MCO-010 at 3 years: gene-agnostic gains in retinitis pigmentosa

Gene replacement therapy for retinitis pigmentosa (RP) reaches only a single genetic subtype: voretigene neparvovec (Luxturna; Spark Therapeutics) is approved for confirmed biallelic RPE65 mutation–associated retinal dystrophy and requires viable retinal cells. For the far larger group of patients whose photoreceptors are already lost, no approved therapy restores vision, and management has largely been limited to low-vision support and disease monitoring. Optogenetics takes a different route, conferring light sensitivity on surviving inner retinal neurons rather than repairing the defective gene.

At the 2026 American Society of Retina Specialists (ASRS) annual meeting, Modern Retina spoke with Benjamin Bakall, MD, PhD, director of clinical research at Associated Retina Consultants and clinical assistant professor at the University of Arizona College of Medicine–Phoenix. Bakall presented 3-year follow-up data on MCO-010 (sonpiretigene isteparvovec; Nanoscope Therapeutics).

As previously reported in Modern Retina, REMAIN follow-up of the phase 2b/3 RESTORE trial (NCT04945772) showed that a single intravitreal injection of MCO-010 produced durable best-corrected visual acuity (BCVA) improvements of approximately 3 ETDRS lines through week 152 in patients with severe vision loss from RP.¹ At the week-76 key secondary end point, the high dose produced a mean BCVA gain of 0.539 LogMAR versus sham (P = .001).² Across the 27-patient cohort, mutation type did not correlate with outcome, while better baseline BCVA and greater MCO-010 expression on fundus autofluorescence imaging did. The therapy was well tolerated, with no treatment-related serious adverse events, and a biologics license application is underway.

In the following Q&A, Bakall discusses bipolar cell targeting, the durability of the acuity gains, the baseline factors that predicted a stronger response, and how to frame optogenetic therapy for patients without overpromising.

Transcript lightly edited for length and clarity.

>> Click here to watch the video interview with Bakall from ASRS 2026.

Modern Retina: How does MCO-010 restore vision when photoreceptors are already gone? What changes in vision were observed in treated patients at 3 years?

Benjamin Bakall, MD, PhD: In patients with advanced retinal dystrophies, including retinitis pigmentosa, we know that the photoreceptors are gone. Patients have lost them, and they have severe vision loss. But oftentimes there are cells remaining in the retina, especially the bipolar cells, and those are targeted with this multi-characteristic opsin using an AAV vector, with a single intravitreal injection, for a more durable improvement in vision long term.

In the RESTORE study, at the 1-year primary end point, we could see that there was a clinically and statistically significant improvement in visual acuity using the Freiburg visual acuity chart of 3 lines in both of the doses we used, compared with sham. And in the 3-year data in the REMAIN study, we could see durability of that 3-line gain in vision in both of the treatment doses, which is really exciting.

Modern Retina: MCO-010 is described as disease-agnostic. Did the underlying genetic mutation affect the outcome? What baseline characteristics appeared to predict a stronger response and what did the safety profile look like?

Bakall: In these 27 patients, there were 15 different gene mutations, and several were undetermined mutations. We really did not see that the mutations had a specific effect on the outcome or on the improvement in vision. So this is truly a gene-agnostic treatment for advanced retinal dystrophy and retinitis pigmentosa.

We looked specifically at 2 different outcomes: the patients who improved 6 lines or better in visual acuity, and patients who had improvement in 2 of the 3 outcomes, which were visual acuity, multi-luminance mobility testing (MLMT) and multi-luminance shape discrimination testing (MLSDT). In those 2 main outcomes, we could see that the patients who had less thinning of the retina and better vision at baseline did better.

Regarding safety, anytime we do intravitreal injections we are always worried about safety, and inflammation is a key part of that. Fortunately, in this study we only saw mild or moderate levels of inflammation that could be treated. And we did not see any evidence of occlusive vasculitis, hypopyon, hypotony or retinitis, which is really important. Fitting this into the broader landscape, we think this is a relatively safe treatment, and it seems to be durable at 3 years.

Modern Retina: For patients who have been told nothing can be done, how should a therapy like this be discussed without overpromising?

Bakall: For patients who have advanced retinal dystrophy and retinitis pigmentosa, we do not want to overpromise. We want them to be realistic about this treatment. But what is really exciting are the patient-reported outcomes. Some of the patients in this study reported that they are able to ambulate better and see things in their surroundings better. Sitting down at the table, they can see the utensils and the plate and see what they are eating much better. Some patients also reported that when they are passengers in a car, they can now see other cars moving around.

Those patient-reported outcomes are really key to showing that there is true clinical benefit with this treatment long term, and discussing other patients' experiences with a patient can help. That is why I am an inherited retina specialist. I am in this area to be able to find new treatments that can help my patients, because realistically, right now there is no other treatment that is effective for patients with advanced retinal dystrophy and retinitis pigmentosa.

Modern Retina: Where is vision restoration for advanced retinal disease headed over the next 5 years?

Bakall: Talking about this area of treatment, optogenetics, and specifically multi-characteristic opsin, the first step is hopefully having approval of this treatment for retinitis pigmentosa. But in the pipeline, maybe also the same treatment for Stargardt disease, and maybe in the future advanced age-related macular degeneration. I am also very hopeful about other treatments. Comparing with 10 years ago, when we only had one active trial for inherited retinal disease, now I think there are more than 60 different trials across different retinal dystrophies. That is really exciting. We may have more treatments coming out soon.