Restoring vision by inserting a novel protein in the eye using gene therapy
NIH-funded therapy plan on human trial.
MCO1 opsin is a newly developed light-sensing protein. It is found that when this protein is attached to retina bipolar cells using gene therapy, it restored vision in blind mice. For the development of MCO1, a Small Business Innovation Research grant was provided to Nanoscope, LLC, by the National Eye Institute, part of the National Institutes of Health. A U.S. clinical trial of the therapy is planned for later this year.
The findings of Nanoscope is published in Nature Gene Therapy. The results show that blind mice- with absolutely no light perception received treatment and regained significant retinal function and vision. In a report of the study, it was described that the mice that were treated were significantly faster in standardized visual tests, like—navigating mazes and motion change detection.
Opsin proteins are part of the signaling cascade essential for visual perception. The opsin proteins are expressed by the rod and cone photoreceptor cells in the retina; on being activated by light, the photoreceptors pulse and relay signals through other neurons of the retina and then to the neurons in the brain.
Different types of common eye diseases like age-related macular degeneration and retinitis pigmentosa damage the photoreceptors and impair vision. Even though the photoreceptor cells might not be fully functional, other retinal neurons, including the bipolar cells, remain intact. The investigator discovered a way to put some work of the damaged photoreceptors on the bipolar cells.
Samarendra Mohanty, Ph.D., founder of Nanoscope, says that the beauty of their strategy is its simplicity. Bipolar cells are located downstream from the photoreceptors, and in the retina, when the MCO1 opsin gene is added to bipolar cells with nonfunctional photoreceptors, sensitivity to light is restored.
According to researchers, the challenges to retinal regeneration could be overcome by this new strategy previously plagued by other approaches. In cases of rare diseases like the Luxurna for Leber congenital amaurosis, gene replacement therapy worked principally. Invasive surgery and wearable hardware are required for bionic eyes, like the Argus II prosthesis. To attain the signal transduction threshold, intensification of light is required for other opsin replacement therapies. The risk of further damage is involved with intense light. The therapy proposed by Nanoscope involves a one-time injection in the eye and does not involve hardware. There is no need of flashing strong light into the eye as MCO1 is sensitive to ambient light. Since the survival of a photoreceptor is not required, MCO1 therapy can treat a wider range of degenerative retinal diseases.
There was no reported issue regarding the safety of the treated mice. The treatment and the therapy showed no signs of inflammation on blood and tissue examination. There was no off-target effect due to the therapy— MCO1 opsin was expressed only on bipolar cells.
According to research, the therapy under the best scenario will help achieve 20/60 vision in the patients; however, no one is certain on how the vision that is restored will compare to normal vision.
Subrata Batabyal, Ph.D., lead author, said that to understand how vision quality is affected with signaling through bipolar cells, a clinical study will help, for instance, how the treated eyes can interpret objects that move fast. The therapy is likely to be limited to patients suffering from severe retinal diseases.
PaekGyu Lee, Ph.D., program officer, NEI, said that if this optogenetic approach proves to be effective for restoration of vision in humans, it could prove to be an alternative to approach like retinal prosthesis, which will be valuable to patients with late-stage retinitis pigmentosa.
This research describes basic findings that help us understand biology and human behavior better, which proves to be the foundation for advancing to innovative and better prevention, diagnosis, and treatment of diseases. Advances in science rely on past discoveries, as science is an incremental and unpredictable process. With the knowledge of fundamental basic research, advances in clinical science would not be possible.
The Small Business Innovation Research (SBIR) is a funding program that supports research and development based small businesses in the U.S. with potential for commercialization. The NEI SBIR program provides funds to organizations working on technologies to address problems associated with visual impairment like blinding eye diseases or working on rare health problems or ones looking into the requirements of visually impaired individuals.
Restoring vision by inserting a novel protein in the eye using gene therapy.
