Gene therapy restores function to brain's visual center

PHILADELPHIA — Using gene therapy to restore retinal activity to patients with Leber's congenital amaurosis may also help restore function to the brain's visual cortex, assisting in restoring vision, according to a study by researchers at the University of Pennsylvania.

Geoffrey K. Aguirre, MD, PhD, an assistant professor of neurology at the university, and colleagues used functional MRI to measure the brain activity in blind dogs that were born with a genetic mutation in the RPE65 gene. That gene is an essential molecule in the retinoid-visual cycle and the same mutation in this gene causes Leber's congenital amaurosis in humans, according to a press release from the university announcing the study findings.

The researchers found that somatic gene therapy delivered to the retina significantly increased light response in dogs' visual cortices. In particular, a dog that had been blind for the first 4 years of life recovered visual brain function. In another animal, the visual recovery persisted for at least 2.5 years after treatment, suggesting that the recovery has some level of permanence, according to the release.

The researchers also examined the structure and function of the visual cortex in human patients with Leber's congenital amaurosis caused by the same mutation in RPE65. They found that, although patients' visual cortices did not respond to dim lights, they showed activity comparable to normal when exposed to higher intensity light.

"Existence of functional potential both in the eye and brain are prerequisites for successful gene therapy in all forms of [Leber's congenital amaurosis]," Artur V. Cideciyan, PhD, research associate professor of ophthalmology, said in the release. "In the RPE65 form of the disease, we now have evidence for both, and treatment at the retinal level has the hope of recovery of useful vision in patients."

The study is published online in PLoS Medicine.