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November 22, 2006
I Dream of Gene Therapy
by Laura Whitehorn
Timothy Spaulding, a clinical trial guinea pig for the HIV gene therapy known as VRX496, didn’t mind the needles or even the five hours he spent hooked up to a machine two summers ago at the University of Kentucky Hospital in Louisville. “It smells like garlic,” he recalls pleasantly of his periodic visits since then to have his own VRX496-charged blood pumped back into his arm.
For most of us, though, gene therapy is science fiction. And when VRX496 made the news earlier this month, people with HIV wondered what scientists were cooking up. Viral loads were down and CD4 counts were up in one VRX496 clinical trial—even though it was only being tested for safety—and it was time for some questions.
Among them: Won’t mucking around with genes turn our brown eyes blue? And what exactly would replace HIV’s familiar pill-popping routine if this experimental therapy is approved?
First, to be clear, this is not Jurassic Park. VRX496 is an artificial gene that is planted in the CD4 cells of HIV positive people so that they will churn out fake HIV viruses that aren’t able to reproduce. Presto change-o—so goes the theory—your viral load stops climbing, and you stop getting sick. But VRX496 messes with nothing in your basic genetic makeup (and dinosaurs are extinct).
As for the experience of gene therapy, researchers say the accounts of trial subjects like Spaulding, a retired government worker from Lexington, Kentucky, are pretty close to what people with HIV can expect if the method is one day OKed for general use.
It all starts with a one-time five-hour blood draw. Spaulding watched TV during his session, while tiny plastic tubes carried blood out of one arm through a gurgling “computer” and back into the other. Three months later, his CD4 cells had been re-engineered and returned to his doctor in the form of frozen blood. Spaulding visited four times for 15-minute infusions of the stuff. (Nurses attributed the garlicky smell to one of the chemicals mixed in at the lab. “I told the nurses I’d bring salad and pasta next time,” he says.)
The promise of gene therapy for people with HIV is that they may one day go months without having to think about treatment and that side effects will become a thing of the past.
But does it work?
The VRX496 trial veteran who got the best results in the trial that was reported on (we’ll call him Phase I Phil) was resistant to a range of meds and had a 50,000-plus viral load when the trial started and emerged with a viral load just under 2,000 and 300 to 400 CD4 cells. Two others out of a total of five subjects also responded to the therapy, while the last two got no benefit. Spaulding’s viral load fell from above 40,000 to around 10,000 during his (separate Phase II) VRX496 trial.
Donald Kohn, MD, of Children’s Hospital Los Angeles, a gene therapy researcher for 22 years, isn’t ready to give VRX496 full credit for the glowing reports, however. He calls the VRX496 approach “fairly heroic—a first,” but says the high CD4 counts reported may simply be owed to all the new CD4 cells being fed into subjects’ bodies.
VRX496 researcher Carl June, MD, counters that viral loads don’t fall when subjects get plain old CD4 infusions—only when VRX496 is added.
June says that the prognosis for HIV gene therapy is still inconclusive, but he allows himself to dream. “The whole landscape of HIV treatment could change in the next few years,” he says. Among other promising avenues is an experimental HIV gene therapy that alters CD4 cell receptors so that they actually block HIV. June is consulting on that project as well and reports that human trials are projected to start sometime next year.
Don’t look for FDA approval on any of these gene therapies next week, however, or even next year. This is a slow boat. It took 18 months and 13 separate FDA safety approvals just to get approval for June’s Phase I trial.
Meanwhile, the lives of at least two guinea pigs have changed already. Both Spaulding and Phil are still on HIV combos. But gene therapy has bought them time and kept them well enough to use new HIV meds should they need them. Says Phil, “Life itself is the difference. I have options now.”