Evidence map›Paper›PMID 39986747›Full record

ArticleLancet (London, England)2025

Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study.

Michel Michaelides, Yannik Laich, Sui Chien Wong, Ngozi Oluonye, Serena Zaman, Neruban Kumaran, Angelos Kalitzeos, Harry Petrushkin, Michalis Georgiou, Vijay Tailor and 14 more

Abstract read
PubMed Publisher
In one paragraph

Article in Lancet (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Restoring Sight: The Journey of AIPL1 from Discovery to Therapy.International journal of molecular sciences · 2025
    Review
  7. Article
  8. How infants look shapes what they learn.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Michel MichaelidesNIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK. Electronic address: michel.michaelides@ucl.ac.uk.
Yannik LaichNIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK; Eye Center, Faculty of Medicine, Freiburg University, Freiburg, Germany.
Sui Chien WongNIHR Moorfields Biomedical Research Centre, London, UK; Great Ormond Street Hospital for Children, London, UK.
Ngozi OluonyeNIHR Moorfields Biomedical Research Centre, London, UK; Great Ormond Street Hospital for Children, London, UK.
Serena ZamanNIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK.
Neruban KumaranUCL Institute of Ophthalmology, University College London, London, UK; Guy's and St Thomas' NHS Foundation Trust, London, UK.
Angelos KalitzeosNIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK.
Harry PetrushkinNIHR Moorfields Biomedical Research Centre, London, UK; Great Ormond Street Hospital for Children, London, UK.
Michalis GeorgiouNIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK.
Vijay TailorNIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK; Experimental Psychology, University College London, London, UK.
Marc PabstUCL Institute of Ophthalmology, University College London, London, UK; Experimental Psychology, University College London, London, UK.
Kim StaeubliUCL Institute of Ophthalmology, University College London, London, UK; Experimental Psychology, University College London, London, UK.
Roni O Maimon-MorUCL Institute of Ophthalmology, University College London, London, UK; Experimental Psychology, University College London, London, UK.
Peter R JonesUCL Institute of Ophthalmology, University College London, London, UK; Department of Optometry and Visual Sciences, City St George's, University of London, London, UK.
Steven H ScholteDepartment of Psychology, University of Amsterdam, Amsterdam, Netherlands.
Anastasios GeorgiadisMeiraGTx, London, UK.
Jacqueline van der SpuyUCL Institute of Ophthalmology, University College London, London, UK.
Stuart NaylorMeiraGTx, London, UK.
Alexandria ForbesMeiraGTx, London, UK.
Tessa M DekkerUCL Institute of Ophthalmology, University College London, London, UK; Experimental Psychology, University College London, London, UK.
Eugene R ArulmuthuUCL Institute of Ophthalmology, University College London, London, UK.
Alexander J SmithUCL Institute of Ophthalmology, University College London, London, UK; Centre for Gene Therapy and Regenerative Medicine, King's College London, London, UK.
Robin R AliNIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK; Guy's and St Thomas' NHS Foundation Trust, London, UK; Centre for Gene Therapy and Regenerative Medicine, King's College London, London, UK. Electronic address: robin.ali@kcl.ac.uk.
James W B BainbridgeNIHR Moorfields Biomedical Research Centre, London, UK; UCL Institute of Ophthalmology, University College London, London, UK. Electronic address: j.bainbridge@ucl.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRetinal dystrophy caused by genetic deficiency of AIPL1 causes severe and rapidly progressive impairment of sight from birth. We sought to evaluate whether early intervention by gene supplementation therapy was safe and could improve outcomes in children with this condition.

methodsThis non-randomised, single-arm, clinical study conducted in the UK involved four children aged 1·0-2·8 years with severe retinal dystrophy associated with biallelic disease-causing sequence variants in AIPL1. We designed a recombinant adeno-associated viral vector comprising the human AIPL1 coding sequence driven by a human rhodopsin kinase promoter region (rAAV8.hRKp.AIPL1). The product was manufactured under a Specials Licence from the Medicines and Health products Regulatory Authority (UK) and made available to affected children with local ethics approval. We administered the product to one eye of each child by subretinal injection. The children were prescribed oral prednisolone to protect against harm from inflammation. Outcome measures included visual acuity (as assessed with a novel touchscreen test), functional vision (assessed by observing and recording the children's visual behaviour and their ability to perform simple vision-guided tasks), visual evoked potentials (assessed by recording cortical electrophysiological responses to full-screen black-and-white flickering stimuli), and retinal structure (assessed with handheld optical coherence tomography [OCT] and widefield fundus imaging). To identify adverse effects, including inflammation and retinal detachment, we conducted ocular examinations using slit-lamp biomicroscopy and dilated fundoscopy. Safety was further assessed by testing of visual acuity, ophthalmoscopy, handheld OCT and widefield fundus imaging.

findingsPatients were selected for treatment between July 12, 2019, and March 16, 2020. Before intervention, the children's binocular visual acuities were limited to perception of light. At a mean of 3·5 years (range 3·0-4·1) after intervention, the visual acuities of the children's treated eyes had improved to a mean of 0·9 logarithm of the minimal angle of the minimum angle of resolution ([logMAR] range 0·8-1·0); visual acuities before intervention were equivalent to 2·7 logMAR. In contrast, the visual acuities of the children's untreated eyes became unmeasurable at the final follow-up. In the two children able to comply with testing, an objective test of visual acuity confirmed improvements in visual function, and measurement of visual evoked potentials showed enhanced activity of the visual cortex, specific to the treated eyes. In three of the children, structural lamination of the outer retina was better preserved in the treated eye than in the untreated eye, and, for all four children, retinal thickness appeared better preserved in the treated eye than in the untreated eye. The treated eye of one child developed cystoid macular oedema. No other safety concerns were identified.

interpretationOur findings indicate that young children with AIPL1-related retinal dystrophy benefited substantially from subretinal administration of rAAV8.hRKp.AIPL1, with improved visual acuity and functional vision and evidence of some protection against progressive retinal degeneration, without serious adverse effects.

fundingUK National Institute for Health Research and Moorfields Eye Charity.

Indexed as

Adaptor Proteins, Signal TransducingGenetic TherapyRetinal DystrophiesChild, PreschoolDependovirusFemaleHumansInfantMaleTomography, Optical CoherenceTreatment OutcomeVisual AcuityAdaptor Proteins, Signal TransducingAIPL1 protein, human

Identifiers

PMID39986747

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.