Researchers with Nanoscope Therapeutics Inc., a biotechnology company committed to restoring vision in blind patients in real-world settings by developing and commercializing novel gene therapies for retinal degenerative diseases, have announced the publication of a paper, “A synthetic opsin restores vision in patients with severe retinal degeneration,” in Molecular Therapy, the flagship journal of the American Society of Gene & Cell Therapy. The publication of the paper marks a major breakthrough in mutation-independent optogenetic monotherapy for patients suffering from inherited retinal diseases.
“We are excited by the therapeutic benefits seen in retinitis pigmentosa patients with progressive and permanent loss of photoreceptors and without any treatment option,” said Dr. Santosh Mahapatra, the principal investigator for the study, and Chief Medical Officer of JPM Rotary Eye Hospital (Odisha) in India. “We look forward to further advancing this technology to help those with severe vision loss due to retinal degenerative diseases.”
Inherited retinal degenerative diseases (IRDs) are the leading cause of blindness in working-age adults worldwide, and in advanced stages, cell loss makes gene editing or replacement ineffective. Optogenetics offers a therapeutic opportunity to restore vision by photosensitizing remaining retinal neurons. However, current opsins are kinetically slow, partially activated in ambient light, unresponsive to different light colors, and target low-resolution retinal cell circuits. To overcome these limitations, the Nanoscope team engineered a synthopsin made of three selectively mutated non-mammalian proteins to achieve a broadband Multi-Characteristic Opsin (MCO).
“This paper highlights the outstanding work of the Nanoscope team in developing effective optogenetic therapies for patients with some of the highest unmet needs,” said Dr. Samarendra Mohanty, the lead author of the paper and President of Nanoscope. “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.”
The engineered synthopsin was packaged into an optimized AAV2 gene therapy vector that targets human retinal bipolar cells. In an investigator-initiated, open-label study, four blind retinitis pigmentosa patients with ABCA4 variants received a single intravitreal gene therapy injection. Noninvasive imaging confirmed retinal gene expression via a fluorescent reporter protein. Patients showed improvement in visual acuity, shape discrimination, and mobility through the 52-week study period. There were no significant safety issues despite what is likely one of the most synthetic, non-mammalian proteins ever expressed in a human. This is the first report of a gene monotherapy that can restore vision in blind patients in a mutation-independent manner utilizing an optogenetics technology platform.
“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 Dr. Vinit B. Mahajan, co-corresponding author and Professor and Vice Chair for Research, Department of Ophthalmology at Stanford University. “The ability to restore vision with a single intravitreal injection marks a significant step toward developing a universal treatment for retinal degenerative diseases.”
