How gene therapy is changing the outlook for inherited blindness

As a baby, Jace could distinguish light from dark, but little more. After receiving experimental gene therapy, he began responding to screens within weeks. Six months later, his mother said that he could recognise his favourite cars from several metres away.

Rather than replacing lost cells, gene therapy takes a different path: it helps the cells that remain to work again.

When the instructions are wrong

Genes contain instructions for making proteins. Faults in genes needed by the retina can disrupt vision and cause its light-sensing cells, the photoreceptors, to die. Leber congenital amaurosis (LCA) describes a group of inherited disorders causing severe sight loss early in life. One particularly severe form involves the AIPL1 gene.

A virus as a courier

Gene supplementation delivers a working copy of a gene using an adeno-associated virus (AAV): a harmless virus, modified to carry the gene into cells (Figure 1). Injected beneath the retina (Figure 2), it carries instructions into surviving cells so they can produce the needed protein. The new gene sits alongside the cell’s own DNA rather than replacing or rewriting it. This approach depends on having cells left to treat.

An established treatment

Luxturna, the first approved gene therapy for an inherited retinal disease, uses an AAV to deliver working copies of the RPE65 gene beneath the retina. It treats people with faults in both copies of this gene, which makes an enzyme critical for the visual cycle, the chain of chemical reactions that lets the retina turn light into signals for the brain. Without it, photoreceptors gradually die. Its 2017 randomised trial, run at two sites in the USA and funded by its developer, Spark Therapeutics, enrolled 31 people. At one year, 13 of the 20 treated participants assessed could navigate an obstacle course at the dimmest light level tested, compared with none of nine controls.

NHS England agreed to fund Luxturna in 2019. The reported list price was £613,410 per patient, with a confidential NHS discount. The benefit was better navigation in low light; however, this should not be read as a promise of normal sight.

Since approval, studies of patients treated in routine care have confirmed gains in light sensitivity, but patches of retinal thinning (chorioretinal atrophy) were found in around 3 in 10 cases, and what this means in the long term is still unclear.

Treating children early

A 2025 Lancet study, led by a team from Moorfields Eye Hospital and University College London, reported AIPL1 gene therapy in four children aged one to 2.8 years. Each received treatment in one eye. Before treatment, the children could perceive only light. After an average of 3.5 years, visual acuity (the sharpness of vision) in the treated eyes had improved from an estimated pretreatment equivalent of 2.7 logMAR to a mean of 0.9. Lower scores indicate sharper vision: this was a substantial improvement, although sight remained impaired. In the untreated eyes, left to the natural course of the disease, acuity could no longer be measured by the end of the study.

Tests of the brain’s electrical response to light, called visual evoked potentials, showed increased activity in the visual part of the brain in the two children able to complete them. One child developed swelling at the macula, the central retina; no other safety concerns were identified. However, with only four children in this study, more children will need to be treated and followed for longer before we know how often complications occur.

“Treatment in infancy with this new genetic medicine can transform the lives of those most severely affected,” said Professor James Bainbridge, the study’s senior author. The treatment’s developer, MeiraGTx, still describes it as investigational.

Editing the gene itself

CRISPR, a tool that cuts DNA at a precise point, offers another approach. A treatment called EDIT-101 uses it to cut out one particular faulty stretch of DNA in the CEP290 gene, so that cells can make the protein properly again (Figure 3).

The 2024 BRILLIANCE trial, run by Mass Eye and Ear, Oregon Health & Science University and the University of Pennsylvania with the developer Editas Medicine, involved 14 people, 11 of whom improved on at least one of four measures: visual acuity, light sensitivity, navigation and quality of life. Only four people, however, gained a clinically meaningful improvement in visual acuity. No treatment- or procedure-related serious adverse events were recorded, but longer follow-up remains important.

Hope with limits

These treatments are not a universal cure: each targets a particular gene or genetic variant, and none can revive photoreceptors that have already died. Yet for families such as Jace’s, seeing their child recognise his favourite cars from across a room can mark a profound change.

Written by S'ad Shaikh

Relate articles: rAAV gene therapy / Vision loss and neurocognition / Bionic implants for the visually impaired / Gene therapy for deafness

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