Scientists have discovered a novel gene therapy that results in a 100-fold improvement in the eyesight of patients that have Leber congenital amaurosis.
Leber congenital amaurosis, or LCA1, is a rare inherited condition that causes patients to lose much of their eyesight in early childhood. The condition results from a mutation of the GUCY2D gene, which produces essential proteins critical to vision.
The study, published in The Lancet, describes a gene therapy that corrects this mutation, leading to a 100-fold improvement in most participants, and even a 10,000-fold improvement in some after receiving the highest dose.
"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," said Artur Cideciyan, Ph.D., a research professor of Ophthalmology at the Center for Hereditary Retinal Degenerations. "One patient reported for the first time being able to navigate at midnight outdoors only with the light of a bonfire."
A total of 15 participants with severe vision loss participated in the study in which they were given the gene therapy ATSN-101, adapted from the AAV5 microorganism. During the multi-phase study, improvements were noted very quickly. Most often improvements were observed within the first month and remained for 12 months after the therapy was applied.
"Even though we previously predicted a large vision improvement potential in LCA1, we did not know how receptive patients' photoreceptors would be to treatment after decades of blindness," said Cideciyan. "It is very satisfying to see a successful multi-center trial that shows gene therapy can be dramatically efficacious."
"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," said Omas S. Aleman, MD, Research Professor in Ophthalmology at the Center for Hereditary Retinal Degenerations.
The next steps for the team will include conducting a randomized trial to achieve clinical use approval.