Medics preserve sight in children with rare genetic eye condition in world first

Medics in the UK have become the first in the world to successfully administer a pioneering gene therapy that preserves sight in young children with an extremely rare genetic condition that usually causes blindness in the first few years of life.

The patients, who were essentially blind at birth, can now see shapes, find toys, recognise faces, and in some cases, can even read and write.

The procedure, which takes around an hour, involves injecting healthy copies of the affected gene into the back of one eye to “kick start” sensitivity.

The condition is so rare that the first children to have the therapy were selected from overseas.

Specialists hope it can be made more widely available in the UK and elsewhere as a licensed treatment.

Four children were selected for the gene therapy by specialists from Moorfields Eye Hospital and UCL Institute of Ophthalmology in 2020.

All had severe retinal dystrophy known as leber congenital amaurosis (LCA), an inherited condition that causes vision loss due to a defect in the AIPL1 gene.

This gene is important for the function of photoreceptors, light-sensing cells in the retina that convert light into electrical signals that the brain interprets as vision.

Professor James Bainbridge, consultant retinal surgeon at Moorfields Eye Hospital and professor of retinal studies at UCL Institute of Ophthalmology, told the PA news agency: “Typically, they can only distinguish light and dark, and that little sight they will lose within the first few years of life.

“So what we found is that by providing the gene to their eyes that’s otherwise lacking, we can substantially improve their sight, and this appears to have a positive impact on their general development.”

The operations were carried out at Great Ormond Street Hospital in London, with medics performing keyhole surgery on patients aged between one and two to access the eye.

Healthy copies of the AIPL1 gene, contained in a harmless virus, were then injected into the retina, the light-sensitive layer of tissue at the back of the eye.

“The effect of that is to kick start, if you like, the sensitivity of the retina,” Prof Bainbridge added.

“And the expectation is that that might have some benefit to their sight within a few weeks or months, and indeed we were delighted to see that that was indeed the case.”

The gene therapy was only administered into one eye per patient to overcome any potential safety issues.

Given the rarity of LCA, patients were found outside the UK, with families travelling to London from the US, Turkey and Tunisia.

“This particular condition is really very rare,” Prof Bainbridge said.

“And so we were able to extend the possibility of treatment globally, and the first families who approached us with children eligible happened to be from outside the UK.

“The hope is this treatment will become available to children in the UK and elsewhere as a licensed treatment.”

The children were followed up over several years to determine the long-term effect of the therapy.

Researchers used a number of ways to assess the children’s sight, including reading letters and using scans of the eye to judge the preservation of cells in the retina.

“The parents were delighted, frankly, to see that the sight of the treated eye improved so substantially,” Prof Bainbridge told PA.

“They were very relieved and very positive about the findings.

“The parents describe the children gaining confidence in terms of their mobility, their independence, their ability to find their way around, also in terms of their recognition of shapes and faces and images.

“Some children are even able to read and write following the intervention which is something that one would absolutely not expect in this condition, untreated.”

Brendan and DJ, who did not wish to share their surname, travelled from Connecticut in the US for the treatment in September 2020.

Their son Jace, who is now six, was around two when he had the procedure.

Jace’s mother DJ told PA it has been “amazing to watch him”.

She added: “There’s such a need to amplify how this treatment has been working, because we think about all the other parents that are sitting there with their five-month-old scared out of their mind about what their future is going to look like.

“We were so lucky to have been able to have this option available to us and to Jace.”

UCL developed the treatment using a manufacturer’s special licence, granted by the Medicines and Healthcare Regulatory Agency (MHRA), which allows the production of unlicensed medicines for special clinical needs.

It was supported by clinical stage gene therapy company MeiraGTx.

After the procedures, the children were seen at the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust’s clinical research facility.

Prof Bainbridge told PA it is hoped the therapy will be made more widely available in the UK and beyond, and will eventually be used to treat both eyes.

“The findings provide confidence that this particular approach can be helpful in even a severe condition,” he said.

“And of course, the hope is that the same approach might be helpful for children with more common conditions in the future.

“A similar gene therapy has been available for a similar form of genetic blindness on the NHS in the UK for some five years, but the findings of this particular treatment indicate that the same approach can work for a condition which is even more severe.

“The expectation and the hope is that that will be available to children for treatment in both eyes.”

Since the initial treatments were administered, a further seven patients have been treated at Evelina London Children’s Hospital by specialists from St Thomas’ Hospital, Great Ormond Street and Moorfields.

Professor Michel Michaelides, a consultant retinal specialist at Moorfields and professor of ophthalmology at the UCL Institute of Ophthalmology, said: “We have, for the first time, an effective treatment for the most severe form of childhood blindness, and a potential paradigm shift to treatment at the earliest stages of the disease.

“The outcomes for these children are hugely impressive and show the power of gene therapy to change lives.”

A research paper published in the Lancet has outlined the findings from the trial.