In a first for one of the most severe forms of childhood blindness, doctors in London have used gene therapy to restore vision in four children born with a rare genetic mutation (AIPL1 gene (Aryl-hydrocarbon-interacting protein-like 1). The treatment, recently profiled in The Guardian, involves injecting a functional copy of the AIPL1 gene beneath the retina using an adeno-associated virus (AAV) vector. The hour-long keyhole surgery helps photoreceptors convert light into sight. The specialists at Moorfields Eye Hospital emphasize that intervening early—before significant retinal damage occurs—was essential to the therapy’s success.
Over a five-year follow-up, all four children with the condition, AIPL1-related Leber congenital amaurosis (LCA), demonstrated sustained improvements in the treated eye. Some progressed from sensing only light and dark to recognizing faces, navigating rooms without assistance, and even making out large text. Meanwhile, their untreated eyes continued to degenerate—evidence that the disease itself remained active. While these gains appear durable so far, researchers caution that long-term data are still needed, especially regarding potential immune responses or surgical complications.
In the small study, all children had sustained improvements
Over a five-year follow-up, all four children demonstrated sustained improvements in the treated eye, according to a paper in The Lancet. Some progressed from sensing only light and dark to recognizing faces. They could navigate rooms without assistance, and even making out large text. Meanwhile, their untreated eyes continued to degenerate—evidence that the disease itself remained active. Additionally, the children’s treated eyes improved from only being able to perceive light to achieving visual acuity measurements of around 0.9 logMAR (roughly equivalent to seeing the top letter on a vision chart). Tests of visual cortex activity confirmed these improvements in the children who could complete the assessments. The paper also noted that imaging showed better preservation of retinal structure in the treated versus untreated eyes. The researchers stressed that long-term data are still needed, especially regarding potential immune responses or surgical complications.
The Guardian reports that another seven patients received the treatment after the first four. The restoration of sight in these children builds on the earlier success of Luxturna, the first FDA-approved gene therapy for a different LCA mutation (RPE65). Priced around $850,000 for both eyes in 2018, Luxturna showed that payers are willing to support transformative but expensive treatments under certain reimbursement models. The new AIPL1 therapy, backed by MeiraGTx and facilitated under the UK’s MHRA “Specials” license, signals growing industry confidence in ocular gene therapy.
The Guardian also reports that another seven patients received the treatment after the first four.
Other approaches to target blindness
Outside of the recent work to treat LCA, scientists are exploring a range of other approaches, briefly summarized below:
CRISPR gene editing: This approach includes the first-in-human CRISPR gene editing trial (Editas Medicine’s EDIT-101) targeted CEP290-related LCA10. Interim results (published in 2024) showed the treatment was safe and approximately 79% of participants had some measurable vision improvement, but only 3 of 14 met the criteria for robust “positive response.”
Cell-based therapies: Beyond gene therapies, researchers are also exploring cell-based approaches that aim to replace or rescue dying retinal cells. For instance, one strategy involves injecting retinal progenitor cells to preserve vision. One example is jCyte’s Phase 2b clinical trial for retinitis pigmentosa. Early results showed promising improvements in visual acuity compared to sham treatments. Further analyses confirmed gains in retinal function. Although still in early clinical testing, such therapies could eventually complement gene-based approaches to restore structural integrity to the retina.
Optogenetics for advanced degeneration: For patients whose photoreceptors are already lost, optogenetics aims to make remaining retinal cells light-sensitive by introducing genes that encode light-activated proteins (opsins). GenSight Biologics’ GS030 therapy recently showed partial vision recovery, as documented in a Nature Medicine case report. Additional details highlighted gains in motion detection for a patient using specialized goggles to amplify incoming light signals.
Expanding the pipeline: Meanwhile, a rapidly diversifying pipeline targets various genetic forms of blindness, including mutations in RPGR (retinitis pigmentosa) and CEP290 (Leber congenital amaurosis 10). Preliminary findings from a Biogen-sponsored XLRP gene therapy trial reported 6-month safety and efficacy data, although some patients experienced retinal inflammation that resolved with oral corticosteroids. These ongoing studies reflect a broadening array of therapeutic avenues as researchers work to address the many genetic variants underlying inherited retinal diseases.
