Nanoscope Therapeutics publishes clinical results of MCO-010 findings for patients with retinitis pigmentosa
The synthetic opsin was packaged into an optimised AAV2 gene therapy vector that targets human retinal bipolar cells.
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Nanoscope Therapeutics announced1 the publication of clinical data on vision restoration in retinitis pigmentosa (RP) in a paper titled “A synthetic opsin restores vision in patients with severe retinal degeneration," which appeared in Molecular Therapy.
In the paper,2 investigators described Multi-Characteristic Opsin (MCO-010), a synthetic opsin with broad spectral sensitivity. Administered via intravitreal injection, Synthopsin-MCO-010 possesses a promoter to specifically target ON-bipolar cells. According to the authors, in preclinical trials, Synthopsin-MCO-010 was shown to restore the visual behavior in RP mouse models. For the study, the synthopsin was packaged into an optimised AAV2 gene therapy vector that targets human retinal bipolar cells.
For the study, four RP patients with ABCA4 variants were enrolled. Of those enrolled, three were male and one was female, with an average of 45.5 years of age. Patients had severe vision loss before treatment and were “unable to move around without the help of another person,” per the authors. All patients were legally blind with hand-motion to light-perception vision.
Subjects received 10 days of prophylactic oral steroids to mitigate any host immune response to AAV2 beginning 3 days prior to treatment and followed with a taper regimen. Each patient then received a single intravitreal injection of 100 µl AAV2-MCO-010 (vMCO-010) in the eye with worse visual acuity and underwent vision and visual function testing for 52 weeks.
Freiburg Visual Acuity Testing (FrACT) was used to quantify the best corrected visual acuity (BCVA) in logMAR units. According to the paper, all 4 patients showed improvement (lower logMAR) at week 12 and an overall average BCVA improvement at weeks 12 and 16.
One patient developed inflammatory keratic precipitates (KP) that led to fluctuations in BCVA between weeks 4-16. BCVA was improved after KP was resolved with topical steroid drops.
Furthermore, it was noted that overall statistical significance was lost at 31 and 52 weeks. In the paper, it is stated that this was due to either “the better-improved patient dropping out after 16 weeks due to the COVID-19 lockdown," and in the case of another patient, they "had decreased VA at 31 and 52 weeks, attributed to the development of vitreous haze.”
It was also noted that mean visual field index (VFI) increased following vMCO-010 injection. One patient did have decreased VFI at week 4 due to KP, but VFI increased from 8 to 52 weeks. Two patients did not show increased VFI, but BCVA did improve. It was noted in the paper that “the variability in BCVA and VFI may be due in part to the variable expression of MCO-010 in the central macula compared to the peripheral retina.”
Overall, MCO-010 demonstrated statistically significant improvement (>0.3 logMAR) in visual acuity, and some subjects demonstrated improved visual fields. No serious adverse events or suspected unexpected serious adverse reactions to the treatment were reported.
Samarendra Mohanty, PhD, lead author of the paper and President of Nanoscope commented on the paper in a press release from Nanoscope stating, “This paper highlights the outstanding work of the Nanoscope team in developing effective optogenetic therapies for patients with some of the highest unmet needs. The positive results of our Phase 1/2a trial outlined in this journal article, along with the randomised controlled trial data in RP, represent a major step forward in treating inherited retinal diseases.”
Vinit B. Mahajan, MD, PhD, co-corresponding author and professor and vice chair for research, department of ophthalmology at Stanford University, commented on the study in a press release from Nanoscope.
“Our study represents a pivotal milestone in the treatment of inherited retinal degenerations, demonstrating that optogenetics can successfully restore vision in blind patients, regardless of their genetic mutation,” said Mahajan. “The ability to restore vision with a single intravitreal injection marks a significant step toward developing a universal treatment for retinal degenerative diseases.”
References:
Nanoscope announces publication of clinical data on vision restoration in retinitis pigmentosa. Published March 24, 2025. Accessed March 25, 2025. https://nanostherapeutics.com/2025/03/24/nanoscope-announces-publication-of-clinical-data-on-vision-restoration-in-retinitis-pigmentosa/
Mohanty SK, Mahapatra S, Batabyal S, Carlson M, Kanungo G, Ayyagari A, Tchedre K, Franco JA, Singer M, Barone S, Chavala S, Mahajan VB, A synthetic opsin restores vision in patients with severe retinal degeneration, Molecular Therapy (2025), doi: https://doi.org/10.1016/ j.ymthe.2025.03.031.
