certain gene variants can trigger the body to break down medications very quickly. In such cases, even high drug doses may fail.
Because of her particular genetics, the tests showed, Korei broke down voriconazole—a drug doctors had initially prescribed to stave off fungal infections—too fast. “She took adult dosages, and it didn’t seem to do anything for her,” Rhonda says. Her daughter had not contracted a dangerous fungus yet, but she was vulnerable, and her body would not be able to fight back. So physicians switched to another drug that interacts with bodily enzymes made by different genes. Korei’s body processed that drug normally, and she remained infection-free.
Tailoring treatments to genetic makeup is part of the futuristic vision of personalized medicine, where all care is custom-fit to an individual’s DNA. Remarkably, part of that vision—genetic drug matching, called pharmacogenomics—is already here. Korei Parker benefited from it. Although total human genome sequencing costs $1,000, getting drug-gene results on a few hundred genes at St. Jude costs about half that much for each patient. “The era of precision medicine is upon us,” says Dan Roden, assistant vice chancellor for personalized medicine at Vanderbilt University Medical Center. “The low-hanging fruit here is pharmacogenomics.”
Unfortunately this fruit is being plucked by only a handful of hospitals. Lack of insurance coverage for the tests, along with confusion among doctors about what to do with the genetic data, is preventing the exams from being widely used.
The sad result, advocates say, is that people are getting sick needlessly. Between 5 and 30 percent of the global population is estimated to have the same troublesome gene variant as Korei, for example, and it affects how well people respond to multiple medications, not just voriconazole. Roughly 50 percent of hospital patients get a drug in any one-year period that could cause serious side effects because of that person’s genetic makeup, according to analyses from St. Jude and Vanderbilt. One study at Vanderbilt, which examined only six drugs, estimated that drug-gene tests could eliminate some 400 adverse events in a patient population of 52,942. If tests were performed for more than six drugs across the U.S. population, that number of avoided ailments would likely climb into the hundreds of thousands.
Doctors are not accustomed to making medication choices using genetics. What they have done, for decades, is to look at easily observed factors such as a patient’s age and weight and kidney or liver functions. They also considered what other medications a patient is taking and any personal preferences.
If clinicians would consider genetics, here is what they could learn about prescribing the common painkiller codeine. Typically the body produces an enzyme called CYP2D6 that breaks down the drug into its active ingredient, morphine, which provides pain relief. Yet as many as 10 percent of patients have genetic variants that produce too little of the enzyme, so almost no codeine gets turned into morphine. These people get little or no help for their pain. About 2 percent of the population has the reverse problem. They have too many copies of the gene that produces the enzyme, leading to overproduction. For them, a little codeine can quickly turn into too much morphine, which can lead to a fatal overdose.
These types of drug-gene interactions explain some long-standing medical mysteries. As early as 510 B.C. Greek mathematician Pythagoras (of geometry-class fame) found that when some people ate a particular type of bean they would get hemolytic anemia, a potentially deadly condition in which red blood cells are destroyed and removed from the bloodstream. Some 2,500 years later researchers discovered why that reaction occurred: these people inherit genetic variants that lead to a deficiency in the production of an enzyme called glucose-6-phosphate dehydrogenase (G6PD). That substance normally prevents red blood cell destruction. That very same genetic variant—which can be spotted with today’s gene tests—also predisposes patients to hemolytic anemia if they take several drugs now on the market, including rasburicase, a medication often given to patients with leukemia.
Many such drug-gene interactions—both severe and subtle—could be avoided by taking different doses of the drugs or turning to substitutes. Researchers concluded in October 2015 in Nature that there are 80 medications—affected by about two dozen genes—with known alternative treatments.
PGx Medical works with healthcare providers across the country educating and implementing pharmacogenomic testing in long term care communities. There is no cost for patients on medicare b and the test can help eliminate unnecessary medications and potentially harmful drug interactions. For more information, or to schedule a speaker or training on how to implement the test in your facility, contact: info@pgxmed.com or call 405-509-5112.
source: scientificamerican.com