Washington

How do you resurrect a therapy stalled by a crippling combination of regulatory, financial and scientific hurdles? At a meeting in Arlington, Virginia, last week, gene therapists spelled out the problems in unflinching detail, but concluded that gene therapy can be revived — if its practitioners are willing to make changes.

“This course of events has been experienced by other new therapeutics,” said Katherine High, president of the American Society of Gene Therapy, which convened the meeting on 7–8 April. She cited the example of monoclonal antibodies, which went through a cycle of hype, disappointment and eventual medical and commercial success.

Concerns about safety have made patients reluctant to participate in clinical trials, and regulatory requirements have made trials expensive. The National Institutes of Health (NIH) does not have the resources to fund many clinical trials, and big pharmaceutical companies are not interested in diseases that afflict relatively few patients.

So how can gene therapy continue? Suggestions from the meeting included modifying the molecules used to deliver the genes, developing better animal models, and performing more rigorous safety evaluations before beginning trials in people.

But Daniel Salomon, a transplant surgeon at The Scripps Research Institute in La Jolla, California, who headed up the US Food and Drug Administration's advisory panel on gene therapy until 2003, thinks the field needs a more profound change of approach.

He argues that trials ran into safety problems because gene therapists did not take the body's immune response seriously enough. “Everything you do that damages healthy tissue, you're going to pay a price for.”

Others agree. “Some of us do molecular biology because we don't have to learn immunology,” says Savio Woo, a gene therapist at the Mount Sinai School of Medicine in New York.

Salomon is hopeful nevertheless. Gene therapists must understand and plan for the immune system's response to experimental treatments, he advises. This could entail using immunosuppressive drugs. “Gene therapy is going to happen,” he says. “A dose of reality is all I'm talking about.”