Optogenetic Therapy Shows Efficacy in Autosomal Recessive Retinitis Pigmentosa

Results from a phase 1/2 study from Nanoscope Therapeutics were presented at the 2021 ASRS meeting.

Nanoscope Therapeutics presented positive data from their phase 1/2 study (NCT04919473) of MCO-010 in patients with retinitis pigmentosa (RP) at the 2021 Annual Meeting of the American Society of Retina Specialists (ASRS), October 8-12.1,2

The presentation was given by Sai H. Chavala, MD, professor, Texas Christian University and University of North Texas Health Science Center School of Medicine. The study evaluated the multi-characteristic opsin (MCO) therapy’s effect on ON-bipolar cells in patients with RP and ABCA4 mutations.

“Optogenetics offers the potential for vision restoration in RP by photosensitizing higher order bipolar neurons. It is ‘gene-agnostic’, focusing on disease phenotype in a mutation independent manner, and applicable to a wide population of patients with retinal degenerations. This therapy differs by not requiring an external device for stimulation,” Chavala said in his presentation.2

In the study, 4 participants with severe RP received a single intravitreal injection of MCO-010. The therapy consists of MCO-encoded genes delivered by adeno-associated virus vector 2 (AAV2) which reprograms ON-bipolar neurons to be activated by ambient light.

READ MORE: Gene Therapy for Retinal and Neurological Diseases

Investigators found that visual acuity improved from a mean of 1.95 logMAR at baseline to 1.46 logMAR at 52 weeks post-treatment. Additional improvements were also seen in mobility score, shape discrimination accuracy, and visual field at a dose of 3.5 x 1011 vg per eye. Patient-reported outcomes supported the therapy’s efficacy, as patient scores improved on the Visual Function Questionnaire.

“We have very promising data in our phase 1/2 study in patients with retinitis pigmentosa... with a single intravitreal injection, in 2 different doses and groups, we see improvements in activities of daily living measured by visual function and mobility tests we did. The high dose group, especially, improved in visual equity tremendously,” Samarendra Mohanty, PhD, founder and president, Nanoscope Therapeutics, previously told GeneTherapyLive.

In terms of safety, the therapy was well-tolerated and no serious adverse events (AEs) were reported. There were mild –to moderate increases in intraocular pressure (IOP), but these resolved with topical IOP-lowering medications without sequelae. Similarly, mild self-limited ocular inflammation was observed and subsequently controlled with topical steroids. At the end of the study, no patient required medications for AEs.

Chavala concluded that MCO-010 had a positive trend in visual improvements for patients with RP regardless of underlying gene mutations. Therefore, this proof-of-concept study provides a rationale for further investigation of the therapy for both RP and other inherited retinal degenerative diseases.

A randomized, double-blind, multi-center phase 2b trial (NCT04945772) assessing MCO-010 is currently recruiting. Results are expected in the fourth quarter of 2022. MCO-010 previously received orphan drug designations from the FDA for RP and Stargardt disease.

“In our next trial, we are combining different cone-rod dystrophies: choroideremia, Leber congenital amaurosis, and Stargardt disease, in 1 trial. That's the second trial we’re planning in our pipeline that will be with a viral vector delivery. Also, we are advancing the non-viral delivery method of nano-enhanced optical delivery for geographic atrophy in dry AMD or wet AMD,” Mohanty previously told GeneTherapyLive.

REFERENCES
1. Positive data from Nanoscope's phase 1/2a trial of gene therapy to restore vision in patients blinded by retinitis pigmentosa to be featured at 2021 ASRS meeting. News release. Nanoscope Therapeutics. October 8, 2021. https://starlocalmedia.com/news/state/positive-data-from-nanoscopes-phase-1-2a-trial-of-gene-therapy-to-restore-vision-in/article_933f549d-e74a-5d85-aee4-14ef18f76ec6.html
2. Chavala SH, Singer MA, Mahapatra S, et al. Intravitreal AAV2 Optogenetic Vision Restoration in retinal degenerative patients with ABCA4 mutation. Presented at ASRS 2021 Annual Meeting. October 8-12, 2021. San Antonio, TX.