ArticleProceedings of the National Academy of Sciences of the United States of America2013
Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 3 of them syntheses that pooled it.
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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.
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.
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Who cites it
255 citing papers in PubMed, 3 syntheses or guidelines pooled it, 438 citations in OpenAlex.
- Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With Retinal Degeneration: A Systematic Review and Meta-Analysis.Translational vision science & technology · 2023Pooled it
- The effect of human gene therapy for RPE65-associated Leber's congenital amaurosis on visual function: a systematic review and meta-analysis.Orphanet journal of rare diseases · 2020Pooled it
- [Gene therapy as a treatment concept for inherited retinal diseases].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2015Pooled it
- Recovery of cone-mediated vision in Lebercilin associated retinal ciliopathy after gene therapy: One-year results of a phase I/II trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Trial
- Immune function in X-linked retinoschisis subjects in an AAV8-RS1 phase I/IIa gene therapy trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Trial
- Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy.Human gene therapy · 2018Trial
- Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial.Lancet (London, England) · 2017Trial
- Long-term effect of gene therapy on Leber's congenital amaurosis.The New England journal of medicine · 2015Trial
- Improvement and decline in vision with gene therapy in childhood blindness.The New England journal of medicine · 2015Trial
- Four-Year Structural and Functional Outcomes of the First Subretinal Voretigene Neparvovec-rzyl Treatment for RPE65-Associated Inherited Retinal Dystrophy in South Korea.Korean journal of ophthalmology : KJO · 2026Article
- Attenuating AAV-triggered innate immunity in the adult mouse nervous systemActa pharmaceutica Sinica. B · 2026Article
- Combination gene therapy with AAV based RPE65 and survivin vectors sustains phenotypic rescue in neural retina of LCA2 mice.Molecular and cellular biochemistry · 2026Article
- Assessing the Relationship between Foveal Cone Density, Outer Nuclear Layer Thickness and Foveal Morphology.Ophthalmology science · 2026Article
- Molecular mechanisms limiting the AAV gene therapy treatment window in mouse models of blue cone monochromacy.Communications biology · 2025Article
- Ocular gene therapy as a sustained drug delivery system: pharmacokinetic and genokinetic perspectives.Journal of medicine and life · 2025Review
- Single-Cell Transcriptomics in Inherited Retinal Dystrophies: Current Findings and Emerging Perspectives.Genes · 2025Review
- Novel photoreceptor-specific promoters for gene therapy in mid- to late-stage retinal degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- RP1 Dual-AAV Gene Therapy Preserves Retinal Structure and Ameliorates Photoreceptor Degeneration in a Murine Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
- Safety and efficacy of MCO-010 optogenetic therapy in patients with Stargardt disease in USA (STARLIGHT): an open-label multi-center Ph2 trial.EClinicalMedicine · 2025Article
- Addressing Challenges in Developing Treatments for Inherited Retinal Diseases: Recommendations From the Third Monaciano Symposium.Translational vision science & technology · 2025Review
195 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5-11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term.
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Registered trials
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.