Gene therapy disappoints so far, U.S. experts say

RTw 25.09.97 03:40


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By Maggie Fox, Health and Science Correspondent
WASHINGTON, Sept 24 (Reuter) - Efforts at using gene therapy to treat sick people have been disappointing so far but are worth pursuing, experts said on Wednesday.

Despite newspaper headlines, millions of dollars poured into research and a lot of raised hopes, not a single person has been cured by giving them new, healthy genes, they told a conference.
"The long and short of it is that we have not achieved gene therapy," said Theodore Friedmann, director of the human gene therapy program at the University of California in San Diego.
"It's clear that most therapies for genetic diseases are ineffective," Friedmann told a seminar sponsored by the American Association for the Advancement of Science.
Nonetheless, Friedmann and other experts said they firmly believed gene therapy would happen. "We should have an enlightened public debate while the issue is still remote," he said. "It's fiction now, but it won't be for long."
He said polls showed strong support for using gene therapy to treat disease, and even for gene enhancement.
But while transgenic animals containing human and other genes had been created and even bred, work on humans was much slower, and rightly so.
"Humans are not mice. One cannot breed humans like mice. With mice one can just put mistakes away -- with humans, one cannot," Friedmann said.
Malcolm Brenner, director of the gene therapy program at St Jude's Children's Research Hospital in Memphis, Tennessee, said it was not surprising that the 400 clinical research protocols under way into gene therapy had produced little.
Gene therapy was difficult, he said. First the faulty gene or genes had to be identified. Then the new gene had to be targeted to the nucleus of the right cell, and it would have to hook up with the cell's DNA in just the right place.
The perfect vector, or vehicle for carrying the gene, had not been found. Viruses were hard to control, while liposomes -- essentially cases made of fats -- did not last long.
Then the gene's product -- all genes "code" for production of a protein -- would have to be regulated.
"I don't think any of the vectors we have now are anywhere close to achieving this," Brenner said.
So far gene therapy, even when it did work, affected only a tiny proportion of the cells in the human body, he added.
Yet people wanted to believe in gene therapy.
Cystic fibrosis was an example of a gene therapy experiment that was "greeted with enormous -- I think absurd -- hype," Brenner said.
Doctors hoped cystic fibrosis would be an easy first target. It is caused by one gene and many of its effects are seen in the lungs, which are easy to reach with inhaled drugs or drips.
One effect of cystic fibrosis is the buildup of mucus and frequent lung infections. Researchers thought adenoviruses, a family that included cold and flu viruses, was appropriate to carry genes to the lungs.
But instead, Brenner said, the adenoviruses caused inflammation and in some cases worsened the condition.
Nevertheless, Brenner said, scientists had to keep trying.
"It hasn't cured anybody yet but it has helped some patients," he said. For example, his team inserted a gene for interleukin-2 -- an immune system product that acts against tumors -- into children with the childhood cancer neuroblastoma.
The tumors were definitely affected. "I still believe it is very much worth exploring the area," Brenner said. REUTER


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