Nanoscope Therapeutics’ Gene Therapy MCO-010 Restores Vision in Patients With Retinitis Pigmentosa
At 12 weeks posttreatment, all 4 of the patients showed improvement in the form of a lower logMAR.
This article originally appeared on our sister site, Ophthalmology Times Europe®.
Nanoscope Therapeutics’ MCO-010 (sonpiretigene isteparvovec), an investigational ambient-light activatable multi-characteristic opsin (MCO) gene therapy, showed the ability to restore vision in patients with retinitis pigmentosa (RP) in clinical data published Molecular Therapy.1
In the paper, which is entitled “A synthetic opsin restores vision in patients with severe retinal degeneration," MCO-010 was described. A synthetic opsin with broad spectral sensitivity administered via intravitreal injection, Synthopsin-MCO-010 includes a promoter to specifically target ON-bipolar cells. In preclinical research, Synthopsin-MCO-010 demonstrated the ability to restore the visual behavior in RP mouse models, according to the authors. In the in-human study, the synthopsin was packaged into an optimised AAV2 gene therapy vector targeted at human retinal bipolar cells.
Four patients with RP with ABCA4 variants were enrolled in the study. The group included 3 male patients and 1 female patient, and the average age of the participants was 45.5 years. According to the authors, the participants had severe vision loss prior to treatment and were “unable to move around without the help of another person." Furthermore, all of the participants were considered legally blind and had hand-motion to light-perception vision.
Starting 3 days before administration of the gene therapy, all patients were given 10 days of prophylactic oral steroids with the intention of mitigating immune responses, followed with a taper regimen. AAV2-MCO-010 (vMCO-010) was administered via a single intravitreal injection at a dose of 100 µl in the eye with worse visual acuity in each patient. Patients were tested for vision and visual function during the 52 weeks after receiving the gene therapy administration.
Best corrected visual acuity (BCVA) was quantified with Freiburg Visual Acuity Testing (FrACT) in logMAR units. At 12 weeks posttreatment, all 4 of the patients showed improvement in the form of a lower logMAR, according to the paper. At 12 and 16 weeks posttreatment, an overall average BCVA improvement was also observed.
It was noted that inflammatory keratic precipitates (KP) led to fluctuations in BCVA between weeks 4 to 16 in 1 patient. The patient's BCVA improved following resolution of the KP via the use of 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 stated 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 patients demonstrated improved visual fields. No serious adverse events or suspected unexpected serious adverse reactions to the treatment were reported.
“This paper highlights the outstanding work of the Nanoscope team in developing effective optogenetic therapies for patients with some of the highest unmet needs," lead author Samarendra Mohanty, PhD, the president of Nanoscope, said in a Nanoscope press release. "The positive results of our phase 1/2a trial outlined in this journal article, along with the randomized controlled trial data in RP, represent a major step forward in treating inherited retinal diseases.”
“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,” cocorresponding author Vinit B. Mahajan, MD, PhD, professor and vice chair for research in the department of ophthalmology at Stanford University, added to the statement. “The ability to restore vision with a single intravitreal injection marks a significant step toward developing a universal treatment for retinal degenerative diseases.”
