Therapy licence enables ‘life changing’ treatment for genetic blindness

All four patients have Leber congenital amaurosis (LCA), a genetic deficiency that affects the AIPL1 gene, leaving them initially with sufficient sight only to distinguish light and dark.

However, the condition results in the death of their retinal cells and, though classified as a rare genetic disease, is one of the commonest causes of legal blindness in childhood.

But the new treatment, developed by UCL Institute of Ophthalmology and Moorfields Eye Hospital, employed keyhole surgery to inject healthy copies of the AIPL1 gene inside a harmless virus into the back of the eye, to penetrate the retinal cells .

The therapy outlined in The Lancet after being monitored for outcomes over several years – demonstrated ‘life changing’ improvements in the patients’ eyesight, according to scientists and the children’s parents.

We have, for the first time, an effective treatment for the most severe form of childhood blindness, and a potential paradigm shift to treatment

Michel Michaelides, professor of ophthalmology, UCL Institute of Ophthalmology/consultant retinal specialist, Moorfields Eye Hospital

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

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

The medicine employed, AAV-AIPL1, is an investigational genetic medicine developed by the US clinical stage genetic medicine firm MeiraGTx.

UCL had to apply for a so-called Manufacturers “Specials” Licence granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in order to produce and use the product in the UK.

MSLs permit the manufacture and supply of unlicensed medicines, “specifically made for individual patients when no licensed equivalent exists to meet their unique clinical needs” but under strict quality control regulations. 

The rarity of the condition – estimated by MeiraGTx to affect one in 33,000 people – meant all four patients chosen were from overseas.

Each child received treatment to one eye only in an effort to limit safety risks. The UCL team reported each patient’s treated eye showed “remarkable improvements” while sight was lost in the untreated eye.

They added that this demonstrated the efficacy of gene therapy for early age treatment of the condition.

Funding from the National Institute for Health and Care Research (NIHR), MeiraGTx and Moorfields Eye Charity donors helped enable the pioneering operations.

MeiraGTx also supported production, storage, quality assurance and released and supplied the medicine for treatment via its MSL. The procedure took place at Great Ormond Street Hospital with patient assessment at NIHR Moorfields Clinical Research Facility, and research infrastructure supplied by NIHR Moorfields Biomedical Research Centre.

Professor Robin Ali, of UCL Institute of Ophthalmology and King’s College London Centre for Gene Therapy and Regenerative Medicine commented: “This work demonstrates the importance of UK clinical academic centre manufacturing facilities and MHRA MSLs in making advanced therapies available to people with rare conditions.”

AIPL1 is not the first instance of gene therapy being employed to treat genetic blindness: Another, (RPE65 deficiency) has been a legally sanctioned therapy available on the NHS since 2020.

The UCL team is now seeking to make AIPL1 treatment available more widely, with researchers saying the recent findings suggest other forms of inherited blindness might eventually be treated via genetic medicines.

Pic: Victor Freitas