Researchers with Nanoscope Therapeutics announced the publication of a paper, “A synthetic opsin restores vision in patients with severe retinal degeneration,” in Molecular Therapy. Its publication marks a step forward in mutation-independent optogenetic monotherapy for patients suffering from inherited retinal diseases, the company said in a press release.
According to Nanoscope, while optogenetics offers a therapeutic opportunity to restore vision by photosensitizing remaining retinal neurons, 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 3 selectively mutated non-mammalian proteins to achieve a broadband Multi-Characteristic Opsin.
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, 4 blind retinitis pigmentosa (RP) 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, according to Nanoscope Therapeutics. 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, the company said.
“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.”