Top Eye Expert Optimistic About Gene Therapy Cure for Blindness

May 2, 2007— -- A top eye scientist at the National Institutes of Health has called a new procedure that uses gene therapy to correct a condition that leads to blindness "an exciting development" that could pave the way for additional gene treatments for blindness and other conditions.

But some ophthalmology experts remain skeptical. And with months remaining before the procedure can be declared a success or a failure, the weeks in between will likely be filled with debate, speculation and, possibly, high hopes.

Surgeons at London's Moorfields Eye Hospital, led by Robin Ali, a professor, performed the first-of-its-kind procedure Tuesday on Robert Johnson of the United Kingdom, the BBC reported. Johnson was born with Leber's congenital amaurosis, a gene-linked sight disorder that gets worse with age.

Dr. Paul Sieving, director of the National Eye Institute in Bethesda, Md., says the procedure culminates about 15 years of research and animal experiments. And he is optimistic that the treatment will work.

"A number of years ago they did this with dogs, and five years later, they are still seeing fine," Sieving says. "If it could help people with that condition, it would be wonderful.

"The accumulated hard work of scientists for decades and the genetic revolution of the past 15 years are beginning to pay off."

But Dr. Richard Bensinger, an eye surgeon at Swedish Medical Center in Seattle, says it is too soon to celebrate, as past gene therapy experiments have shown little progress.

"This logic so far has failed, and no gene transfer experiment has worked," he says.

An Infectious Treatment

Whether it succeeds or not, few can argue that the idea behind the procedure is an elegant one.

The reason for Johnson's blindness is a faulty gene in the cells of his retina. This nerve-filled spot in the back of the eye acts a bit like the film in a camera, capturing light and sending the picture it receives to the brain.

Doctors believed they may be able to restore Johnson's sight if they can replace the faulty genes in the cells of his retina with properly working copies. They accomplished this feat using a harmless virus to deliver new, nondefective genes directly into the center of retina cells.

Using a needle, doctors injected a dose of the virus straight into the eyeball. The virus "infects" the cells of the retina, replacing the defective genes in these cells with the properly functioning copies.

So far, the strategy has shown some success -- in animals, at least. In 2001, a team of researchers from Cornell, the University of Pennsylvania and the University of Florida-Gainesville performed the first such procedures on a dog afflicted with a condition similar to Johnson's.

The results, published in the May 2001 issue of the journal Nature Genetics, revealed dramatic improvement in the dog's vision.

"The dog, within a couple of months, was able to play Frisbee," Sieving says. "It was really remarkable."

Sieving says the condition is a natural candidate when it comes to gene therapy, as the disorder is caused by a single, known gene.

"This has been the disease of choice within the genetic eye diseases," he says. "This is a designer condition to see gene therapy in the eye."

He says, however, that results would take a while to see, since the virus takes time to fully insert the replacement genes into the cells of the retina. "That process takes something on the order of several weeks to several months."

But he says that if the procedure turns out to be effective, is should be performed in patients "as soon as you can identify the people."

"It's a very exciting time for the science of genetic diseases," says Sieving. "The issue is to get the science converted to practice so it can benefit you, my children, everybody."

He adds that what is happening now will also help determine the safety of putting a gene and viral vector into the eye.

"I am presuming that this is safe and usable for other genes," he said. "This opens the door to treatment of a whole repertoire of eye diseases."

Some Experts Skeptical

Several ophthalmology experts refused to comment on the procedure, some saying it was too early to tell whether the approach would show success in a human patient.

And Bensinger says the procedure comes attached with considerations that could make it difficult to achieve the desired outcome.

"The difficulty in gene therapy is the lack of ability to insert the normal gene into the existing DNA of the recipient," Bensinger says, adding that the treatment normally causes the death of cells in the retina.

"The retinal cells do not reproduce after infancy, which makes gene transfer more difficult, as a virus-infected cell is likely to die -- not the desired result since it cannot replace itself," he says. "The bottom line is that more details are needed to analyze this. It is probably a 'first,' but that does not mean it is likely to succeed."

There is also the question of safety. While some patients have benefited from gene therapy, the 1999 death of an 18-year-old patient receiving gene therapy for a metabolic disorder caused many to reconsider the approach.

Johnson's procedure, however, differs from some other gene-therapy procedures performed in the past, as it deals with a very small area of the body -- namely, a spot of nerves on the back of the eye. This may make it safer than some gene therapy procedures that affect the entire body.

A Bellwether Procedure?

Despite the uncertainties, Sieving says the treatment could have implications for a number of other genetic diseases if successful.

And many of these treatments could start in the eye. According to the National Eye Institute, nearly 500 genes that contribute to inherited eye diseases have been identified over the past 15 years. These genes are associated with conditions ranging from glaucoma and cataracts to retinal degeneration.

Sieving believes that this most recent procedure will just be the first of several that will come out over the next few years. He says a comparable trial for retinal treatment is slated soon in the United States at the University of Pennsylvania, and he adds that gene therapy solutions for other conditions may be on the way.

"Whatever transpires in Moorfields will likely be replicated and vetted elsewhere," he says. "I think that we should celebrate a success story here. We, of course, have to make sure that this is a success, but even to get here, to this point, is a remarkable story."