Children with a rare form of eye disorder who were born blind can now see thanks to a “remarkable” gene therapy breakthrough.
Researchers from London’s Moorfields Eye Hospital, biotech firm MeiraGTx and University College London have demonstrated that their therapy is both safe and effective in improving the vision of and slowing retinal deterioration in young patients born with “LCA-AIPL1.”
This previously untreatable genetic disorder, which affects some 2–3 of every 10 million newborns, leads to profound visual impairments and legal blindness.
In turn, this causes affected children to typically experience delayed and disrupted development in areas such as behavior, communication and mobility.
After trials of the new procedure, however, children that before could only play with toys by feeling are now able to safely run about, identify pictures and even drive go-karts.
“It’s an absolutely transformational improvement,” paper author and Moorfields ophthalmologist Michel Michaelides told Newsweek.
LCA (Leber congenital amaurosis) is the name given to a family of inherited eye disorders that affect the retina—the layer at the back of the eyeball containing light-sensitive “photoreceptor” cells.
These disorders are seen in roughly 2–3 out of every 100,000 births. There are many types of LCA and these vary depending on which of the genes involved in the development and function of the retina are affected.
At present, the only treatable form of LCA is that which involves a mutation in the gene coding for RPE65, a protein involved in the “visual cycle” that translates photons of light into electrical signals that the brain can then interpret.
Specifically, the protein helps refresh special pigments in photoreceptor cells so that they can be used over again. Without it, vision cannot be sustained.
Children with LCA-RPE65 tend to have poor night vision from birth and reduced day vision.
“They will recognize spaces and colors, and they’ll be on the vision chart,” Michaelides explains.
In 2017, the U.S. Food and Drug Administration (FDA) approved Luxturna, a gene therapy, for the treatment of RPE65-associated LCA. Gene therapies work by using a virus to install a new, healthy copy of a faulty gene into a patient’s cells to help address the underlying problem.
RPE65 mutations, however, only underlie about eight percent of LCA cases—and such are on the relatively milder end of the spectrum, in terms of not only severity but also the rate of onset and progression. Because of the latter, patients with RPE65-associated LCA can be treated from diagnosis up until their thirties or even forties.
In the new study, the researchers have focused on one of the rarest—and previously untreatable—flavors of LCA which affects the gene for AIPL1, which is essential for both the development and function of photoreceptor cells. This type of LCA is far more severe in effect, Michaelides says.
“They can’t get around in the dark. They’ve got no peripheral vision. Their central vision is virtually zero,” he explained.
“They can tell whether a light is on or off—if you shine a bright light at them, they might look towards it, for example.
“And then a smaller number of children with AIPL1 may be able to discern a large object really close up, or if it’s moving.”
Signs of AIPL1 issues in newborn children can include roving, almost shaking, eye movements; an inability to fix their eyes on anything, including their parents; and sleeping problems due to an inability to tune into the day/night cycles that normally set our bodies’ circadian rhythms.
Unlike with RPE65, AIPL1-associated LCA has a tiny window of opportunity for treatment. After four years of age, the limited functional retinal tissue degenerates, leading to total and irreversible blindness.
In a study published in the journal The Lancet, Michaelides and his colleagues describe how they trialed their new gene therapy in four children—treating one eye in each, while leaving the other untreated to serve as a control for comparison’s sake.
The surgical procedure involves first temporarily removing the vitreous gel that fills the eye to gain access to the retina. Then a solution containing the viral vector is injected under the retina so that the virus can get to work installing the new genetic code into the photoreceptor cells.
The surgery, the researchers explain, takes only about an hour to complete, and the first signs of visual improvement can be reported within a matter of weeks.
Following up with the children three-to-four years after the procedure, the researchers found that the vision in the untreated eyes had notably deteriorated, whereas the treated eyes had all seen a significant improvement in vision.
“They go from ‘I can barely perceive light’ to ‘you can record vision on a chart,’” Michaelides explained.
In fact, he explains—if you picture a classic optometrist’s eye chart—the test patients ended up able to make out the first row (i.e. they had 20/200 vision, or they could see at 20 feet what a person with normal visual acuity [“20/20 vision”] could see at 200 feet).
Since completing their initial study, the researchers have now treated seven more children with AIPL1-LCA; in these cases, the gene therapy was applied to both eyes.
Put together, all the children have seen an improvement in their vision from the treatment—one even reaching 20/80 vision. This is a success rate that seems to even astonish Michaelides himself.
“It’s the fact that all eleven benefit. It’s not, say, four of the eleven—it’s all of them. It’s genuinely remarkable. It’d be hard to believe if it weren’t true,” the ophthalmologist said.
The researchers are now talking with various regulatory agencies in the U.K., Europe and U.S.—including the FDA—about getting the treatment approved for widespread use, a process which they expect to be complete in one-to-two years’ time.
Given that, to date, the researchers have only been able to monitor their patients for a few years after treatment, it is unclear how long lasting the improvements in vision will be—although Michaelides, certainly, is hopeful such will endure for the rest of their lives.
Yet even if it doesn’t, he notes, “the benefits they’ve accrued in terms of their other areas of development will be lifelong, you know, in terms of communication, behavior and mobility.”
These are benefits that Bradley and Jessica Haines have already seen in their son Harvey, who received the gene therapy in both of his eyes.
Before the operation, Bradley explained, Harvey struggled to be left in an environment that he wasn’t confident in. This made it hard for him to get to know his peers.
“Pre-surgery, his preference would be to hang out with adults or older children,” added Jessica.
“He’d come home from school and we’d say ‘who’d you play with today?’ and he’d say a teacher. That was something that was a bit of a concern for us, because obviously everybody wants their kids to have friends.”
But this all changed after the surgery, Jessica said. “We even noticed [among] our own kids… for the first time in forever, they started to really play together.
“They were playing, you know, role play; they were playing teachers and airplanes and all of these kinds of things that, at times, did require vision. We had never seen that before.”
She concluded: “It’s exciting to see him build some little friendships and some more relationships now.”
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Reference
Michaelides, M., Laich, Y., Wong, S. C., Oluonye, N., Zaman, S., Kumaran, N., Kalitzeos, A., Petrushkin, H., Georgiou, M., Tailor, V., Pabst, M., Staeubli, K., Maimon-Mor, R. O., Jones, P. R., Scholte, S. H., Georgiadis, A., van der Spuy, J., Naylor, S., Forbes, A., Dekker, T. M., Arulmuthu, E. R., Smith, A. J., Ali, R. R., & Bainbridge, J. W. B. (2025). Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study. The Lancet, 405, 648–57. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02812-5/fulltext
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