Gene therapy has success restoring vision

A long-sought holy grail of medicine, gene therapy seems to be reversing a form of childhood blindness, and other genome-based treatments might not be far behind, the director of the National Eye Institute told an Augusta conference Friday.


Dr. Paul A. Sieving, who also does research on the genetics of eye diseases, spoke at the second annual retreat of the Vision Discovery Institute of the Medical College of Georgia, one of several discovery institutes at the school that join clinical researchers and basic scientists in the hopes of creating breakthroughs. It is something the national institute encourages, Sieving said.

"It really has to be an exchange, a community of people working on it," he said. "Hence, the really critical importance of the Vision Discovery Institute."

With more than 600 genes now identified that have been linked to eye diseases, vision researchers are poised to take full advantage of the wealth of genetic research, Sieving said.

"This is a gold mine for discovery, a gold mine for work," he said.

One of the first payoffs with gene therapy involves a relatively rare cause of blindness known as Leber congenital amaurosis. Patients with a certain form of that disease have a mutated copy of a gene called RPE65 that codes for an enzyme used to convert vitamin A to give the eye light sensitivity.

"You restore the gene, you restore the enzyme function and everything starts to run again," Sieving said.

Gene therapy to add a working copy of RPE65 in three young adults with the mutation appears to have restored some vision within weeks, and it was still functioning a year later, according to reports in The New England Journal of Medicine.

"This really has caught the attention of the entire gene therapy community for all disease in the country," Sieving said. "Next week, when (National Institutes of Health Director) Francis Collins testifies to Congress, he's going to tell Congress about this. The vision community is on the map because we have great systems and great science."

"That probably is going to be the first series of genetic therapy breakthroughs," said Dr. Julian Nussbaum, the chairman of MCG's Department of Ophthalmology and co-director of the discovery institute. "So you can see one gene, one protein, one treatment. You replace the protein by replacing the gene."

As the wealth of genetic information grows and genome sequencing becomes cheaper, with $1,000 individual genomes coming soon, it will transform medicine, Sieving said.

"This is now going to reach right into our eye clinics because we are going to think about disease differently," he said. "It is this kind of analysis that is going to cause us to rename disease, rethink how disease works, and ultimately will lead us to treating patients in new ways."

"Instead of treating the disease in general, (medicine) is moving towards treating the disease specific to your genetic profile," Nussbaum said.

When she came to MCG from the national institute 18 years ago, clinicians and scientists didn't mix much, said Dr. Sylvia Smith, a basic science co-director of the discovery institute.

"There wasn't any way for us to work together," she said. Now, eight joint projects are under way.

"It is very exciting," Smith said.