The Why Files The Why Files --

Gene Therapy: The eyes have it!


Progress: why so slow?
We've seen a strong suggestion that gene therapy helps with one genetic blindness, and shows promise in many animal experiments. But gene therapy was first suggested in the 1970s. So the Why Files wondered: What's taken so long?

A shot in the dark
"In the beginning, the whole field did not know what the problem set was," says ophthalmologist Jean Bennett of the University of Pennsylvania. "Now we are pretty familiar with it: delivery, stability, immune response and gene regulation [making sure the gene product appears when it's wanted]." Bennett, who is developing gene therapy for blindness, says 142 known mutations cause retinal disease, and each may pose its own set of challenges. And that's just one tissue among many that can suffer from genetic disease.

Long, steady progress
Gene therapy was first proposed in 1972 (see #10 in the bibliography), says Pedro Lowenstein of UCLA, and while the public may be disappointed at the paucity of cures, "I think for the last 36 years, there has been steady progress. People did not know how to cut and paste genes, now we can, and put them into the viruses." Other basic advances included pinpointing the relationship between specific genes and diseases, and developing vectors (viral gene-carriers) that ferry genes to their destination while causing neither cancer nor massive immune reactions. And when all those questions are answered, Lowenstein adds, "You have to see if you can treat patients." Until then, he insists, "Gene therapy is not therapy."

Heavy hype?
"I think gene therapy was oversold, consciously by many investigators, to get attention, venture-capital funding, grant funding," says Andreas Beutler of Mt. Sinai School of Medicine in New York. "Some people hoped they could strike gold very quickly, but those who were serious in the field understood there were many hurdles," including the key area of vector development. Such hype accompanies many promising treatments, Beutler adds, including monoclonal antibodies -- identical biological molecules that have highly focused effects on the body. Ten years ago, after decades of research, monoclonal antibodies, like the breast-cancer drug herceptin, finally reached the market. The clinical use of a second highly touted advance, embryonic stem cells, is years or decades away.

Failure helps
The many setbacks in gene therapy have been a goldmine, says Brian Kaspar, of Nationwide Children's Hospital in Ohio. "There are certainly failures, because one cannot predict completely what will happen, but there have also been advances based on the fact that the field has gathered information to improve gene therapy." Information from a well-designed experiment that does not cure can still be help improve the animal models that are the foundation of gene-therapy research, but biology is complicated, and so is gene therapy, Kaspar says. "Unfortunately, the science takes time, and everyone wants things to work the first time," he says.

Get treated right in our gene-therapy bibliography.

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Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive

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