Study shows efficacy of gene therapy in preschool children with LCA2

Leber congenital amaurosis (LCA) is a rare genetic eye disorder that causes low vision or blindness from birth. At least 20 genetic types of LCA have been described, with type 2 stemming from mutations in both copies of the RPE65 gene. Luxturna (voretigene neparvovec, Novartis), the first and only FDA-approved gene therapy treatment for inherited retinal diseases, provides a working RPE65 gene to act in place of a mutated RPE65 gene. Luxturna is administered as a surgical injection beneath the retina of each eye on separate days. Luxturna proved successful as a treatment for LCA2 in preschool children, as shown by a study presented at the FLORetina-ICOOR meeting. The study was carried out at the University of Munich in a group of five children with RPE65 mutation-associated  LCA2, the youngest to be treated with Luxturna in Germany so far. “There are challenges in delivering this treatment in children,” Siegfried G. Priglinger, MD, PhD, said, but the treatment was successfully delivered in all five children, with rewarding outcomes. Preoperatively, most of the children were incapable of eye contact from birth and were conspicuously looking toward light sources such as windows and lamps. They showed disorientation in the dark, were clumsy, and had difficulty catching balls. “Just a few weeks after gene therapy, they are significantly better orientated in the twilight, additional light sources in the room are no longer necessary, the grip is more secure, and an increased field of view is observed while playing,” Priglinger said. Videos demonstrated the progress of these children in recognizing chart symbols, and one child, 3 months after surgery, was shown to cycle alone along a route in the dark without any help.

Objective parameters also showed improvement, with significant visual acuity gain in all children except one, with the highest gain in one child who achieved 20/20 vision. Visual field testing, which measures peripheral vision, due to the young age, was possible in only two children, aged 4 years and 5 years, and showed notable improvement after the treatment.

No case of chorioretinal atrophy was reported, a complication that has previously been observed with Luxterna injections for LCA, but one case of atrophy of the retinal outer layer occurred at the injection site. It was first seen 4 weeks after the treatment, with no change until the last follow-up visit at 32 months.

Edited by Suditi Kedambadi and M. Kaplan, PhD. 

Source: Healio, December 19, 2023; see source article