A Gene Therapy Aims to Do What Dry Macular Degeneration Drugs Cannot: Restore Sight

A Gene Therapy Aims to Do What Dry Macular Degeneration Drugs Cannot: Restore Sight

Early results from a one-time eye injection that turns surviving retinal cells into light sensors are paving the way for a trial in geographic atrophy, a leading cause of blindness in older adults. The 2026 Nobel Prize in Physiology or Medicine was this week awarded to three researchers whose discoveries are the basis of this experimental therapy.<_o3a_p>

NEW ORLEANS - For the roughly one million Americans living with geographic atrophy, the advanced form of dry age-related macular degeneration, the best medicine can currently offer is time. Two drugs approved by the Food and Drug Administration can slow the steady erosion of central vision, but neither can give back what has already been lost. <_o3a_p>

A study presented this week at the 130th annual meeting of the American Academy of Ophthalmology suggests that may one day change. Researchers reported that a single injection of an experimental gene therapy, sonpiretigene isteparvovec, known as son-vec, improved vision in patients with a related inherited form of macular disease, and produced encouraging signals in an animal model of geographic atrophy. The findings were strong enough, the team said, to justify moving directly into a randomized controlled Phase 2 trial in patients with dry macular degeneration, bypassing the usual first-stage safety study.<_o3a_p>

"There are currently FDA-approved treatments to slow down geographic atrophy progression, but no treatments are currently available to improve vision," said David S. Boyer, MD, a world-renowned ophthalmologist and the study's lead researcher. "Having a one-time injection, which appears safe, that may improve vision for my patients was a great reason to do the study."<_o3a_p>

Rewiring the Retina<_o3a_p>

Macular degeneration destroys photoreceptors, the rods and cones at the back of the eye that convert light into the electrical signals the brain reads as images. Once those cells die, conventional treatments have little to work with.<_o3a_p>

Son-vec takes a different approach, drawing on a field known as optogenetics. Optogenetics is the exciting new research field recognized this week with a Nobel Prize. Rather than trying to save or replace photoreceptors, the therapy delivers a gene to bipolar cells, a layer of retinal neurons that normally relay signals from the photoreceptors and often survive after the photoreceptors are gone. Once the gene is in place, those bipolar cells produce a light-sensitive protein called an opsin, allowing them to respond to light directly. In effect, the therapy recruits a surviving part of the retina to take over the job of the cells that have been lost.<_o3a_p>

The treatment is given as an intravitreal injection, a routine procedure in retina clinics.<_o3a_p>

Promising Early Data<_o3a_p>

The results presented at the meeting came from two complementary lines of research.<_o3a_p>

In an open-label Phase 2 trial conducted at multiple centers, patients with Stargardt disease, an inherited condition that causes macular damage resembling that of geographic atrophy, received a single injection of son-vec. All had vision of 20/200 or worse, the threshold for legal blindness in the United States. Among patients whose atrophy was confined to the macula, vision improved by an average of 12 letters on a standard eye chart, a gain of more than two lines. The treatment was well tolerated, and no serious adverse events were reported.<_o3a_p>

In parallel, a dose-ranging study in nonhuman primates with laser-induced damage designed to mimic geographic atrophy showed that the therapy's protein was produced in retinal neurons, and that treated eyes generated significantly stronger electrical responses on multifocal electroretinography, a test that measures how different areas of the retina respond to light.<_o3a_p>

The therapy has also been tested in patients with retinitis pigmentosa, another inherited disease that destroys photoreceptors, with improvements in some aspects of visual function.<_o3a_p>

A Surprise for the Researchers<_o3a_p>

Dr. Boyer said the results were not what he had braced for. His concern going in was that in eyes where some healthy cells remained, those cells might also be affected by the therapy, making any improvement in vision difficult to detect.<_o3a_p>

"Yes, I was surprised," he said. "I was concerned that the viable cells would be upregulated and the visual improvement would be masked, and it wasn't."<_o3a_p>

What Comes Next<_o3a_p>

The researchers caution that the human data so far come from patients with Stargardt disease, not age-related macular degeneration, and that the trial was open-label, meaning patients and doctors knew who received treatment. The randomized trial now planned in geographic atrophy is designed to test whether the benefit holds up in the far larger population of older adults with the disease.<_o3a_p>

Beyond that, Dr. Boyer said, the goal is to "do Phase 2b/3a trials to confirm these early results and to obtain FDA approval."<_o3a_p>

For ophthalmologists, he said, the message is one of cautious hope: "There may be a treatment for patients with visual loss secondary to geographic atrophy in the future that hopefully will result in visual gains."<_o3a_p>

And for patients and their families, he pointed to a broader shift in the field. "This and other companies are exploring better and earlier ways to treat dry AMD," he said.<_o3a_p>

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About the American Academy of Ophthalmology
The American Academy of Ophthalmology is the world's largest association of eye physicians and surgeons. A global community of 32,000 medical doctors, we protect sight and empower lives by setting the standards for ophthalmic education and advocating for our patients and the public. We innovate and support research to advance our profession and to ensure the delivery of the highest-quality eye care. Our EyeSmart® program provides the public with the most trusted information about eye health. For more information, visit aao.org.
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