Genetic diagnosis is further ahead than genetic therapy. A genetic test to predict whether a patient with hepatitis C will eventually suffer from cirrhosis of the liver, and one to help determine which patients should receive aggressive early treatment for prostate cancer, have been developed.

Genetic diagnosis is an essential aspect of pharmacogenomics — drugs tailored to an individual’s genomic quirks. But just as we’ve all learned to pronounce pharmacogenomics, along comes pharmaco-metabonomics. Don’t be surprised to see pharmaco-proteomics and pharmaco-glycomics in the news one of these days. But it’s all in a good cause: The drive towards personalized medicine.

Like most drives, this one is not without resistance. In 2005 the FDA approved a pharmacogenomic test from Roche Diagnostics that allows less specialized labs to test for genetic defects that directly affect a patient’s ability to metabolize a substantial number of drugs, including nearly all drugs whose mis-metabolization causes serious side effects or death. A department chair at the Mayo Clinic thinks the use of the test, which can cost up to US$1,360 (though it would usually be much less) and is not reimbursed by many insurers, is a no-brainer given its benefits, and he uses it “very regularly.”

But an assistant professor at the Uniformed Services University of the Health Sciences would apparently prefer to rely on an “alert” doctor picking up clues as to the patient’s likely ability to tolerate and benefit from a potentially lethal drug the old-fashioned way — from the patient interview, patient demographics, and medical history.

In an age of patients well informed by articles such as this one taking more responsibility for their healthcare, which doctor, and which institution, is the patient in need of serious medication likely to pick?

Experimental Gene Therapy for Muscular Dystrophy

Source article

In March this year, human trials began of an experimental gene therapy for Duchenne muscular dystrophy, a rare, inherited, degenerative muscle disorder that afflicts 30,000 in the US, mainly boys. The trial involves the injection of dystrophin genes into the muscle of one of the patient’s arms, and a sham injection into the other. Muscle cells from each arm will then be examined for evidence of dystrophin production, and muscle strength will be assessed.

Gene therapy has had a slow start, and the present trial is a cautious step toward a cure for Duchenne’s. If it proves safe and prompts the persistent production of dystrophin in muscle cells, researchers will move ahead with a more ambitious study — injecting the genes into the bloodstream.

Gene for FOP Identified

Source article

University of Pennsylvania researchers have discovered the genetic mutation that causes the disease fibrodysplasia ossificans progressiva (FOP), a ghastly condition that turns its victims’ muscles, tendons, and ligaments into bone. Any attempt to surgically remove the extra bone triggers explosive new growth.

It turns out that FOP is caused by the mutation of a single DNA letter out of six billion. The mutated gene prompts a bone-making protein to change a single one of the 509 amino acids that normally enable it do its job.

If FOP can be arrested or prevented, it might also be possible to stop the debilitating bone formations that can occur after hip replacement surgery, head trauma, and spinal-cord injuries in people who don’t have FOP.

Genetic Test for Hepatitis C

Source article

Celera Genomics has developed a genetic test to predict the likelihood of a patient with hepatitis C eventually suffering cirrhosis of the liver. The test assesses variations in seven genes.

Marker for Prostate

Source article

The recent discovery, by Iceland’s DeCode Genetics, of a variant gene associated with prostate cancer may lead to a diagnostic test to determine candidates for aggressive treatment.

The gene may also help explain why African-Americans, in whom the variant is more common, have a greater incidence of the disease. William B. Isaacs, a prostate cancer expert at Johns Hopkins University, told the New York Times that the new finding was “very exciting” and added that until now “there haven’t really been any clear-cut examples of genes identified by one group and reproduced across multiple study populations.”

Pharmaco-Metabonomics

Source article

Scientists from drug company Pfizer and London’s Imperial College are developing a “pharmaco-metabonomic” method to predict how individual patients will respond to medicines. The method uses a combination of advanced chemical analysis of the body’s metabolism and mathematical modeling to predict responses to drugs. It may also help to diagnose diseases and predict an individual’s future illnesses.

Physician Resistance

Source article

Editor’s note: The following is a small selection from a long but highly informative article about pharmacogenetic tests, written by Lisa Barrett Mann in the Washington Post — see the source article link for the complete article. We’ve covered genetic tests in previous issues, and have limited this selection to highlight the problem of physician resistance to change.

… David Mrazek, chairman of psychiatry and psychology at the Mayo Clinic, says he does such [pharmacogenetic] testing “very regularly,” especially with children (who are particularly vulnerable to drug side effects) and patients with a personal or family history of adverse drug reactions. Many other doctors in his field are unfamiliar with the tests or don’t use them.

Mrazek is convinced of the value of genetic testing for enzyme problems. “Before I would put any child” on a drug metabolized by the 2D6 enzyme, he says, “I would want to know that they have at least one good copy of the 2D6 gene. . . . I’ve been very surprised by some very senior psychiatrists saying, ‘I don’t need this; I’ve been prescribing Prozac for years.’ Young clinicians are very quick to say, ‘Gee, here’s a tool that can potentially prevent a tragic event.’ ”

But an assistant professor at the Uniformed Services University of the Health Sciences regards the testing as an unnecessary expense for most patients. An alert doctor, she says, should be able to recognize drug metabolism problems clinically. For example, she can ask patients, “Have you ever had any problems taking Robitussin? Does it make you queasy or jittery or sleepy?” Since Robitussin is metabolized by 2D6, a “yes” could be a red flag.

She also notes that many factors besides DNA can affect liver enzyme production, including age, weight, diet, other drugs and smoking. Brain receptors may also affect how the body reacts to different drugs. Then there’s the question of cost. Genelex will test for a problem on one gene for $250; a battery of tests for four genes costs $800.