Gene Therapy Restores Sight in Dogs Born Blind

Dogs born blind are seeing the world for the first time after scientists injected new genes into their eyes. The unprecedented feat has electrified the families of the nearly 10,000 Americans born with the same disease--and hundreds of thousands of others with closely related forms of blindness.

The work, led by researchers at the University of Pennsylvania, marks the first time that congenital blindness has been reversed in an animal larger than a mouse. It suggests that a single injection into the eye may someday restore vision in children born with the genetic disorder--called Leber congenital amaurosis--one of several incurable forms of blindness collectively known as retinitis pigmentosa.

Doctors said they suspect that similar gene therapy treatments could prove curative for many of the 150,000 Americans suffering from that broad family of diseases, all of which involve a deterioration of the light-detecting retina in the back of the eye. If ongoing studies in dogs go well, the researchers said, the first human studies could begin in the next three to four years.

“We have to be careful not to fill people with false expectations or false hopes,” said Albert Maguire, an ophthalmologist at Penn’s Scheie Eye Institute who was involved in the new study. “But that said, it’s hard not to get very excited about this because it’s a very dramatic result. I mean, basically these dogs were blind and now they are not blind anymore.”

Children with LCA have little or no vision at birth, and what little may be there is lost over time. It occurs when there is a defect in any of several genes that help convert light into electrical signals in the eye. Parents carrying the defect on one copy of the gene have normal vision. The condition affects children who inherit two defective copies--one from each parent.

The new work was done on Briard dogs, which in the course of long-term breeding by humans have acquired a blinding genetic mutation in the so-called rpe65 gene--identical to the one that causes about 20% of LCA cases. Mutations in any of a dozen or so other genes also cause LCA, and mutations in scores of other genes cause other forms of retinitis pigmentosa.

Jean Bennett, Maguire’s wife and co-worker at the Scheie Institute’s F.M. Kirby research center, led the new study, in which thousands of viruses were injected directly into the eyes of three blind Briards. The viruses had been genetically engineered by scientists at the University of Florida to contain healthy versions of the rpe65 gene, which the viruses then delivered to the dogs’ ailing retinal cells.

The dogs’ left eyes got injections into one part of the eye--an area distant from the retina--with no effect. But the right eyes got injections directly behind the retina, very close to the so-called retinal pigment epithelial cells where the rpe gene does its job. Before long, all three dogs had vision in their right eyes.

A video shows the dogs navigating around a cluttered room, only bumping into objects when they are on the animals’ left side. Electrical measurements of the retina, resembling an EKG for the heart, appear normal. And pupil responses prove that the neural connections between the eye and the brain are working--evidence of real visual perception.

“It’s very exciting,” said Michael Redmond, a senior investigator at the National Eye Institute who has done seminal work on the rpe gene. “It’s just beautiful work.”

Previous studies on rats and mice with LCA had achieved temporary restoration of vision with a highly toxic nutritional additive, and longer lasting but only partial restoration with gene therapy. It’s difficult to measure visual acuity in dogs. But by all measures they are still seeing very well nine months after they were treated, with no ill effects.

“We are bursting at the seams,” said Betsy Brint of Highland Park, Ill., whose son Alan was born with LCA four years ago. “When Alan was diagnosed the doctors all said there’s nothing you could do and no cures and very little research going on,” said Brint, who with husband David created the Foundation for Retinal Research. Now, she said, everything is changing.