EURETINA 2026: Optogenetic therapy MCO-010 aims to restore vision in advanced macular disease

At the 26th EURETINA Congress in Vienna, Austria, Jordi Monés, MD, PhD, presented the rationale for using optogenetic therapy with sonpiretigene isteparvovec (MCO-010; Nanoscope Therapeutics) to treat macular dystrophies and macular degeneration.

An unmet need in advanced disease

Current therapies for inherited retinal diseases (IRDs) and macular degeneration aim to slow progression and prevent further vision loss. According to Monés, none can treat advanced cases by restoring vision, and some IRD therapies also depend on the specific gene involved.

The ideal therapy, Monés said, would restore vision in patients with advanced disease. It would also be gene-agnostic, meaning it could treat any condition regardless of which gene caused the outer retinal atrophy. He described these as the fundamentals of optogenetic therapy.

Mechanism of action

Sonpiretigene isteparvovec is a gene therapy that uses an adeno-associated virus serotype 2 (AAV2) vector to transfect retinal bipolar cells with an opsin. The opsin makes bipolar cells able to detect light and convert it into electrical signals, which bypasses the missing photoreceptors.

Clinical and preclinical results

In legally blind patients with retinitis pigmentosa (RP), Monés reported a clinically meaningful and significant gain of 0.3 logMAR, or approximately 3 lines, with a very safe profile. These results led to testing the therapy in patients with Stargardt disease. Vision in the macular phenotype improved by about 12 letters, and by 20 to 30 letters with a magnifier. Monés said the safety profile was again very good.

The therapy is now also directed at geographic atrophy (GA). Investigators developed a new non-human primate model in which OCT-based laser injuries selectively targeted the outer retina, and tested the drug in it. The opsin was expressed in more than 70% of those cells. Monés described this as anatomical success, with additional physiological improvement on multifocal electroretinography (ERG).

Next steps

Based on these data, the plan is to start a large phase 2 trial in Stargardt disease and in GA. Monés said treatment would begin in legally blind patients. Once confidence in safety is established in that group, treatment would extend to patients with less severe vision loss.

From slowing loss to restoring vision

“The biggest key takeaway is that we may have a therapy that can restore vision,” Monés said. He contrasted this with existing therapies, which aim only to limit vision loss. He also noted that patients with advanced disease have had no clinical trials or valid therapy for decades.

“Improving vision is something that we could not imagine a few years ago,” he said, adding that “it’s not science fiction anymore.”