A New Type of Gene Therapy Shows Promise for Treating Retinitis Pigmentosa

A gene therapy technique significantly improved vision in many retinitis pigmentosa patients who have lost nearly all sight, according to two-year results of a phase 2b/3 clinical trial presented today at the AAO meeting in Chicago.

The new therapy, called optogenetics, essentially converts cells in the retina that don’t normally sense light into light-sensing cells. Researchers believe it might also help patients with other types of retinal degeneration.

An estimated 1.5 million people worldwide have retinitis pigmentosa, a group of rare eye diseases that affect the retina. The inherited condition causes photoreceptors, the cells in the light-sensitive layer of tissue in the back of the eye that are responsible for sight, to break down over time. Vision loss begins with a deterioration of night vision and usually progresses to loss of color, side and central vision.

There is no cure or treatment to stop it from advancing in most people with the disease. A previously approved gene therapy, Luxturna (voretigene neparvovec) replaces a faulty gene with a healthy one but works only in the 0.3% to 1% of patients who have a specific gene mutation.

The experimental optogenetics therapy, by contrast, targets cells in the retina that don’t normally sense light but often survive after photoreceptors die. The one-time intravitreal injection into the eye uses a virus vector to deliver copies of light-sensing molecules to the surviving cells, which turns them into light-sensing cells to replace lost photoreceptors.

The therapy, called MCO-010, is “mutation agnostic,” meaning it doesn’t work by replacing a specific gene. Rather, it counteracts damage to the retina caused by numerous genetic mutations. Researchers believe that this strategy potentially could treat more people with degenerative retinal diseases, including macular degeneration and Stargardt disease.

For their trial, lead researcher Allen C. Ho, M.D., director of retina research and co-director of the Retina Services at Wills Eye Hospital — and chief medical advisor at Nanoscope Therapeutics, which is developing MCO-010 — and his colleagues randomized 27 patients with severe vision loss characterized as hand motion, light perception or worse into three groups: high- or low-dose treatment, or sham treatment.

Allen C. Ho, M.D.

Earlier studies showed that both MCO-010-treated groups experienced an increase in visual acuity compared with the sham treatment group at weeks 52 and 76, with no patients suffering a significant side effect.

The abstract that Ho presented at the AAO meeting showed 100-week results. Between 40% and 50% of participants in the treatment arms gained three lines of vision on an eye chart, which Ho described in a news release

“We are finally on the brink of an impactful therapy for people with severe vision loss,” Ho said. "These findings finally deliver hope to patients and ophthalmologists that something is close to being able to help them.”

Nanoscope Therapeutics plans to initiate a biologics license application submission to the FDA early next year, according to the news release. The agency has already granted it fast track designation.

Ho said that Nanoscope has also begun start-up activities for a phase 3 trial evaluating MCO-010 for Stargardt macular degeneration.