Retinal Degenerations: New Clinical Trials for Retinal Degenerative Diseases

Retinitis pigmentosa, Stargardt disease, and atrophic maculopathy are retinal disorders with different causes but a common feature: progressive degeneration of the retina, photoreceptor loss, and severe impairment of visual function.

Photoreceptors are the only nerve cells capable of responding to light stimuli by generating electrical impulses that initiate the visual process. These nerve impulses are transmitted to adjacent bipolar cells, then to ganglion cells, the optic nerve, and finally to the visual cortex, where they are processed and perceived as images.

As photoreceptors degenerate, visual function progressively declines, and in advanced stages, patients experience low vision or blindness. Research aimed at developing effective therapeutic options for retinal degenerations focuses on either preventing photoreceptor loss or restoring visual function in patients who have already lost these cells.

Among the therapeutic approaches following the second path, one particularly promising strategy is based on the use of Multi-Characteristic Opsins (MCOs)—lab-engineered proteins capable of making ON bipolar cells responsive to light, effectively replacing the lost photoreceptors.

The use of opsins to restore vision is part of a next-generation platform called optogenetics, which combines biotechnology, molecular genetics, gene therapy, and pharmacosurgery. The U.S.-based biotech company Nanoscope Therapeutics has developed a high-performance multi-characteristic opsin called MCO-010, tested in multiple clinical trials involving patients with retinitis pigmentosa and Stargardt disease.

Therapy with MCO-010 involves the creation of therapeutic DNA encoding the opsin, packaging the DNA molecules into proprietary AAV2 viral vectors, and delivering them into the patient’s eye via a single intravitreal injection.

Once inside the eye, the viral vectors reach the bipolar cells and release the therapeutic DNA, enabling the cells to produce multiple copies of MCO-010. The opsins then localize to the surface of the bipolar cells, making them capable of detecting light and generating a nerve signal, which is transmitted to the ganglion cells, optic nerve, and eventually the brain, in a way very similar to the natural visual process.

Nanoscope Therapeutics has conducted several clinical trials for MCO-010:

RESTORE (Phase II/III) for retinitis pigmentosa, and
STARLIGHT (Phase II) for Stargardt disease.

The company presented early results from both studies at the American Academy of Ophthalmology (AAO) Annual Meeting held last October in Chicago.

Both trials demonstrated significant improvements in visual function and high safety of the therapy in treated patients. These encouraging results have paved the way for Phase IV trials in retinitis pigmentosa and Phase III trials in Stargardt disease.

Nanoscope Therapeutics has also developed a next-generation opsin, MCO-020, designed to restore vision in patients with advanced atrophic maculopathy in the geographic atrophy stage. Unlike previous versions, MCO-020 is administered via an innovative delivery system that does not require viral vectors. The first Phase I/II clinical trial for MCO-020 is expected to begin by the end of this year.

At present, multi-characteristic opsin-based experimental therapy is the only therapeutic platform with the potential to restore light sensitivity in patients affected by various types of retinal diseases. It enables real-time visual processing under natural lighting conditions.

Based on the results of completed and ongoing clinical trials, optogenetic therapy with MCOs could become the first agnostic therapy approved for multiple retinal degenerations, regardless of their underlying cause—offering real hope of treatment for millions of patients worldwide.

For this reason, the progress of Nanoscope Therapeutics’ research is drawing strong media attention, and we believe it is important to explain its meaning and potential to patients with retinal diseases, their families, general practitioners, medical students, and anyone interested in this field.