Gene Therapy Gives Vision to Visually Impaired Patients Since Childhood, Study Reveals

A single shot of an experimental RNA therapy brought the vision to a patient suffering from a rare genetic type of childhood blindness.

Results of this gene-editing study done at the University of Pennsylvania Perelman School of Medicine were revealed in a paper published in Nature Medicine on April 1. Findings show that the procedure led to a significant change at the fovea, a core point of human central vision.

Gene Therapy Enhances Retinal Abilities

Patients part of the study took an intraocular shot of the antisense oligonucleotide sepofarsen. This RNA molecule increases normal CEP290 levels in the photoreceptors of the eye, enhancing retinal abilities under day vision conditions.

This remedy was intended for patients with the retinal disorder Leber congenital amaurosis (LCA) having a CEP290 mutation-a commonly affected gene among patients suffering from the illness. Patients suffering from this form of LCA would have a severe visual impairment that begins at infancy.

According to researchers, the findings would set a new standard for possible biological improvements. Co-lead author Artur Cidecyan, Ph.D., who is a research professor of Ophthalmology at Penn Medicine's Science Eye Institute said in the study: "Importantly, we established a comparator for currently-ongoing gene-editing therapies for the same disease, which will allow comparison of the relative merits of two different interventions."

In the study, researchers discovered that repeated shots of sepofarsen every three months led to a significant progression in vision gain in 10 patients. The eleventh patient, who was examined in a 15-month period and received just one shot of sepofarsen, had no night vision, small visual fields, and reduced visual acuity. After receiving the initial dose, the patient decided not to take the quarterly maintenance doses since continued shots increase the risk for cataracts.

Remarkable Vision Improvement Months After Injection

After just a single dose of sepofarsen, remarkable improvements in visual functions and retinal structure were observed, marking a huge biological effect from the treatment. A key discovery from the study was that this biological effect had been relatively slow when the shot was first given. But researchers observed vision improvement after a month, with the patient's vision reaching its most remarkable state after two months or more. Quite strikingly, these vision improvements sustained even when tested 15 months after the injection.

These strong visual improvements were unexpected, say, researchers, who said their findings could offer implications for addressing ciliopathies, which as a disease category linked to genetic mutations that decode defective proteins, which leads to an abnormal function of the cilia, a sensory organelle on cells.

Researchers further noted that this would provide an "exciting direction for RNA antisense therapy." They added that the unexpected stability of the patient's ciliary transaction zone would lead to proper dosing schedules for sepofarsen, and other cilium-targeted treatments.

A reason behind the effectivity of antisense oligonucleotide in treating this rare form of blindness is that the RNA molecules are small enough to penetrate the cell nucleus, but not cleared quickly, as such remaining long enough to do their work.

Researchers plan gene-specific treatments for presently incurable blindness from inherited retinal disorders.

In the UK, charity group Fight For Sight has likewise funded a parallel study at the University College London (UCL) on the use of gene therapy in treating LCA, News Medical reported.

Read more news and information on Gene Therapy on Science Time.