Blind World Magazine

Researchers hatch gene-transfer therapy to make blind chickens see.




Canoe Online, Canada.
Monday, May 22, 2006.




TORONTO (CP) - It's one of those questions that has baffled humans for millennia: What came first, the chicken or the egg? For scientists seeking a way to give sight to genetically blind chickens, it was definitely the egg.


Researchers from the University of Florida injected healthy genes through the eggshells of chickens with an inherited disorder that causes them to be born blind. When the treated chicks hatched, not only could they see, but their vision was "amazing," said neuroscientist Sue Semple-Rowland, the principal researcher.


More importantly, the gene-transfer raises high hopes for developing a treatment to restore sight in children with a similar condition, called Leber congenital amaurosis Type 1, or LCA1.


"I firmly believe this will work," Semple-Rowland said from Gainesville, Fla. "We're really, really close to making it possible to treat kids with various forms of LCA with gene therapy and have them have a relatively normal life in terms of vision."


While there is much work still to be done, she predicted a treatment for humans could come within just a few years.


The breakthrough with the chickens took 20 years of painstaking work by Semple-Rowland and her colleagues to determine what caused the birds' blindness, to isolate the defective gene and then to figure out how to fix it.


Her lab modified a virus to carry a normal copy of the gene that is defective in the chickens, a type of Rhode Island Red. After boring tiny holes in the shells of fertilized eggs, they injected a small quantity of the virus into the neural tubes of two-day-old embryos, closed up the holes with a waxed substance and waited for them to hatch almost three weeks later.


Of seven chicks injected in-utero, six could see after hatching, said the scientists, whose research is published online Tuesday in the journal Public Library of Science-Medicine.


"The blind animals just stand there, obviously," Semple-Rowland said. "These animals' performance visually was spectacular. Their ability to peck targets, very small ones, was amazing to me."


Among the vision tests is one in which the birds are set near white paper marked with tiny dots. The chicks headed for the paper and began pecking the dots as if they were feed, she said. "They had great binocular vision. We know this because their accuracy was very good."


Still, the treatment isn't yet perfected. By four months of age, all the chickens had lost their sight when light-receptor cells in the retina, which allow humans and other species to see, began to degenerate.


Semple-Rowland said that's because the injected virus appears to have genetically repaired less than half of the light-receptor cells in the birds' retinas, leaving the rest defective. Those defective cells eventually caused their healthy neighbours to degrade.


But she doesn't believe that would happen in children carrying the mutated LCA1 gene - who would be treated after birth, likely any time up to age five - because a gene-transfer therapy would be injected through the eyeball to flood the area directly underneath the retina.


Children with LCA1 can be born blind or have some sight that is gradually lost. There are several types of LCA-related blindness, which affects three in every 100,000 people worldwide, accounting for about 20 per cent of children in schools for the visually impaired, says the Toronto-based Foundation Fighting Blindness of Canada.


"This is very exciting," said Dr. Elise Heon, chief of ophthalmology at Toronto's Hospital for Sick Children, commenting on the research. "It's really a wonderful proof of principle that you can restore visual function in an inherited blinding disorder."


Heon, noting that she sees kids with LCA-related blindness every other week at the Sick Kids vision clinic, said further tweaking of the viral delivery system and testing in larger animals will be needed before this particular therapy can be tried in humans.


Semple-Rowland's work builds on research by other U.S. scientists. In 2000, University of Pennsylvania-led researchers - working with a breed of congenitally blind dog and a different gene, called RPE65 - successfully gave the canines sight by injecting healthy genes into their eyes. That group is gearing up to begin testing the therapy in children with a similar genetic mutation.


"Enabling chickens that can't see to peck and eat after treatment is stunning," said Dr. Jean Bennett, a professor of ophthalmology and developmental biology at the University of Pennsylvania, who was involved in the dog research. "This is proof of concept using a unique vector, animal model and approach. One would hope this could happen in a human."


Heon, calling Semple-Rowland a "visionary" because she fought without funding to keep breeding the blind Rhode Island Reds over the last two decades, said her team's work shines a ray of light beyond just children with LCA-related blindness.


"What it shows is that there's really hope also for other (genetically-related) retinal diseases . . . Now many groups throughout the world will be working on this to target other similar diseases."



http://cnews.canoe.ca/CNEWS/Science/2006/05/22/1592510-cp.html




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