In a groundbreaking medical first, doctors have restored vision in children who were born almost completely blind. Four young children with a rare inherited eye disorder gained meaningful sight after a single gene therapy treatment​.

The children went from only being able to tell light from darkness to being able to recognize objects and shapes, and in some cases, even read. . sa consultant ophthalmologist involved in the trial, calling the outcomes “hugely impressive” and a potential “paradigm shift” in treating early blindness​.

“We have, for the first time, an effective treatment for the most severe form of childhood blindness,” said Professor Michel Michaelides, one of the researchers involved in the study. Michaelidis added that this is “pretty amazing” and “a potential paradigm shift” for children suffering from this condition.

Curing blindness

The four children were born with Leber Congenital Amaurosis type 4 (LCA4). This is a severe form of retinal dystrophy caused by mutations in the AIPL1 gene. Children with this rare genetic defect are typically certified legally blind from birth and there are no conventional cures. Glasses or surgery can’t fix the problem because the root cause is a faulty gene preventing the eye’s light-sensing cells from working properly.

​This is where gene therapy comes in.

The procedure consists of an injection containing healthy copies of the AIPL1 gene into the retina of one eye during a delicate “keyhole” surgery​. These copies are put inside a harmless virus, which helps them to enter the retinal cells and replace the defective gene. Researchers selected four children (from the US, Turkey, and Tunisia) for the trial. They received the therapy in only one eye.

All of the surgeries went well. Here, the parents of one of the children, Jace, describe how quick the recovery was:

“After the operation, Jace was immediately spinning, dancing and making the nurses laugh. He started to respond to the TV and phone within a few weeks of surgery and, within six months, could recognise and name his favourite cars from several metres away; it took his brain time, though, to process what he could now see. Sleep can be difficult for children with sight loss, but he falls asleep much more easily now, making bedtimes an enjoyable experience.”

Remarkably, all four children experienced dramatic improvements in vision in their treated eye over the next several years​. They described considerable improvements in visual behaviour from 4 weeks after the intervention. By about 3–4 years after the gene therapy, tests showed the treated eyes improved from essentially zero vision to roughly 20/200 on the vision chart. When someone has 20/200 vision, it means that at 20 feet away from an eye chart, they can see only as much detail as a person with normal (20/20) vision would see at 200 feet. It’s not perfect, but it’s still a massive improvement.

The parents of the children described the results as “amazing” and said they felt “lucky” to be involved in the trial.

Gene therapy shows great potential

Several ophthalmological conditions can be addressed through gene therapy. X-linked retinitis pigmentosa (a progressive vision loss in boys) and choroideremia (an inherited disease that causes progressive damage the retina) are currently in clinical trials with gene therapies. Even common diseases such as age-related macular degeneration are being targeted with gene-based treatments. For example, gene therapy is being trialed for delivering long-term anti-VEGF drugs to the eye.

The eye has proven to be a fertile testing ground for gene therapy, but it’s not the only one. In 2019, the FDA approved a gene therapy for spinal muscular atrophy (SMA) — a deadly neuromuscular disorder in infants — which has enabled babies who would have died before age two to grow up healthy. Another gene therapy has effectively cured certain patients with immunodeficiency disorders (often called “bubble boy” disease) by reprogramming their bone marrow cells with a correct gene. Trials are also underway for gene therapies for sickle cell anemia, hemophilia, and various metabolic diseases.

Each of these successes, like the one for AIPL1 blindness, can have transformational power in the lives of many.

A promising future

These treatments, however, won’t come overnight. Manufacturing them is complex and often extremely expensive. Scaling up production may cut down on some of the costs, but it’s not clear how much. There are also scientific hurdles to overcome: not all genes are as straightforward to deliver as AIPL1 or RPE65.

Some genetic eye diseases are caused by very large genes or by mutations in many different genes, requiring alternative strategies like gene editing or RNA therapies. Lastly, regulators and health systems will need to adapt to evaluate and provide these one-time treatments that can have lifelong benefits.

Yet, the progress is undeniable. Gene therapy, once seen as a futuristic idea, is rapidly becoming a real-world solution for blindness and other health conditions. Something that wasn’t even imaginable a few decades ago is now a reality. Doctors involved in the trial are working on the next steps. They aim to treat the second eyes of these children now that safety is clear and to open the therapy to more patients.

The study was published in The Lancet.