September 17, 2009

Gene Therapy May Cure Color Blindness

Researchers from the University of Washington and the University of Florida have used gene therapy to cure two adult monkeys of color blindness, successfully restoring full color vision to the animals.

Scientists had previously believed it was not possible to manipulate the adult brain in such a way, and that adding new sensory information, such as the visual receptors necessary for perfect color vision, could only be done during the earliest years of life, when the brain is at its most malleable.

But experts now believe the gene therapy treatment used to treat the monkeys, which had been born without the ability to distinguish between the colors green and red, may work for color blind humans as well.  However, further studies are still needed, they say.

Color blindness is the most common genetic disorder in people, affecting millions of people around the world, including about 3.5 million people in the U.S., more than 13 million in India and more than 16 million in China. The condition mostly affects men, leaving about 8 percent of Caucasian men in the U.S. incapable of discerning red and green hues.

Scientists are optimistic that gene therapy has potential as a treatment for adult vision disorders involving cone cells "” the most important cells for vision in humans.

"We've added red sensitivity to cone cells in animals that are born with a condition that is exactly like human color blindness," wrote William W. Hauswirth, Ph.D., a professor of ophthalmic molecular genetics at the UF College of Medicine, in a report about the study.

"Although color blindness is only moderately life-altering, we've shown we can cure a cone disease in a primate, and that it can be done very safely. That's extremely encouraging for the development of therapies for human cone diseases that really are blinding."

"People who are colorblind feel that they are missing out," said Jay Neitz, Ph.D., a professor of ophthalmology at the University of Washington.

"If we could find a way to do this with complete safety in human eyes, as we did with monkeys, I think there would be a lot of people who would want it. Beyond that, we hope this technology will be useful in correcting lots of different vision disorders."

The current breakthrough comes nearly one decade after Neitz and his wife Maureen Neitz, Ph.D., a professor of ophthalmology at the University of Washington and senior author of the study, began working with two squirrel monkeys named Dalton and Sam.

Dalton is named for John Dalton, an English chemist who realized he was colorblind and published the first paper about the condition in 1798.

In addition to teaching the animals, the Neitz research team worked with the makers of a standard vision-testing technique called the Cambridge Color Test to perfect a method the monkeys could use to indicate which colors they were seeing. The tests are similar to those given to schoolchildren throughout the world, in which students are asked to identify a specific pattern of colored dots among a field of dots that vary in size, color and intensity.

The researchers devised a computer touch screen the monkeys could use to trace the color patterns, and rewarded the animals with grape juice when they chose correctly.

Meanwhile, Hauswirth and colleagues at the University of Florida spent years developing a gene-transfer technique that uses a harmless adeno-associated virus to deliver corrective genes to produce a desired protein.

The researchers wanted to produce a substance called long-wavelength opsin in the retinas of the monkeys. This particular type of opsin is a colorless protein that works in the retina to make pigments that are sensitive to red and green.

"We used human DNAs, so we won't have to switch to human genes as we move toward clinical treatments," said Hauswirth.

Roughly five weeks after the treatment, the monkeys began to acquire color vision, seemingly overnight.

"Nothing happened for the first 20 weeks," Neitz said.

"But we knew right away when it began to work. It was if they woke up and saw these new colors. The treated animals unquestionably responded to colors that had been invisible to them."

It took more than 18 months to test the monkeys' ability to discern 16 hues, some of which varied as much as 11-fold in intensity.

"We've had Dalton and Sam for 10 years. They are like our children," Neitz added.

"This species are friendly, docile monkeys that we just love. We think it is useful to continue to follow them "” it's been two years now that they've been seeing in color, and continuing to check their vision and allowing them to play with the computer is part of their enrichment."

The researchers' discovery is the first to address a vision disorder in primates in which all photoreceptors are intact and healthy, providing a hint of gene therapy's full potential to restore vision.

About 1 in 30,000 Americans have a hereditary form of blindness called achromatopsia, which causes nearly complete color blindness and extremely poor central vision.

"Those patients would be targets for almost exactly the same treatment," said Hauswirth, who is also involved in a clinical trial with human patients to test gene therapy for the treatment of Leber congenital amaurosis, a form of blindness that strikes children.

Even in common types of blindness, such as age-related macular degeneration and diabetic retinopathy, vision could potentially be rescued by targeting cone cells, he said.

"The major thrust of the study is you can ameliorate if not cure color blindness with gene therapy," said Gerald Jacobs, Ph.D., a research professor of psychology at the University of California, Santa Barbara, who was not involved in the study.

"There are still questions about safety, but in these monkeys at least, there were no untoward effects. Those who are motivated to ameliorate their color defect might take some hope from the findings," he said.

"This is also another example of how utterly plastic the visual system is to change."

"The nervous system can extract information from alterations to photopigments and make use of it almost instantaneously."

The findings were published online on Wednesday in the journal Nature.  Ã‚


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