New research opens up gene therapy for a wider range of degenerative retinal diseases

By Rachel Arthur

- Last updated on GMT


Related tags Gene therapy degenerative diseases

Scientists have used gene therapy and a newly developed light-sensing protein to restore sight in mice: with the technology to start clinical trials in the US later this year.

Research published in Nature Gene Therapy​ today shows how the light-sensing protein (MCO1 opsin) can restore vision in blind mice when attached to retina bipolar cells using gene therapy.

Nanoscope LLC received a Small Business Innovation Research grant from the US National Eye Institute (part of the National Institutes of Health) to develop MC01.

The research opens up the field for gene therapy for a number of degenerative retinal diseases where photoreceptors are damaged.

AAV2 assisted delivery 

Opsins are proteins that signal other cells as part of a series of signals needed for sight. In a normal eye, opsins are expressed by the rod and cone photoreceptors in the retina.

A number of common eye diseases - including age-related macular degeneration and retinitis pigmentosa - damage the photoreceptors.

But while the photoreceptors may no longer fully function, other retinal neurons, including bipolar cells, remain intact. The researchers have found a way for bipolar cells to take on some of the work of damaged photoreceptors.

Biopolar cells are downstream from photoreceptors, so when the MC01 opsin gene is added to these biopolar cells, light sensitivity can be restored.

The researchers used AAV2 assisted delivery of highly photosensitive multi-characteristic opsin (MC01) onto ON-bipolar cells of mice with retinal degradation to allow activiation by ambient light.

Researchers explored the delivery efficacy by using different doses of AAV2 carrying MCO1 (vMCO1) into targeted cells and analysed the results over the 6 months after delivery. They found that treated mice were able to perform significantly faster in standardized visual tests, such as navigating mazes and detecting changes in motion.

New area of treatment for damaged photoreceptor diseases

To date, gene replacement therapy has worked mainly in diseases that leave photoreceptors intact (such as Luxturna for Leber congenital amaurosis).

The new research means that therapy with MC01 could be investigated for a wider range of degenerative retinal diseases, without requiring photoreceptors to survive.

It could also offer a better option that other solutions: bionic eyes require invasive surgery and wearable hardware; while other opsin replacement therapies require intense light to be strong enough to create a signal (with intense light risking further retina damage).

Researchers suggest that, in a best-case scenario, the therapy could help patients achieve 20/60 vision. It is likely to be limited to patients with severe retinal disease: and further research will explore how bipolar cells can be used.

Subrata Batabyal, Ph.D., lead author of the study, said: "A clinical study in people will help us understand how signaling through bipolar cells affects vision quality; for example, how well treated eyes can pick out fast-moving objects."

Source: Batabyal, S., Gajjeraman, S., Pradhan, S. et al.​ Sensitization of ON-bipolar cells with ambient light activatable multi-characteristic opsin rescues vision in mice. Gene Therapy​ (October 22, 2020).

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