An optogenetic approach to treating geographic atrophy

Sonpiretigene isteparvovec (MCO-010; Nanoscope Therapeutics), an optogenetic therapy originally developed for retinitis pigmentosa (RP), is moving toward a first direct-to-phase 2 randomized, controlled trial in geographic atrophy (GA), according to Jordi Monés, MD, PhD, director of Institut de la Màcula in Barcelona, Spain, and adjunct professor at the John A. Moran Eye Center, University of Utah in Salt Lake City. Monés discussed the unpublished trial design at the American Society of Retina Specialists (ASRS) 2026 annual meeting, presenting the concept publicly for the first time. The clinical trial is expected to begin later this year.

Monés described two defining features of the therapy. First, it is agnostic to the underlying gene mutation or cause of photoreceptor loss. Second, unlike most retinal degeneration therapies aimed at slowing further loss, this approach is designed to restore vision already lost. Monés said proof of concept was established in legally blind patients with RP, producing consistent, clinically meaningful visual restoration. Early data in Stargardt disease is now available, and GA is the next condition being targeted.

Because GA and Stargardt disease can leave peripheral vision intact, Monés said one open question was whether introducing light sensitivity in new retinal areas could cause visual confusion nearby. He said this does not appear to be the case in patients with Stargardt disease and will be tested formally in the GA trial.

Trial design and patient selection

The trial will initially focus on advanced GA cases, patients who are not candidates for most existing trials because their disease involves the fovea, and for whom, Monés said, “the only hope they may have is a therapy like this.” As confidence builds from later-stage disease, Monés said the plan is to move toward patients with better baseline vision, excluding those with only mild visual loss around 20/32 but potentially including patients with significant central scotoma or vision in the 20/50 to 20/60 range.

On mechanism, Monés said the therapy bypasses the photoreceptor, the cell that normally converts light into electrical signals, by introducing opsins into bipolar cells instead. Bipolar cells do not naturally detect light but can transmit electrical signals; once transfected, they become light-sensitive and pass signals to ganglion cells and the brain. Because this approach bypasses the photoreceptor and retinal pigment epithelium layer, Monés said it can theoretically apply across GA, Stargardt disease, and RP regardless of the causative gene.

Monés said the primary end point will be improvement in best-corrected visual acuity. For patients with more severe vision loss, the trial may add other functional biomarkers, while patients with earlier-stage vision loss may be assessed using microperimetry. Beyond visual acuity, Monés said the trial will also track quality-of-life measures and functional improvements such as mobility and the ability to perform daily tasks.

If enrollment begins on schedule, Monés said recruitment is expected to move quickly, given the number of patients with GA with foveal involvement excluded from most existing trials. Because the therapy aims to restore vision rather than slow further loss, he said any treatment signal should be detectable sooner than the multi-year timelines required to show a difference in lesion growth with approved anti-complement therapies. “This is very ambitious,” Monés said. “We'll see if we succeed, but the chances are there.”