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Little Harvey Haines has been given a new lease of life. Born with a rare eye condition severely affecting his sight, he struggled to communicate with children his own age, shied away from environments that he wasn't confident in and even found it difficult to play with his siblings. But all that has changed for him and a group of other children following a revolutionary new 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 two to three of every 10 million newborn babies, leads to profound visual impairments and legal blindness. In turn, this causes affected children to typically experience delayed and disrupted development across many areas including behavior, communication and mobility.
After trials of the new procedure, however, children that before could only play with toys by feeling them 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, or 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. This category of disorders is seen in roughly two to three 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.
Harvey's parents, Bradley and Jessica, explained his daily struggles before he received the gene therapy in his eyes, at age 3. "Pre-surgery, his preference would be to hang out with adults or older children," Jessica said. "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."
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.
Back in 2017, the U.S. Food and Drug Administration approved Luxturna, a prescription 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 8 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 age 30 or even 40 years old.
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 toward 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 persistent sleeping problems due to an inability to properly tune into the day/night cycles that normally set our bodies' circadian rhythms and regulate sleep patterns.
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 described how they trialed their new gene therapy in four children—treating one eye in each child, while leaving the other untreated to serve as a control for comparison's sake.
The surgical procedure involves first temporarily removing the gel-like vitreous substance that fills the eye to gain access to the delicate retina. Then, a specially prepared solution containing the viral vector is carefully 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 explained, takes only around 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 have 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 said.
In fact, he explained—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 LCA-AIPL1; 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 astonish even Michaelides. "It's the fact that all 11 benefit. It's not, say, four of the 11—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 the U.S.—including the FDA—about getting the treatment approved for more widespread use. They expect this process to be complete in around 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 went on to note: "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."
Harvey's mom Jessica agreed. "We even noticed [among] our own kids...for the first time in forever, they started to really play together," she said. "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
