New Hope in Restoring Vision to People With Rare Inherited Blindness

For many people, seeing clearly is only a dream. But now people with a rare inherited condition that causes them to lose much of their vision during  childhood, there is new hope that their vision could be restored.

A new study published in The Lancet showed that participant’s of  a gene editing clinical trial displayed marked improvement of their vision to the tune of 100 times better. Some even experienced a 10,000-fold improvement after they received the highest does of the therapy.

“That 10,000-fold improvement is the same as a patient being able to see their surroundings on a moonlit night outdoors as opposed to requiring bright indoor lighting before treatment,” the study’s lead author, Artur Cideciyan, PhD, a research professor of Ophthalmology and co-director of the Center for Hereditary Retinal Degenerations, said in a press release from Penn Medicine News.

Inherited blindness
The 15 participants, 12 adults and three pediatric patients, of the Phase 1/2 trial all have Leber congenital amaurosis (LCA1) which affects less than 100,000 people worldwide, according to the press release.  The condition is the result of mutations in the GUCY2D gene – which is essential to produce proteins that are critical for vision – and causes sight loss in very young children.

The trial tested different dosages of the gene therapy ATSN-101 which was surgically injected into the retinas of one eye of each of the patients. The adult participants received one of three differing dosages; low, mid, and high. Evaluations were done between each level of the therapy.

In the second phase of the study, the participant’s – both adults and children – only received high doses. Improvements in vision were already noticed in the first month and lasted for 12 months.

Impressive results
All of the study’s participants had severe vision loss with the best measure being 20/80, according to Ophthalmology Times. Before the gene therapy, there wasn’t much that could be done to improve vision because glasses were ineffective.

While improvements were expected, researchers did not know what to expect because patients had all experienced decades of blindness. Two of the nine patients who received the maximum dosage, showed an astonishing 10,000-fold improvement in vision.

The trial also looked at the safety of using gene therapy. While some patients experienced side effects including conjunctival hemorrhage and eye inflammation that was cleared up by steroids, there were no serious side effects.

This successful trial follows another ophthalmological trial at Penn that restored vision on some patients with a different form of LCA by using CRISPR-Cas9 gene editing. That study was co-led by one of the new study’s co-authors, Tomas S. Aleman, MD, the Irene Heinz-Given and John LaPorte Research Professor in Ophthalmology and co-director with Cideciyan of the Center for Hereditary Retinal Degenerations.

“The treatment success in our most recent clinical trials together with our earlier experience brings hope for a viable treatment for about 20 percent of infantile blindness caused by inherited retinal degenerations,” Aleman said in the press release.

 “The focus now is on perfecting the treatments and treating earlier manifestations of these conditions once safety is confirmed. We hope similar approaches will lead to equally positive outcomes in other forms of congenital retinal blindness.”