Gene therapy benefit said to outweigh risk

By STEVE MITCHELL, UPI Medical Correspondent  |  Oct. 10, 2002 at 7:04 PM
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WASHINGTON, Oct. 10 (UPI) -- The benefits of gene therapy far outweigh its risks and such procedures hold the greatest hope for treating currently incurable diseases, experts told United Press International.

This assessment was given despite the U.S. Food and Drug Administration's decision to hold an emergency meeting Thursday to examine gene therapy safety issues following the report last week that a person had developed cancer from the treatment.

In addition, a clinical trial of gene therapy in France being conducted at the Hôpital Necker Enfants Malade in Paris was halted after a patient developed leukemia apparently due to the vector that was used to deliver the gene into the body. The trial was using gene therapy to treat patients with X-linked severe combined immune deficiency, a disease that is fatal within the first few years of life if not treated.

The FDA acted last week to halt all similar trials in the United States -- there were thought to be only three.

Yet these events have no bearing on other gene therapy trials, experts said.

"People tend to group gene therapy together ... but in fact the only similarity is that you're putting a gene in," said Mike Kaplitt, a neurosurgeon at Weill Cornell Medical College in New York City who will soon begin the first ever gene therapy trial for treating Parkinson's disease. "That's like saying every drug therapy is the same because you're putting a drug in."

Kaplitt told UPI the problem in the French trial appears to be due to the vector -- usually a virus -- that was used. But he noted different gene therapies use different vectors and not all of them carry this risk.

The French trial used a retrovirus that has long been considered to be safe, said French Anderson, director of gene therapy laboratories at the University of Southern California in Los Angeles and the first to use the vector in humans in the early 1990s. Anderson said the vector has been used for 12 years and in more than 3,000 patients before a side effect was seen. It was known the vector had the potential to insert into chromosomes and cause cancer and patients in the French trial were informed of this risk, but it never had occurred until last week, he said.

Because it was a known risk, "it's not going to have that much of an impact on the field," Anderson said. Referring to Jesse Gelsinger, who died in 1999 after being treated with gene therapy for a rare metabolic disorder, he said "that was totally unexpected and unexplained and that did have an impact on the field." The vector used in this case was different from that used in the French trial.

The Gelsinger incident resulted in regulatory agencies taking a closer look at gene therapy trials and instituting new safety measures, Anderson said. "The public should have a certain amount of confidence that regulatory agencies around the world are so alert to gene therapy that when one patient in Europe has a problem the whole world knows it within days. The time to get frightened is when you don't know what is happening, when things are kept secret," he said.

"In the midst of all this, the public shouldn't lose sight of the potential of these therapies," said Savio Woo, past-president of the American Society of Gene Therapy and director of the gene therapy institute at Mount Sinai University in New York.

"This adverse event needs to be put into context," Woo said. "These type of events (in gene therapy trials) make the front page but out of the thousands of patients who have undergone gene therapy ... the frequency has been really low, certainly no higher than new drugs under development," he said.

"That's not to say this event is not bad," he added. The scientific community "wants to take this on, find out how it occurred and how to prevent it in the future" because the treatment is "nothing short of spectacular" for patients with SCID, Woo said. He added that 11 of the patients, who would not even survive without treatment, have been given this therapy and 10 are cured and now living normal lives. "If that's not miraculous medicine, I don't know what is," he said.

Anderson agreed, saying, "Gene therapy is the greatest hope people have for what is presently incurable diseases."

Kaplitt said the vector he will be using in the Parkinson's trial is largely deemed to be one of the safest. It is called adeno-associated virus, or AAV, and it "has never been associated with any human disease whereas some of the other vectors have been," Kaplitt said.

Anderson agreed AAV appears to be safe but he noted that could change. "AAV is thought to be the safest viral vector and that will be the case until they produce a serious adverse event," he said. "It's only a matter of time before something pops up with AAV," he said, noting that it took more than a decade before a side effect was seen with the retrovirus vector used in the French trial.

Woo said the risk of such side effects must be taken in the context that gene therapy has enormous potential to cure disease. "There won't be any new medical therapies forever in the future if the public expects a new therapy to be completely safe the first time," he said.

Anderson also voiced his support for continuing gene therapy. "Everybody from Paul Gelsinger (Jesse's father) on down have made clear that if these cases were to hamper the progress of gene therapy that would be the biggest tragedy that could happen," he said.

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