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Twelve months after receiving an experimental gene therapy for a rare, inherited form of blindness, a patient discovered that she could read an illuminated clock in the family car for the first time in her life. The unexpected findings suggest that the brain can adapt to new sensory capacity, even in people who have been blind since birth.

The patient, who remains anonymous, suffers from a disease called Leber congenital amaurosis, in which an abnormal protein in sufferers’ photoreceptors severely impairs their sensitivity to light. “It’s like wearing several pairs of sunglasses in a dark room,” says Artur Cideciyan, a researcher at the University of Pennsylvania in Philadelphia, who oversaw the trial.

At the start of the study, physicians injected a gene encoding a functional copy of the protein into a small part of one eye–about eight-to-nine millimeters in diameter–of three patients, all in their twenties and blind since birth. In preliminary results published last year, Cideciyan and colleagues found that all three patients showed substantial improvements in their ability to detect light three months after treatment.

The researchers have now published new results of the study in the journal Human Gene Therapy, showing that these improvements remained stable after one year. And in a letter to the New England Journal of Medicine, they describe surprising gains in one patient’s vision. “It was unexpected because the major improvement of vision had occurred within weeks after the treatment,” says Cideciyan.

Probing further, the researchers found that the patient appeared to be using the treated part of her eye like a second fovea–the part of the retina that is most densely populated with photoreceptors and is typically used for detailed vision, such as reading. The patient could detect dimmer light using the treated region than she could with her natural fovea. “We realized she was slowly adapting to her newfound vision by subconsciously focusing her attention to the treated area as opposed to the untreated central fovea,” says Cideciyan. “It suggests that there is a plasticity, an ability to adapt in the adult visual brain.”

“It’s very encouraging,” says Kang Zhang, an ophthalmologist and director of the Institute for Genomic Medicine at the University of California, San Diego, who was not involved in the study. “The formation of almost another vision center has implications as we go forward for patients with congenital blindness. They might not be able to use their normal fovea, but they might be able to develop a new center of vision.”

Researchers now plan to study other patients in the trial to determine if they have experienced similar improvements. They also hope to figure out how to accelerate these gains, perhaps by using visual training targeted to the area treated with gene therapy.

The scientists also say that the fact that patients’ visual improvements held for a year after injection is promising. “It means that for congenital or childhood blindness,” says Zhang, “there is the potential to at least stabilize, if not improve, visual function.”

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Credit: Sarah Kiewel/University of Florida

Tagged: Biomedicine, blindness, gene therapy, retinitis pigmentosa

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