Association for Better Child Care, Development & Education
'Dwight's Computers for kids'
The unprecedented feat may give hope to the nearly 10,000 Americans born with the same disease - and hundreds and thousands of others with closely related forms of blindness.
The work, led by researchers a the University Pennsylvania, marks the first time that congenital blindness has been reversed in an animal larger than a mouse. It suggests that someday, a single injection into the eye may restore vision in children born with a genetic disorder called Leber congenital amaurosis, one of several incurable forms of blindness collectively known as retinitis pigmentosa..
Doctors said they suspect 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 he eye. If ongoing studies in dogs go well, the researchers said , the first human studies could begin in 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 the University Pennsylvania's Scheie Eye Institute who was involved in the new study. "But that said, its hard no not to very excited about this, because its a very dramatic result. I mean, basically these dogs were blind and now they are not blind anymore."
Children with Leber congenital amaurosis have little or no vision at birth, and what little they may have is lost over time. It occurs when 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 haven normal vision. The condition affects children who inherit a defective copy 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 percent of Leber congenital amaurosis cases. Mutations in any of a dozen or so other genes also cause the disease, and mutations scores of other genes cause other forms of retinitis pimentosa.
Jean Bennet, Maguire's wife and coworker, led the new study, in which thousands of viruses were injected directly in the eyes of three blind Briard puppies. 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' retinal cells.
The dog's 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 a cluttered, 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 is difficult to measure visual acuity in dogs. But, by all measures, they are seeing very well nine months after they are treated, with no ill effects.
"We are bursting at the seams,' said Betsy Brint of Highland Park, Ill., whose 4 -year-old son, Alan, was born with Leber congenital amaurosis.
"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 created the Foundation for Tetinal Research with her husband, David.
Now, she said, everything is changing.
The new experiments, which included researchers at the Cornell University, are reported today in the May issue of the journal Nature Genetics.
But many questions need to be answered, experts said, before doctors can justify human studies -- especially given the ethical considerations of conducting experiments on young children.
If the technique proves safe and effective, Bennett said, it may work for other kinds of retinitis pigmentosa using viruses stuffed with the appropiate genes.
