Gene Therapy Deals Blow Against Rare Blindness

Gene therapy to counteract retinal degeneration from a rare inherited sight disorder improved vision in all patients in which it was tested -- including one child who recovered near normal light sensitivity.

While the 8-year-old boy was the clearest success story, all the children with a condition known as Leber's congenital amaurosis treated in the study regained sufficient vision to walk unaided, Dr. Jean Bennett of the University of Pennsylvania in Philadelphia and colleagues reported at the American Academy of Ophthalmology on Saturday.

Younger patients appeared to respond best to the treatment, which involves injecting the eye with genetic material "piggybacked" on a virus, the researchers wrote in a paper released in the medical journal Lancet.

The trial provides hope for one of the most severe forms of inherited retinal degeneration, a disorder that currently has no treatment.

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But co-author Dr. Katherine High of Children's Hospital of Philadelphia cautioned against considering this treatment a cure at this point. "We don't know how long it will last," she said, though noting that the effect has lasted at least 10 years in animals.

Children born with a mutation in one of 13 genes that cause Leber's congenital amaurosis typically have severe vision deficits from birth that progress to total blindness by age 30 to 50.

Though the research on the treatment is still in its early phases and the results thus far have been based on only a few treated patients, the findings hold great promise, according to a commentary accompanying the Lancet paper.

Not only were the treatment effects sustained after only a single injection, but the same strategy may be effective in slowing or stopping retinal degeneration from other genetic causes, such as retinitis pigmentosa, wrote Frans Cremers and Rob Collin, both of Radboud University Nijmegen Medical Centre in Nijmegen, the Netherlands.

"As novel therapeutic strategies are being developed for each of the separate genetic defects, ascertaining and genotyping the corresponding patients will be the real challenge in the coming decade," they said, noting that even in the industrialized world less than 10 percent of patients know the genetic cause of their inherited blindness.

Gene therapy has already been applied successfully in animal models for eight genetic causes of blindness, including one that has been shown to be the cause of about 6 percent of Leber's congenital amaurosis cases.

Bennett's group looked at 12 patients age 8 to 44 with this particular genetic disorder. The researchers injected the worst eye of each patient with a shot that contained a virus designed to carry DNA into the cells of the retina -- the patch of sensitive tissue on the back wall of the eyeball that contains the nerves that send the impulses to the brain that are interpreted as images.

Over the next two weeks, all the patients reported improved vision in their injected eye in dimly lit settings. None had serious adverse events from the procedure.

Age wasn't a significant factor in how well the subjects responded to the treatment, though improvements in vision did seem to be tied to the amount of remaining retina that was still salvageable. Since the disease progressively destroys viable photoreceptors -- the cells in the retina that detect light -- the researchers said it may not have been a surprise that patients age 19 and younger had larger visual field recoveries than older patients.

White light sensitivity improved substantially for five of seven patients treated after the testing equipment became available, with benefits only in the treated eyes. The youngest patients enjoyed the greatest gains in sensitivity, the researchers noted.

Another objective measure of vision improvement -- dilation of the pupil -- improved in the injected eye of all 11 patients tested, whereas the untreated eye showed minimal constriction when exposed to light. The most notable improvement in pupillary-light-response sensitivity was in the youngest patient. The 8-year-old recovered nearly the same light sensitivity seen in a group of control patients without vision problems.

The injected eyes of the patients also seemed to possess improved ability to see in dim light settings, and the treated eyes also appeared to be able to fixate on objects better -- benefits that translated into four children able to navigate an obstacle course on their own after treatment with fewer errors and greater speed. Six patients overall were reclassified as no longer legally blind after treatment.

"The visual recovery noted in the children confirms the hypothesis that efficacy will be improved if treatment is applied before retinal degeneration has progressed," Bennett's group concluded.

In the long-term, the researchers hope to be able to administer genetic therapy as soon as a child is diagnosed with this condtion and thus rescue as much of the retina as possible, High said.