When Drugs Don’t Work

By Medial Discovery News

July 14, 2012



Without the liver, many important medications would simply pass through the human body and not produce any effect. The liver is able to metabolize and break down drugs or chemically alter them so that they become active.

But people with certain genetic variations either process drugs more quickly or lack the ability to metabolize specific drugs. Patients who are unaware they possess such a genetic trait could face potentially fatal complications if their lives depend on the very drug their livers can’t process.

This problem comes up in patients who get cardiac stents. Since the 1990s, hundreds of thousands, if not millions, of Americans have had stents put in. It is a metal mesh tube that is inserted into a blocked artery, especially in heart attack victims, to keep the artery open. A drawback is that within months, the artery can close back up as scar tissue grows. To solve this problem, a new stent came on the market in 2008 that slowly releases medication to prevent tissue growth. Yet the enormously popular stent carries a big risk: clot formation. The body tends to respond to the bare metal as a foreign object and cover it with platelets, increasing the risk of a fatal heart attack or stroke.

To prevent this, patients are given blood thinners, such as Plavix (clopidogrel), for at least a year.  Studies have shown the drug greatly decreases a person’s risks for developing clots. However, a rather large percentage of people carry a genetic variation that does not metabolize Plavix, which means the drug won’t work.

Forty to 50 percent of people with Asian ancestry, 30 percent with African ancestry, and 25 percent with European ancestry can carry this genetic variation. Doctors usually do not know until a patient with a stent begins forming blood clots, and genetic testing for the variation takes days. Now a Canadian company, Spartan Biosciences, has developed a bedside gene test capable of detecting this gene variant.

This gene encodes a liver enzyme belonging to a family of enzymes called P450 that is important in processing drugs. Of the eight known variants of this gene, seven encode inactive versions of the enzyme. The new machine can screen patients for these variants in about an hour.

Tests done at hospitals show personnel are capable of using the machine with little training and results are quick. Spartan Biosciences is waiting for regulatory approval of its machine in Europe and America and hopes to have it in hospitals soon. The company will give away the machine but charge about $200 per test.

The company is also exploring other applications for their technology, including determining drug resistance patterns of a bacterial superbug, methicillin-resistant Staphylococcus aureus (MRSA), and hereditary resistance to standard Hepatitis C treatments. This is likely only the beginning of bedside genetic testing. Ultimately, entire human genomes could be sequenced and analyzed next to the patient, helping doctors practice  personalized medicine.

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