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PHILADELPHIA — A novel gene therapy that uses a genetic version of a Trojan horse has shown promise in fighting the AIDS virus, a coup in a field crippled by disappointments and setbacks.

The therapy is being tested at the University of Pennsylvania, where the 1999 death of 18-year-old Tucsonan Jesse Gelsinger still casts a pall.

His death, the first in a gene-therapy experiment, triggered a nationwide halt in human testing of such treatments amid revelations of ethical and regulatory lapses.

Seven years later, a team led by Penn's Carl June and Bruce Levine has achieved a gene-therapy tour de force: It has removed some infection-fighting "T cells" from five HIV patients, inserted a gene into the cells to stop the AIDS virus from reproducing, then multiplied the modified T cells and put them back in the patients.

The vehicle, or "vector," that the researchers used to deliver the protective gene to the cells was a genetically modified HIV virus — also a first.

The five patients, who were no longer responding to conventional HIV drugs, have had no serious side effects during two years of follow-up. Four showed signs that the therapy was working — very unusual in such a preliminary clinical trial.

"In a way, it's a redemption," Levine said of the results, published Monday in the Proceedings of the National Academy of Sciences.

Mark A. Kay, a Stanford University researcher and past president of the American Society of Gene Therapy, said: "The whole technology it took to get this done was cumulatively very strong. It wasn't clear to me that this was going to work. But I think this is an important step forward. I'm impressed."

So is "Subject 2," a Philadelphia resident who has had the most dramatic, sustained effects. His HIV viral load fell from 54,100 three years ago to 1,930 last January. His supply of T cells, which had been so ravaged by HIV that he was on the edge of an AIDS diagnosis, increased slightly. The modified T cells were detectable in his bloodstream for two years. And his immune system grew stronger.

"When I tested positive in 1989, I really didn't expect to live this long, so I'm very grateful," said the muscular, 44-year-old public administrator. "Now I don't expect to be gone anytime soon."

On its own, a virus can't reproduce; it must infect a cell and hijack the host's machinery to make copies. Some viruses, including the human immunodeficiency virus, do this by splicing their own genes into the cell's DNA.

By using these invaders to insert DNA that is helpful to the cell rather than harmful gene therapy can theoretically fix the root causes of many diseases. But the obstacles to this simple-sounding strategy have proved to be enormous.

For one thing, even when researchers deactivate the disease-causing genes in a viral vector, the immune system may spot the invaders and attack. That, investigators concluded, is what killed Gelsing-er: The adenovirus (cold virus) that was supposed to deliver therapy for his rare metabolic disorder sent his immune system into deadly overdrive.

The subsequent suspension of all U.S. gene-therapy trials "cost us two years of progress," recalled June, a professor of pathology and laboratory medicine.

Another obstacle is that the characteristic of viruses that makes them useful as vectors — their constant swapping and shuffling of DNA — also makes them hard to control. In theory, viral vectors can recombine with viruses already in the patient, or insert their genetic payload into the host's DNA in a way that triggers cancer.

That theory became reality in France. Three of 10 children who underwent gene therapy and were cured of severe combined immune deficiency disease — the so-called "Bubble Boy" disease — later developed leukemia. One died in 2004.

Designing a clinical trial took almost three more years because Penn, the National Institutes of Health and the Food and Drug Administration have learned to err on the side of rigorous caution. At Penn alone, a dozen oversight boards had to approve the study.

The researchers were allowed to give five patients a single conservative dose. They had to wait three months between each patient and develop special tests to monitor for unintended genetic combinations. Each volunteer signed a 16-page consent form.

"Did we feel confident it would work? No," June said. "We felt we had the right ethical setting and it was worth a gamble. If I had HIV, I would try it."