Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. Through this new study, scientists at the University of Florida evaluated the safety and preliminary efficacy of a newly developed gene therapy.
Scientists found that the therapy restored functional vision to most patients with the rare, inherited blindness called LCA1.
LCA1 is caused by having two defective copies of the gene GUCY2D, which is required for the light-sensitive cells in the eyes to function properly. People with the disease tend to have severely impaired vision, which makes it difficult or impossible to drive, read, or navigate the world visually.
In a small trial study, after the treatment, one patient saw her first star, another saw snowflakes for the first time, and other patients were newly able to navigate outsiders to read the labels on their child’s Halloween candy.
Fifteen patients were enrolled for the study at the University of Pennsylvania or Oregon Health and Science University. To identify the safest and most effective dose, they received one of three different doses of the therapy, which was given through a surgical injection into the retina of one eye.
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Scientists followed the patients for a year to test their vision in the treated eye compared to the untreated eye. Subjects who received higher doses saw more significant improvements in their vision.
Those who received the highest dose of the gene therapy improved their light sensitivity 10,000-fold. They could read more lines on an eye chart. The treatment also improved their ability to navigate a standardized maze.
Shannon Boye, Ph.D., chief of the Division of Cellular and Molecular Therapy at UF, co-author of the study, and co-founder of Atsena Therapeutics, said, “This is the first time that anyone with LCA1 has ever been treated, and we showed a very clean safety profile and efficacy. These results pave the way for advancing the therapy in a phase 3 clinical trial and eventually commercializing it.”
In collaboration with her husband, Sanford Boye, Shannon Boye’s lab developed the virus-based transport system essential for delivering functioning copies of the GUCY2D gene into the correct cells in the eyes.
“Most pharmaceutical companies are not interested in treating these rare diseases because they are not strong revenue generators. But we think these patients deserve attention because we have treatments that work and improve their quality of life.”
This gene therapy is expected to last indefinitely. It requires just a single treatment per eye. So far, they have seen visual improvements last at least five years.
Journal Reference:
- Paul Yang, Laura P Pardon, Prof Allen C Ho, Prof Andreas K Lauer, Dan Yoon, Prof Shannon E Boye, PhDd∙ et al. Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study. The Lancet. DOI: 10.1016/S0140-6736(24)01447-8