100x improvement in sight seen after gene therapy trial

Key Takeaways

• The vision of people with Leber congenital amaurosis Type 1 was 100 times better after they received gene therapy to address the genetic mutation causing the condition.
• Moving forward, approval of this experimental medicine for clinical use requires another trial, where participants are randomized to a treatment dose and both patients and those investigating the trial not knowing who gets what.

The vision of people with a rare inherited condition that causes them to lose much of their sight early in childhood was 100 times better after they received gene therapy to address the genetic mutation causing it. Some patients even experienced a 10,000-fold improvement in their vision after receiving the highest dose of the therapy, according to researchers from the Perelman School of Medicine at the University of Pennsylvania, who co-led the clinical trial published in The Lancet. 

A total of 15 people participated in the Phase 1/2 trial, including three pediatric patients. The trial tested different dosage levels of the gene therapy, ATSN-101, which was adapted from the AAV5 microorganism and was surgically injected under the retina.  Each patient had Leber congenital amaurosis as the result of mutations in the GUCY2D gene, which is essential to producing proteins critical for vision. This specific condition, which affects less than 100,000 people worldwide and is abbreviated as LCA1, causes significant amount of vision loss as early as infancy.

Before the therapy, all subjects had severe vision loss with their best measure of vision being equal or worse than 20/80 — meaning if a typically-sighted person could see an object clearly at 80 feet, these patients would have to move up to at least 20 feet to see it. Glasses provide limited benefit to these patients because they correct abnormalities in the optical focusing ability of the eye and are unable to address medical causes of vision loss, such as genetic retinal diseases like LCA1.

Improvements were noticed quickly, often within the first month, after the therapy was applied and lasted for at least 12 months. Observations of participating patients are also ongoing. Three of six high-dosage patients who were tested to navigate a mobility course in varying levels of light achieved the maximum-possible score. Other tests used eye charts or measured the dimmest flashes of light patients perceived in a dark environment. Of the nine patients who received the maximum dosage, two had the 10,000-fold improvement in vision.

Moving forward, approval of this experimental medicine for clinical use requires another trial, where participants are randomized to a treatment dose and both patients and those investigating the trial not knowing who gets what. Through that, any possible bias in results could be avoided.

Edited by Miriam Kaplan, PhD

Source:

University of Pennsylvania School of Medicine, ScienceDaily, September 6, 2024; see source article