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Heal or Harm? The Truth About Prescription Drugs

Posted on 01/10/2010 12:00am

Prescription drugs meant to make your child feel better may be putting her at risk. Now Canadian researchers are figuring out why - and their work is saving kids' lives

Mark Witten
Originally published in Today's Parent, October 2010

Each of us has about 25,000 genes on 23 pairs of chromosomes. Hayden and Carleton narrowed their three-year search by targeting 300 genes involved in drug metabolism, hoping to find some key ones that were different only in the kids with hearing problems. They discovered two genetic culprits, known as TPMT and COMT. "If a child treated with cisplatin has these gene variants, that child will go partially or completely deaf," says Hayden.

Hayden and Carleton are developing an inexpensive DNA saliva test that would allow doctors to predict who is genetically susceptible. In future, high-risk kids could be offered other treatment options: an alternative chemo drug, lower doses of cisplatin, or a protective drug. Paediatric oncologist Rod Rassekh, who helped identify the gene variants, is now doing a study to see whether a drug called sodium thiosulphate can prevent hearing loss in kids with high-risk genes when administered with cisplatin. The Vancouver researchers are also investigating whether the two genes cause hearing loss in adult patients.

The team is also focusing hard on anthracyclines, a class of drugs given to almost three-quarters of childhood cancer patients. They've helped boost survival rates for kids to over 80 percent, but at a price: possible heart damage. "We've seen kids die because of this," Rassekh says. "One study estimated that the risk of death from cardiac causes was 8.2 times that of the normal population, even 25 years after therapy." Hayden and Carleton have collected DNA from more than 1,400 kids treated with anthracyclines and identified genetic differences in those who developed heart problems. These include certain genes, called drug transporters, involved in pumping the drug out of heart cells. "We've found some preliminary markers that are promising," says Carleton.

Their goal is to develop a genetic test that can predict who is at high risk for heart failure. "I can see a day when the dose, or the type of drug, will be based on your genes rather than your body surface area," says Rassekh.

The network has collected DNA samples from more than 3,000 kids affected by ADRs and more than 25,000 who took the same drugs safely. Using this large and growing DNA bank, Hayden and Carleton hope to develop tests that can predict the safety of many different drugs for children, and help prevent the most common and severe ADRs.

The future: Customized care?

The network's research is already saving lives. In the case of codeine, network investigator Gideon Koren discovered that some nursing moms metabolize the drug in such a way that it can be life-threatening to their babies. The impact was immediate: The FDA in the United States and Health Canada issued warnings that breastfeeding moms taking codeine should watch their infants for shallow breathing, limpness, unusual sleepiness (sleeping more than four hours at a time), and other signs of morphine overdose. Regulators also required drug manufacturers to change the labelling of medicines containing codeine to highlight the potential risk.

Koren, director of the Motherisk program at Toronto's Hospital for Sick Children, found in a 2009 follow-up study that nearly 25 percent of breastfed babies became less alert or had abnormal breathing after their mothers took codeine. So, an ADR that was thought to be rare happens more frequently.

The network is now doing a study to test the benefits of a predictive genetic test for mothers that might help prevent codeine ADRs in breastfed infants. Three hundred women giving birth by Caesarean section at hospitals in Toronto and London, Ont., will take a simple DNA saliva test to see if they metabolize codeine very rapidly. Those identified as ultra-rapid metabolizers will be given another pain reliever, such as ibuprofen.

Another control group of 300 women will receive a standard dose of codeine medicine for pain relief, and both the moms and their babies will be closely monitored for ADR symptoms. If the study shows that personalizing pain relief treatment to match a woman's genetic makeup is safer for her and her baby, this could mean that the test would be offered to women giving birth in hospitals across the country.

Making drugs safer for kids matters to all families. More than 50 percent of kids take prescription drugs annually, many of them receiving multiple prescriptions a year. And we now know that some kids face much greater risks based on their genes. The CPNDS is working to lower that risk. "These are not just unfortunate side effects," says Carleton. "We need to treat disease without creating additional disability."

For Tent, a genetic test that could have predicted her son's risk of permanent hearing loss would have made a huge difference. "I would love to have had that choice. If I'd had the option of giving him another drug or a lower dose of cisplatin, I'd have gone for it," she says. Knowing that Stefan's case helped researchers at BC Children's Hospital find a way to prevent similar reactions in other children means a lot to her. "It's amazing. So many kids will benefit from this test, and their parents will have a choice."