Better vision in sight
By Czerne M. Reid
A new gene therapy method developed by UF researchers has the potential to reverse a common form of blindness that strikes young children and adults. The technique works by replacing a malfunctioning gene with a normal working copy that supplies a protein necessary for light-sensitive cells in the eye to function.
Several complex and costly steps remain before the gene therapy technique can be used in humans, but once at that stage, it has great potential to change lives. The findings were published Jan. 23 in the Proceedings of the National Academy of Sciences online.
“Imagine that you can’t see or can just barely see, and that could be changed to function at some levels so that you could read, navigate, maybe even drive — it would change your life considerably,” said study co-author William W. Hauswirth, Ph.D., the Rybaczki-Bullard professor of ophthalmology in the UF College of Medicine and a professor and eminent scholar in the department of molecular genetics and microbiology and the UF Genetics Institute. “Providing the gene that’s missing is one of the ultimate ways of treating disease and restoring significant visual function.”
The researchers tackled a condition called X-linked retinitis pigmentosa, a genetic defect passed from mothers to sons. Girls carry the trait, but do not have the kind of vision loss seen among boys. About 100,000 people in the U.S. have a form of retinitis pigmentosa, characterized by initial loss of peripheral vision and night vision, which eventually progresses to tunnel vision, then blindness.
The UF researchers previously had success pioneering the use of gene therapy in clinical trials to reverse a form of blindness known as Leber’s congenital amaurosis. About 5 percent of people who have retinitis pigmentosa have this form, which affects the eye’s inner lining.
The X-linked form of retinitis pigmentosa addressed in the new study is the most common and is caused by degeneration of light-sensitive cells in the eyes, known as photoreceptor cells. It starts early in life, so although affected children often are born with sight, they gradually lose vision.
“These children often go blind in the second decade of life, which is a very crucial period,” said co-author Alfred S. Lewin, Ph.D., a professor in the UF College of Medicine department of molecular genetics and microbiology and a member of the UF Genetics Institute. “This is a compelling reason to try to develop a therapy, because this disease hinders people’s ability to fully experience their world.”
Both Lewin and Hauswirth are members of UF’s Powell Gene Therapy Center.
The UF researchers and colleagues at the University of Pennsylvania performed the technically challenging task of cloning a working copy of the affected gene into a virus that transports it to the appropriate part of the eye. They also cloned a genetic “switch” that would turn on the gene once it was in place, so it could start producing a protein needed for the damaged cells to function.
After laboratory tests proved successful, the researchers expanded their National Institutes of Health-funded studies and were able to cure animals in which X-linked retinitis pigmentosa occurs naturally. The researchers plan to repeat their studies on a larger scale over a longer term and make a version of the virus that is safe in humans. Then, a pharmaceutical grade of the virus would have to be produced and tested before moving into clinical trials in humans.