Gene Therapy Experts Seek Safer Studies

From the WebMD Archives

March 8, 2000 (Bethesda, Md.) -- After a series of shock waves, including the first patient death from a gene therapy treatment last year, a federal review committee attempted to move on with its work of supervising these controversial experiments with a new emphasis on safety.

"There is a lot at stake here ... the people who are watching are the patients and families who are hoping in the long run that we develop new treatments," Lana Skirboll, PhD, told the Recombinant DNA Advisory Committee (RAC) at the beginning of a three-day meeting here Wednesday. Skirboll is director of the Office of Science Policy at the National Institutes of Health (NIH).

Last December, the RAC struggled to deal with the death of 18-year-old Jesse Gelsinger during a gene therapy study for an inherited liver disorder. Then in January, the FDA ended that study at the University of Pennsylvania amid charges the researchers withheld information about dangerous side effects linked to the procedure.

Last week, promising experiments about the possibility of using a gene to grow new blood vessels in patients with heart disease were halted, because the lead researcher apparently failed to report two patient deaths to the NIH.

In the wake of these irregularities, the FDA and the NIH, at the direction of President Clinton, announced new guidelines on Tuesday aimed at enhancing protections for patients in gene therapy studies. The effort, according to the release, comes in the wake of evidence that the "monitoring by study sponsors of several recent gene therapy trials has been less than adequate."

"The kind of event that happened with Jesse simply won't happen again. That doesn't mean there won't be deaths, but at least there won't be situation where people weren't aware of what was going on," W. French Anderson, MD, director of the gene therapy laboratories at the University of Southern California in Los Angeles tells WebMD. Anderson has been credited with performing the first gene treatment in 1990.

After a decade of rising expectations, but still no gene treatments on the market, Anderson says, "The growth spurt's about to begin." While he calls the Gelsinger episode painful, he says the changes it's bringing to the field are positive.


Specifically, FDA will now require researchers to submit their safety plans routinely to the agency, including information about who is actually monitoring the experiments. Anderson estimates that might add $80,000 to the cost of a single safety trial. In addition, the NIH and FDA are initiating a series of public symposia on critical patient safety issues in gene research. The first such discussion involving safer methods of replacing genes in the body is underway at this RAC meeting.

Typically, a virus, often an adenovirus similar to one that might cause a cold, is used to transport the gene treatment to an exact location in the body where it will hopefully crank out a normal protein. However, in Gelsinger's case, the virus itself may have triggered the reaction that led to his death.

One alternative now being considered by researchers is a "gutless" adenovirus from which most of the potentially toxic portions have been removed. The approach has been tested successfully in animals and may be first used in humans to replace a gene that prevents bleeding in hemophiliacs. If the gutless virus succeeds, it may eventually replace the earlier, more dangerous methods of delivering genes.

However, long-time critic of gene therapy Jeremy Rifkin, president of the Foundation on Economic Trends, isn't impressed by attempts to make the treatment safer. On Friday, he plans to ask the RAC for an "immediate moratorium" on gene experiments "except where the protocol can legitimately be considered a treatment of last resort for a life threatening illness."

"I don't think there's any serious concern on anybody's part that a moratorium is necessary or useful, but I think it's important that the issue be discussed," says Anderson.

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