AAO 2024: New gene therapy shows promise for treatment of retinitis pigmentosa

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New research unveiled today at the 128th annual meeting of the American Academy of Ophthalmology in Chicago reveals that a novel gene therapy may improve vision in individuals with severe vision loss due to retinitis pigmentosa, a progressive inherited retinal disease for which no cure exists.

According to researchers, op to 50 percent of patients in the study gained three lines of vision on a standard eye chart. Although not all patients responded to the treatment, these findings provide a significant breakthrough for those affected by retinal degeneration.

“We are on the verge of a transformative therapy for patients with advanced vision loss,” Allen C. Ho, MD, director of Retina Research and Co-Director of the Retina Service at Wills Eye Hospital, said in a news release. “These results give both patients and ophthalmologists renewed hope that an effective treatment is within reach.”

Retinitis pigmentosa affects an estimated 1.5 million people globally. The disease progressively damages the retina, leading to the breakdown of photoreceptor cells responsible for sight. This typically starts with night blindness and advances to the loss of peripheral, color, and central vision.

Ho and his team are exploring the use of optogenetics to activate retinal cells that survive after photoreceptor cells are lost. The therapy, administered as a single intravitreal injection, delivers the Multi-Characteristic Opsin (MCO) gene to these remaining cells, enabling them to function as new light-sensing cells, compensating for the lost photoreceptors.

This investigational treatment, known as MCO-010, stands apart from earlier optogenetic therapies that required patients to wear high-tech goggles. MCO-010 eliminates the need for external devices or high-intensity light, simplifying the approach and expanding its potential usability.

MCO-010 is also distinct from Luxturna (voretigene neparvovec), the first FDA-approved gene therapy for retinitis pigmentosa, which is specific to mutations in the RPE65 gene, representing only a small fraction of cases. In contrast, MCO-010 is mutation-agnostic, meaning it targets retinal degeneration caused by a range of genetic mutations, potentially broadening its application to other conditions such as macular degeneration and Stargardt disease.

Ho is presenting100-week results from a randomized, controlled Phase 2b/3 trial of MCO-010, which included patients with advanced vision loss—most of whom had only light perception or worse. A total of 27 participants were randomized to receive either high- or low-dose treatment, or a sham procedure. Results demonstrated statistically significant improvements in visual acuity at 52 and 76 weeks, with up to 50 percent of treated patients gaining at least three lines of vision without any significant adverse effects.

“The level of visual improvement we observed in this trial is unprecedented for such a diverse patient population,” Dr. Ho said. “Although not all participants responded to the therapy, the fact that 40 to 50 percent gained significant vision, such as going from light perception to 20/400, is remarkable.”

Nanoscope Therapeutics, the developer of MCO-010, is preparing to submit a Biologics License Application to the FDA in early 2025. The treatment has already received Fast Track designation from the FDA.

“We are committed to making MCO-010 available to ophthalmologists and their patients as soon as possible,” added Dr. Ho, who also serves as Chief Medical Advisor for Nanoscope. “We are working closely with the FDA on the design of a Phase 3 trial for Stargardt macular degeneration, with preparations already underway.”

Ho concluded this gene therapy represents a new avenue for treating retinitis pigmentosa and potentially other retinal degenerative diseases, offering hope where there was once little.