King's College London

The treatment, delivered through Moorfields Eye Hospital and UCL Institute of Ophthalmology, was supported by MeiraGTx and involved researchers from the King’s Centre for Gene Therapy and Regenerative Medicine.

The children were born with a severe impairment to their sight due to a rare genetic deficiency that affects the 'AIPL1' gene. The condition means those affected are born with only sufficient sight to distinguish between light and darkness. The gene defect causes the retinal cells to malfunction and die, with children affected being legally certified as blind from birth. The new treatment is designed to enable the retinal cells to work better and to survive longer.

The procedure, developed by UCL scientists, consists of injecting healthy copies of the gene into the retina, at the back of the eye through keyhole surgery. These copies are contained inside a harmless virus, so can penetrate the retinal cells and replace the defective gene.

The condition is very rare, and the first children identified were from overseas. To mitigate any potential safety issues, the first four children received this novel therapy in one eye only. All four saw remarkable improvements in the treated eye over the following three to four years, but lost sight in their untreated eye.

The outcomes of the new treatment, reported in The Lancet, show that gene therapy at an early age can dramatically improve sight for children with this condition - one that is rare and particularly severe. Successful gene therapy for another form of genetic blindness (RPE65 deficiency) has been available on the NHS since 2020. These new findings offer hope that children affected by both rare and more common forms of genetic blindness may in time also benefit from genetic medicine. The team is now exploring the means to make this new treatment more widely available.

Professor Robin Ali, Professor of Human Molecular Genetics at King’s and co-senior author of the paper, was involved with the work while in his previous role at the UCL Institute of Ophthalmology. At UCL, his team played a key role in development of the gene therapy, including manufacturing the clinical grade gene therapy vector at a facility established and directed by Professor Ali.

Since moving to King’s as the Director of the Centre for Gene Therapy & Regenerative Medicine and the Gene Therapy Vector Facility, Professor Ali continues to apply his extensive experience in gene-based therapies to develop advanced therapies for eye diseases.

Professor James Bainbridge, consultant retinal surgeon at Moorfields Eye Hospital and professor of retinal studies at UCL Institute of Ophthalmology, said: "Sight impairment in young children has a devastating effect on their development. Treatment in infancy with this new genetic medicine can transform the lives of those most severely affected."

Professor Michel Michaelides, consultant retinal specialist at Moorfields Eye Hospital and professor of ophthalmology at the UCL Institute of Ophthalmology, commented: " 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.”

The treatment was developed and manufactured at UCL under an MSL held by UCL. The procedure to administer the treatment to the affected children took place at Great Ormond Street Hospital, and the children were seen at the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust’s Clinical Research Facility.

The work was partially funded by the National Institute for Health and Care Research (NIHR), Meira GTx and Moorfields Eye Charity, thanks to the generosity of donors. Moorfields Eye Charity has also supported Professor Bainbridge’s work as the professor of retinal studies, enabling the expansion of this programme of experimental medicine including the initiation of gene therapy trials.

MeiraGTx supported production, storage, quality assurance and released and supplied it for treatment under their MSL.

Article adapted from Moorfields Eye Hospital press release.