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September 15, 2009

Gene therapy used to successfully treat color blindness in adult monkeys

UW Health Sciences/UW Medicine

University of Washington (UW) researchers at the UW Medicine Eye Institute have successfully used gene therapy to cure color blindness in adult monkeys. Red-green color blindness, which results from loss of either the red- or green-sensitive visual pigment in the eye, is the most common genetic disorder. One in 12 men and 1 in 230 women are affected, while 1 in 6 women is a carrier of the inherited condition. The work is a culmination of more than eight years of research performed in collaboration with laboratories at the University of Florida and the Medical College of Wisconsin.


The researchers used a computerized test for human color blindness. The test was similar to the well-known testing books in which colored numbers or symbols are concealed in a pattern of dots that look like jellybeans on a plate. Prior to treatment, the monkeys were trained to touch the location of a colored patch hidden among gray dots. Similar to color-blind humans, the monkeys could not distinguish red or green, but following treatment that added the missing visual pigment gene, the monkeys passed the test easily for all colors.


A popular belief has been that “critical periods” for the development of many capacities end prior to adolescence, implying that treatments involving the adult visual system would be impossible. To the contrary, the results of Mancuso and colleagues reported in Nature indicate that in the case of color vision, the nervous system is capable of responding to newly-added sensory input, allowing adult monkeys to respond to colors that they could not see previously.


The results were published today in Nature in the article “Gene Therapy for Red-Green Color Blindness in Adult Primates.” The lead author is Dr. Katherine Mancuso, a postdoctoral student in the UW Department of Ophthalmology. The senior authors are Drs. Jay and Maureen Neitz, a couple internationally noted for their work on animal vision, color vision, color blindness testing, and the genetics of inherited vision disorders. Jay is the E.K. Bishop Endowed Professor of Ophthalmology, and Maureen is the Ray H. Hill Endowed Professor of Ophthalmology.


The success in treating color blindness complements ongoing gene therapy trials for a blinding disorder, Leber’s congenital amaurosis (LCA), a progressive disease that causes cell death and retinal degeneration, Jay Neitz said. The initial phases of the LCA trials are safety studies in which a therapeutic gene was administered to patients with advanced disease. Early results indicate that the treatment is safe, the researchers noted, however, the effectiveness of the therapy for LCA will not be known until younger patients with healthier retinas are treated. In contrast to LCA, retinal degeneration is not associated with color blindness and its successful treatment demonstrates the full potential of gene therapy to restore a visual capacity, according the Neitz’s. They added that, because most vision disorders have a genetic component involving the retina, the encouraging results of both studies open the way to treatments for a broad range of eye diseases.


People with severe forms of color vision deficiency struggle with many everyday tasks that most people take for granted, such as detecting a sunburn or determining when tomatoes are ripe. Color blindness also excludes people from numerous professions. Some obvious examples include employment as police officers, fire fighters, public transit drivers, and pilots. In other professions the requirement is not as obvious, and some people spend years training for careers as designers, geologists, chemists, or ophthalmologists before being excluded by their color blindness. Color-coding is used extensively in education and children can be mistakenly labeled as learning-disabled before it is discovered that they have a color vision deficiency, the Neitz’s said. Maureen became interested in pursing a treatment for color blindness because she has relatives with the condition.


The prospect of ameliorating the problems caused by color blindness makes it an attractive future target for human gene therapy. Because the monkey visual system is similar to that of humans, a human gene was used to replace the missing visual pigment of the monkeys. The scientists said they are optimistic about the future possibility of gene therapy to cure colorblindness in humans. In the same way that few would settle for a black-and-white television or monochrome computer-monitor, it is easy to imagine, they added that many color-blind people would want the cure if there were no risk to their vision or health. While no adverse side-effects were observed in the monkeys, the most important step in moving the treatment forward will be insuring its safety for use in humans. At present, the gene therapy is not available for people.


In addition to Mancuso and Jay and Maureen Neitz, researchers on the gene therapy for color blindness in monkeys are William W. Hauswirth and Quihong Lee of the Department of Ophthalmology and Powell Gene Therapy Center at the University of Florida, Gainesville; Thomas Connor and Matthew Mauck, of the Department of Ophthalmology of the Medical College of Wisconsin in Milwaukee; and James A. Kuchenbecker of the UW Department of Ophthalmolgy.


The research was supported by the National Eye Institute of the National Institutes of Health, the Harry J. Heeb Foundation, the Posner Foundation, the Macular Vision Research Foundation, the Foundation for Fighting Blindness, Hope for Vision, and Research to Prevent Blindness.


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The UW Medicine Eye Institute is dedicated to preventing and treating vision disorders. In addition to its patient care services, the Institute has more than 25 researchers working to understand eye diseases and to find ways to ameliorate them. The UW Medicine Eye Institute is among the top 10 recipients of National Eye Institute funding.