A new approach to gene therapy for retinitis pigmentosa may help patients with advanced disease regain vision regardless of which genetic mutation is causing the condition.

An optogenetic therapy known as MCO-010 does not target a particular mutation. Instead, bipolar cells in the retina are genetically modified to produce a photosensitive protein that may compensate for a loss of typical photoreceptors. 

The FDA approved the first gene therapy for retinitis pigmentosa in 2017, but the treatment is limited to patients with mutations in both copies of the RPE65 gene. The therapy, Luxturna, delivers a normal copy of the gene into retinal cells. 

Fewer than 2% of patients with clinically diagnosed retinitis pigmentosa in the United States have this mutation, however, studies have found. The condition, which affects roughly 1 in 4000 people worldwide, comprises a group of inherited disorders, and dozens of genes have been implicated in its pathogenesis. 

Patients with retinitis pigmentosa typically experience progressive loss of peripheral vision and difficulty with night vision. The disease can lead to loss of central vision.

MCO-010

In September, researchers discussed 3-year follow-up data from patients who received MCO-010 in a phase 2b trial in separate presentations at the EURETINA Congress and at the annual scientific meeting of The Retina Society. 

Samarendra Mohanty, PhD, the president and chief scientific officer of Nanoscope Therapeutics, the company developing MCO-010, also described the treatment during a virtual meeting last month held by the FDA’s Center for Biologics Evaluation and Research about facilitating the development of cell and gene therapies. 

No serious adverse events have been reported in the clinical trials of MCO-010, Mohanty reported at the meeting.

Nanoscope announced in July it has begun submitting a Biologics License Application for MCO-010 to the FDA. The application is expected to be fully filed in early 2026, the company said.

One-Time Injection

MCO-010 is administered via a one-time intravitreal injection, with adeno-associated virus 2 (AAV2) delivering a multi-characteristic opsin transgene.

The gene therapy transduces cells to produce a photosensitive protein designed to overcome limitations of other opsins that have been used in optogenetics, such as slow kinetics and only partial activation in ambient light. 

The MCO-010 opsin is likely “one of the most synthetic, non-mammalian proteins ever expressed in a human,” researchers reported in March, but they did not identify any significant safety issues when the treatment was administered to four blind patients in an open-label study. 

During the 52-week study, patients experienced improvements in their vision, ability to discriminate shapes, and mobility.

Researchers then conducted the randomized, double-masked phase 2b RESTORE trial, in which nine participants received low-dose MCO-010, nine received a higher dose of MCO-010, and nine received a sham injection. 

Nanoscope in March 2024 announced positive top-line results from the trial. At 52 weeks, best-corrected visual acuity (BCVA) was significantly improved in the high-dose (0.337 LogMAR; P = .021) and low-dose (0.382 LogMAR; P = .029) treatment groups, compared with the control group (0.050 LogMAR).

At The Retina Society meeting in September, researchers presented results focused on longer term follow-up of RESTORE participants. At 152 weeks, participants in the low-dose group experienced a mean improvement in BCVA from baseline of 0.453 ± 0.140 LogMAR. The group who received the high dose had mean improvement in BCVA of 0.264 ± 0.112 LogMAR. 

“Durable efficacy and long-term tolerability are meaningful for patients suffering from irreversible, progressive vision loss due to RP, and underscore the potential of MCO-010 to redefine the standard of care for these patients,” Mohanty said in a news release about the data. 

The gene therapy may find other indications as well. Nanoscope also is evaluating MCO-010 in Stargardt disease and plans to examine its use in geographic atrophy and Leber congenital amaurosis. The company said it is working with European regulators to have MCO-010 evaluated as a potential treatment for non-syndromic and syndromic rod- and cone-dominant dystrophies and macular dystrophies. 

While investigators continue work on gene therapies that target specific mutations, other mutation-agnostic therapies for retinitis pigmentosa are in development. These include Ocugen’s OCU400, Ray Therapeutics’ RTx-015, Restore Vision’s RV-001, and AbbVie’s RST-001. GenSight in 2021 reported it had used optogenetic therapy to partially restore vision in a patient with the condition. With that technique, the patient wore special goggles to see. MCO-010 does not rely on external equipment.