 |
 |
|
| Archive : Summer
2006 |
WHEN A PATIENT'S GENES EXPRESS THEMSELVES, THEY MIGHT:
Suggest that a certain treatment is almost sure to work // Signal that heart transplant rejection is imminent // Advise against chemotherapy // Issue other messages we don’t yet understand.
Medicine Gets Personal [page 4]
 By Anita Slomksi
|
|
|
Even better than treating the expression of a defective gene would be replacing the gene with normal DNA. Since 1990, researchers have been trying to correct genetic defects by inserting chemically produced DNA into a vector—typically a virus stripped of its ability to replicate and cause illness—and injecting it into cells so that they will follow the inserted DNA’s instructions and behave like normal cells. Unfortunately, results have been mixed, even disastrous.
An 18-year-old died in 1999 after a severe immune response to the DNA-bearing virus intended to replace a broken gene that prevented his liver from making an essential enzyme. Since 2002, three “bubble boys” in France have developed leukemia after doctors replaced the faulty genes on their X chromosomes that had left them without immune systems. (As many as seven others have been successfully treated, however, and a similar trial cured several children in England suffering from the same affliction.) And recently, a gene-replacement trial in Germany significantly improved the ability of two men with another rare immune deficiency disorder, chronic granulomatous disease, to fight infections.
The FDA, worried about potential harm to patients, now restricts gene trials to small numbers of individuals and with very low initial doses of DNA. But those requirements have done little to slow research that continues to explore gene therapy as a treatment or cure for many diseases, including muscular dystrophy and Parkinson’s disease. In one experiment, a Phase 1 clinical trial involving 12 patients, William J. Marks Jr., associate professor of neurology at the University of California at San Francisco, and physicians at Rush University Medical Center in Chicago are injecting into the brain a viral vector containing the DNA that codes for a growth factor protein called neurturin. Marks hopes that the DNA’s genetic instructions will prompt brain cells to start making neurturin, keeping those cells alive and producing dopamine, the neurotransmitter involved in controlling movement and that is depleted by Parkinson’s disease.
Viral vectors packed with DNA may also change how drugs are delivered. Injected DNA could be targeted to the exact site of disease, avoiding toxic side effects that may result from taking a drug systemically. The biotech company GenVec, for example, has used a gene that, when injected into the heart of a patient with severe coronary artery disease, triggers the production of vascular endothelial growth factor, which generates blood-vessel growth in areas of the heart starved for oxygen. Another GenVec gene promotes a tumor necrosis protein that damages tumor blood vessels.
“You can kill a tumor with a locally produced protein that would be too toxic to give as a drug,” says GenVec president and CEO Paul Fischer. What’s more, because vector-delivered DNA isn’t incorporated into the cellular DNA, local protein production is temporary, on the order of months rather than years, says Fischer. And for cancer at least, clinical trials have shown that one injection is adequate to shrink tumors in combination with chemotherapy and radiation so they can be surgically removed, increasing the two-year survival rate from 10% to 30%.
Each new piece of information about genes and their expression reveals another possible pathway for taming disease at its most basic level. But progress won’t be as rapid as many people outside medicine would like to think. “The success of the Human Genome Project led many to expect an avalanche of approaches, tests and treatments that would revolutionize medicine,” says Bruce Korf, chair of the department of genetics at the University of Alabama at Birmingham. “In fact, though the progress is dramatic, it is gradual. Some findings have made a huge difference, like the discovery of a gene for breast cancer. But the complexity is enormous. The genetic revolution will likely be an evolution. It’s like watching the first airplane flight in the beginning of the twentieth century. It took more than 50 years before people were routinely flying across continents.”
 Dossier
1. “Pharmacogenomics: Harbinger for the Era of Personalized Medicine?” by Wolfgang Sadee, Molecular Interventions, 2005. Outlines how genetics will affect choice of drug therapy and the changes in drug research that must occur before personalized medicine reaches its full potential.
2. www.personalizedmedicinecoalition.org. Compilation of new reports on the latest genetic discoveries, tests and treatments, as well as in-depth articles on personalized medicine.
|
More
|
Back to top | Pages: 1 2 3 4
Photo by Lee Williams; Photo of Hand: Don Farrall/Getty
Images
|
|
|
|
