Gene Therapy Restores Some Vision in Colorblind Children

Study suggests gene therapy may effectively treat young children who were born colorblind via pathways connecting the brain and the retina.

Gene therapy was able to partially restore cone function in colorblind children, according to research conducted by the University of London published in Brain. Achromatopsia affects rods and cone cells, both photoreceptors in the eyes. The disease, which is a result of gene variants, prevents cone cells from signaling to the brain and causes colorblindness, poor overall vision, and sensitivity to bright light.

"In our trials, we are testing whether providing gene therapy early in life may be most effective while the neural circuits are still developing. Our findings demonstrate unprecedented neural plasticity, offering hope that treatments could enable visual functions using signaling pathways that have been dormant for years,” said co-lead author Michel Michaelides of the UCL Institute of Ophthalmology and Moorfields Eye Hospital, in a press release

Investigators have been researching ways to activate the cone cells and recover color vision. The 2 trials are examining therapies targeting a different gene and to test its safety and efficacy in improving vision.

In the study, the investigators examined 4 individuals aged 10 to 15 years who have achromatopsia. After receiving gene therapy in only 1 eye, investigators evaluated the efficacy of the treatment. Using a functional magnetic resonance imaging (fMRI) brain scan, the study authors pinpointed changes in patient post-treatment visual function by separating their post-treatment cone signals from existent rod-driven signals.

Following the brain scan, the team used a “silent substitution” technique to separately stimulate rods or cones to test the effects of the treatment. They compared the results of the study with data from 9 untreated patients and 28 patients with normal vision.

Prior to the test, no child had normal cone function on any test. After treatment, the results were similar to those of patients with normal vision. Between 6- and 14-months post-treatment, 2 of the 4 participants showed signs of cone-mediated signals in the visual cortex of the brain from the treated eye.

Those same 2 children also showed a difference in cone-supported vision. After taking a psychophysical test, their results showed that the treated eye could see multiple levels of contrast.

"Our study is the first to directly confirm widespread speculation that gene therapy offered to children and adolescents can successfully activate the dormant cone photoreceptor pathways and evoke visual signals never previously experienced by these patients,” said lead author Tessa Dekker, of the UCL Institute of Ophthalmology, in a press release.

At the time of this study, researchers were conducting additional phase 1 and 2 trials to test the neural pathways of the cones.

"We are still analyzing the results from our two clinical trials, to see whether this gene therapy can effectively improve everyday vision for people with achromatopsia. We hope that with positive results, and with further clinical trials, we could greatly improve the sight of people with inherited retinal diseases," Michaelides said in the press release.

Reference

University College London. Gene therapy partly restores cone function in two completely colorblind children. Science Daily. August 24, 2022. Accessed on September 2, 2022.