GENE THERAPY SHOWS IMPROVEMENT IN VISION FOR CONGENITAL BLINDNESS

A new gene therapy, ATSN-101, has shown promising results in improving vision and light detection in both adults and children with a rare form of congenital blindness called Leber congenital amaurosis (LCA) 1. This type of LCA is caused by mutations in the GUCY2D gene. The early-phase clinical trial, published in “The Lancet”, involved 15 patients and demonstrated significant improvements, particularly in light detection.

In this trial, after 12 months of treatment, patients who received the highest dose of the therapy showed improved ability to see finer details. For example, there was an improvement of about 8 letters on an eye test chart, which equates to nearly two lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. While the improvements in visual sharpness (acuity) were modest, the ability to detect light, especially in long-dormant photoreceptors (rods and cones in the retina), was the standout finding.

Dr. Artur Cideciyan, one of the lead researchers, explained that even after decades of dysfunction, the photoreceptors in the patients' eyes began functioning again within 8-10 days after receiving the gene therapy. This suggests that even long-standing congenital conditions might be treatable, as the cells responsible for vision haven't completely lost their ability to function.

Light Detection Improvements

The most exciting part of the study was the significant improvements in light detection. For example, in the dark-adapted full-field stimulus test (FST), which measures the dimmest light detectable in darkness, patients who received the highest dose of the therapy showed significant improvement—some by more than 10,000 times. Six out of the nine high-dose patients had major improvements in their ability to detect light.

Dr. Darius Moshfeghi, a retina specialist, commented on the study, noting that this was the first time gene therapy had shown such a dramatic improvement in vision function for an inherited retinal disease. This finding gives hope for treating other similar diseases, as it shows that photoreceptors can regain function even after being inactive for years.

Gene Therapy and the Procedure

ATSN-101 is a gene therapy that uses a recombinant AAV5 vector containing the human GUCY2D gene. This therapy is delivered through surgery where a retina specialist injects the gene vector under the retina. Three doses were tested in the trial, and after seeing initial improvements, a higher dose was administered to six additional patients (three adults and three children).

Safety Concerns and Learning Curve

Although the therapy showed promise, there were some side effects related to the surgery. The study reported 68 treatment-related adverse events, including eight patients experiencing low eye pressure (hypotony) and complications such as macular holes and retinal detachment in a few patients. While these issues were treatable, they highlight the need for improved surgical techniques and learning curves in administering the therapy.

Overall, the results are very encouraging for the future of gene therapy in treating congenital blindness and other inherited retinal diseases, offering hope that dormant photoreceptors can be revived to restore vision.

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