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Scientists are making dramatic strides toward a goal that once seemed almost unimaginable: Restoring limited vision to people affected by a previously irreversible form of blindness caused by an inherited eye disease called retinitis pigmentosa.
In a paper published Monday in the journal Nature Medicine, researchers working with the Paris-based company GenSight Biologics SA reported that a 58-year-old man who was diagnosed with retinitis pigmentosa 40 years ago was able to locate objects placed on a table after receiving an experimental therapy. And New York City-based company Bionic Sight LLC announced in March that four blind people in an early-stage clinical trial are now able to detect light and motion after undergoing a similar treatment. Those results haven’t yet been published.
The patients all had advanced cases of retinitis pigmentosa, which affects more than two million people world-wide. All underwent optogenetic therapy, in which an injection is used to deliver a gene into the eye to boost the light sensitivity of certain cells in the retina, a layer of tissue at the back of the eye. The companies are developing high-tech goggles that process and amplify light in a way that boosts the cells’ ability to send electrical signals to the brain.
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Scientists are making dramatic strides toward a goal that once seemed almost unimaginable: Restoring limited vision to people affected by a previously irreversible form of blindness caused by an inherited eye disease called retinitis pigmentosa. (iStock)
Dr. Anand Swaroop, a senior investigator at the National Eye Institute in Bethesda, Md., called optogenetic therapy an exciting option for some blind people but not a cure. Once sight is lost completely, he said, "Restoring vision that allows high resolution, high sensitivity, and high detection is not simple."
How Optogenetics Tries to Restore Partial Vision
An experimental technique has been shown to restore partial vision in people blinded by a hereditary eye disease known as retinitis pigmentosa.
In normal vision, light hits the retina at the back of the eye. Photoreceptor cells there convert the light into electrical signals that travel through the retina to the ganglion cells. The ganglion cells then send the signals via the optic nerve to the brain. The brain turns those signals into images.
Retinitis pigmentosa causes the photoreceptor cells to break down, resulting in vision loss.
Recent experiments with optogenetic therapies are starting to show some restoration of vision. The therapies deliver a gene to the ganglion cells that makes them sensitive to light.
Patients then wear special goggles, which process the light...
...and amplify it to help the ganglion cells send electrical signals to the brain.
Barry Honig, a participant in the Bionic Sight trial, said that people had often asked him if he would like to be able to see again. "This is the first time I have felt it is attainable," he said.
A 59-year-old father of three living in Tenafly, N.J., Mr. Honig said that tests following the treatment showed he was able to identify objects by sight—distinguishing, for example, the curved shape of a banana from the rounder shape of an apple. He said he was surprised by the improvement in his vision. "Imagine you spend a long time in a dark tunnel and all of a sudden you are back in the light," he said. "You have to adjust."
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New York City-based company Bionic Sight LLC announced in March that four blind people in an early-stage clinical trial are now able to detect light and motion after undergoing experimental therapy. (iStock)
GenSight said it is also developing the therapy as a treatment for macular degeneration, a leading cause of vision loss in people over age 50. Up to 11 million people in the U.S. suffer from the condition, according to the Clarksburg, Md.-based nonprofit BrightFocus Foundation, which funds research on brain and eye diseases.
The use of gene therapy to treat blindness isn’t new. Luxturna, a prescription medicine approved in 2017 by the U.S. Food and Drug Administration, is used in children and adults with a form of retinitis pigmentosa caused by a specific genetic mutation. Editas Medicine of Cambridge, Mass., is testing Crispr gene editing in retinitis pigmentosa patients with a different gene mutation.
But retinitis pigmentosa can be caused by mutations in more than 70 different genes, and doctors say it is too costly and difficult to develop a gene therapy for all of them. "All these patients are left out," said Dr. Sheila Nirenberg, professor at Weill Medical College of Cornell University and Bionic Sight’s founder. "What about them?"
Optogenetics offers the ability to treat blindness caused by retinitis pigmentosa regardless of the specific gene mutation that underlies it. "It is gene-agnostic," said Dr. Brian Brooks, clinical director of the National Eye Institute.
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Restoring vision is a crucial goal for scientists and clinicians, and many other strategies are being pursued in academic labs and companies—including bionic eyes and stem-cell therapies in addition to drugs and optogenetics.
Stem-cell therapy is one option scientists are researching to reverse blindness caused by genetic conditions. (iStock)
In normal vision, light-sensitive cells in the retina known as photoreceptors convert light into electrical signals that travel to nearby ganglion cells. These cells then send the signals via the optic nerve to the brain, which turns them into visual perceptions. In retinitis pigmentosa and similar hereditary retinal disorders, the photoreceptors break down and stop working.
Optogenetic therapy gets around that problem by bypassing the photoreceptors, using the injected gene to confer light sensitivity to the ganglion cells that respond to light beamed into the eye by the goggles.
Vedere Bio Inc. is pursuing a version of optogenetic therapy that doesn’t require goggles. Novartis acquired Vedere Bio, based in Cambridge, Mass., last year and hopes to launch a clinical trial, said Dr. Cynthia Grosskreutz, vice president and global head of ophthalmology at the Novartis Institutes for BioMedical Research.
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"At the end of the day the goal is to get it to patients that need it," she said. "The easier it is for the therapy to be administered, the more patients will have access to the treatments."
In the GenSight trial, an unnamed 58-year-old Frenchman received the optogenetic injection in one eye and was trained to use the goggles. In tests administered 4½ months after the injection, the man was able to perceive and count items placed before him on a table. Ten months after the injection, he felt comfortable using the goggles outside, telling the researchers accompanying him that he could see the white stripes of crosswalks, according to Dr. José-Alain Sahel, an ophthalmologist at the University of Pittsburgh and Sorbonne University and an author of the Nature Medicine paper.
In the GenSight trial, an unnamed 58-year-old Frenchman received the optogenetic injection in one eye and was trained to use the goggles. (iStock)
The current version of the optogenetics technology has some limitations, according to the scientists behind the research. Only a small portion of the patients’ ganglion cells were treated, limiting the potential benefit. The treated patients aren’t expected to regain all of their lost eyesight—they can’t read, drive or recognize faces.
"It is not normal vision," said Dr. Botond Roska of the University of Basel and the Institute of Molecular and Clinical Ophthalmology Basel, an expert in the study of vision and the retina and another author of the paper. "But it gives hope to restore vision that is meaningful."
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Mr. Honig, the father who participated in the Bionic Sight trial, started using a guide dog at 16. His vision dramatically deteriorated over the decades to the point that he could barely see light.
Months after receiving the injection, he said he has noticed improvements in his vision even without the goggles. He can see the shape of a cup when he brings it close to his mouth to take a drink. Looking out the window, he can tell if the sun is out. He doesn’t expect to ever be able to drive. But someday, he said, he hopes the technology will improve enough to allow him once again to see his wife’s dark hair and get at least a rough picture of his children’s faces.
"I am not visually greedy," Mr. Honig said. "That would be amazing."
To read more from The Wall Street Journal, click here.