AAO 2026: Optogenetic gene therapy heads to phase 2 trial in geographic atrophy

The two US Food and Drug Administration (FDA)-approved therapies for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) slow lesion growth but do not recover lost vision. Data presented at the 130th Annual Meeting of the American Academy of Ophthalmology (AAO) in New Orleans from October 9-12, 2026, suggest that an optogenetic gene therapy may eventually address that gap.¹

Investigators reported that a single intravitreal injection of sonpiretigene isteparvovec (son-vec; formerly MCO-010; Nanoscope Therapeutics) was associated with acuity gains in patients with Stargardt disease and with stronger retinal electrical responses in a nonhuman primate model of GA.¹ Based on these findings, the team plans to proceed directly to a randomized, controlled phase 2 trial in patients with GA, without a separate phase 1 safety study in that population.¹

"No treatments are currently available to improve vision," said David S. Boyer, MD, the study's lead investigator, referring to patients with GA.¹

Study overview

The presentation highlights 2 lines of research.¹ The first: an open-label, multicenter phase 2 study in which patients with Stargardt disease and visual acuity of 20/200 or worse each received a single injection of son-vec. According to the data, patients whose atrophy was limited to the macula gained an average of 12 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. The therapy was well tolerated, with no serious adverse events (AEs) reported.¹

These results add to the published STARLIGHT trial (NCT05417126), an open-label phase 2 study of 6 adults with Stargardt disease treated at 1.2 × 10¹¹ vector genomes per eye in the worse-seeing eye.^2,3 In that cohort, mean best-corrected visual acuity (BCVA) improved by 5.5 letters from baseline at 48 weeks (SD, 12.29). Acuity measured with a wearable magnifier improved by 13.3 letters (SD, 21.37).² The investigators reported no deaths, hospitalizations, retinal detachments, or endophthalmitis. The most common adverse events were conjunctival hemorrhage, ocular hypertension, and vitreous cells.²

The second line of research was a dose-ranging study in nonhuman primates with laser-induced lesions designed to model GA. Treated eyes expressed the opsin in retinal neurons and produced significantly stronger responses on multifocal electroretinography than untreated eyes.¹ These preclinical data have not yet been published in a peer-reviewed journal.

Clinical context

GA is estimated to affect around 1 million people in the United States, with AMD remaining a leading cause of irreversible vision loss among older adults.^1,4

In 2023, the FDA approved 2 complement inhibitors for GA: pegcetacoplan injection (Syfovre; Apellis Pharmaceuticals) and avacincaptad pegol intravitreal solution (Izervay; Astellas). Both are indicated to slow the progression of GA lesions. Neither has been shown to improve visual acuity.^5,6 And no approved therapy currently restores function to the retina, where photoreceptors have already been lost.

Mechanism and development history

Rather than using gene replacement, son-vec uses optogenetics. Through this treatment approach, an adeno-associated viral vector delivers a gene encoding a multi-characteristic opsin to ON bipolar cells, which often survive after photoreceptors degenerate; and the bipolar cells then respond directly to light.^1,7 Because this approach does not target a specific causative mutation, it is described as mutation agnostic. The injection is given intravitreally in the office.

The underlying field was recognized this week when the 2026 Nobel Prize in Physiology or Medicine went to Karl Deisseroth, MD, PhD; Peter Hegemann, PhD; and Georg Nagel, PhD, for discoveries that made optogenetics possible.⁸

Son-vec is furthest along in retinitis pigmentosa (RP). Its pivotal program was the phase 2b RESTORE trial (NCT04945772), a randomized, double-masked, sham-controlled study of 27 patients.⁹

In September 2026, the FDA accepted a Biologics License Application (BLA) for son-vec under the proposed brand name Mogenry for adults with RP and severe vision loss.⁷ The therapy also holds orphan drug and Regenerative Medicine Advanced Therapy (RMAT) designations for Stargardt disease.⁷

Interpretation

The Stargardt findings point to a possible role in diseases where macular atrophy dominates. Several factors argue for caution in applying them to GA. The human data so far come from small, open-label cohorts with an inherited disease, not from older adults with AMD.

Boyer said he had expected that the therapy's effect on remaining viable cells might obscure any acuity benefit, and that this did not happen.¹ Whether that holds in eyes with GA—which typically retain more functioning photoreceptors at the lesion margins—is still unknown.

Limitations and next steps

The 12-letter mean gain cited for the macula-confined Stargardt subgroup comes from conference data. The release does not report the subgroup size or follow-up duration, and the figure has not yet been published.¹ Both Stargardt studies were open-label, without masking or sham control. The GA evidence is limited to an animal model.

The investigators say the planned randomized phase 2 trial in GA is intended to test whether the benefit carries over to that larger population. If the results are positive, they plan phase 2b/3a trials aimed at regulatory approval.¹ As of publication, no registry record for the GA trial could be identified.

REFERENCES

1. American Academy of Ophthalmology. A gene therapy aims to do what dry macular degeneration drugs cannot: restore sight. News release. October 6, 2026. https://www.aao.org/newsroom/news-releases/detail/gene-therapy-aims-to-restore-sight

2. Lam BL, Zak V, Gonzalez VH, et al. Safety and efficacy of MCO-010 optogenetic therapy in patients with Stargardt disease in USA (STARLIGHT): an open-label multi-center Ph2 trial. EClinicalMedicine. 2025;87:103430. doi:10.1016/j.eclinm.2025.103430. https://doi.org/10.1016/j.eclinm.2025.103430

3. Nanoscope Therapeutics. Safety and efficacy of MCO-010 in patients with Stargardt disease (STARLIGHT). ClinicalTrials.gov identifier: NCT05417126. https://clinicaltrials.gov/study/NCT05417126

4. Friedman DS, O'Colmain BJ, Muñoz B, et al; Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122(4):564-572. doi:10.1001/archopht.122.4.564. https://doi.org/10.1001/archopht.122.4.564

5. US Food and Drug Administration. Drugs@FDA: Syfovre (pegcetacoplan injection), NDA 217171. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=217171

6. US Food and Drug Administration. Drugs@FDA: Izervay (avacincaptad pegol intravitreal solution), NDA 217225. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=217225

7. FDA accepts BLA for Mogenry in retinitis pigmentosa. Ophthalmology Times. September 2026. https://www.ophthalmologytimes.com/view/fda-accepts-bla-for-mogenry-in-retinitis-pigmentosa

8. 2026 Nobel Prize in Medicine awarded for brain research tool called optogenetics. STAT. October 5, 2026. https://www.statnews.com/2026/10/05/nobel-prize-medicine-2026-winner-deisseroth-hegemann-nagel/

9. Nanoscope Therapeutics. Efficacy and safety of MCO-010 optogenetic therapy in adults with retinitis pigmentosa (RESTORE). ClinicalTrials.gov identifier: NCT04945772. https://clinicaltrials.gov/study/NCT04945772