ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Long-Term Structural Outcomes of Late-Stage RPE65 Gene Therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
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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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Gene Therapy Using Recombinant Adeno-Associated Virus for Leber Congenital Amaurosis Induced by RPE65 Mutation.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- AAV-delivered engineered suppressor tRNA rescues visual function in mice with an inherited retinal disease.Nature communications · 2025Article
- Impact of PEGylation and hyaluronan functionalization on lipoplex-mediated mRNA delivery to the canine retina.Drug delivery · 2025Article
- Review
- 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
- Deep Learning-Based Retinal Layer Segmentation in Optical Coherence Tomography Scans of Patients with Inherited Retinal Diseases.Klinische Monatsblatter fur Augenheilkunde · 2025Article
- Canine models of inherited retinal diseases: from neglect to well-recognized translational value.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- "Seeing Stars": The Gene Therapy Revolution.Advances in experimental medicine and biology · 2025Article
- Ocular Gene Therapy: An Overview of Viral Vectors, Immune Responses, and Future Directions.The Yale journal of biology and medicine · 2024Review
- Glial Cell Responses and Gene Expression Dynamics in Retinas of Treated and Untreated RPE65 Mutant Dogs.Investigative ophthalmology & visual science · 2024Article
- Gene Therapy for Retinitis Pigmentosa: Current Challenges and New Progress.Biomolecules · 2024Review
- Ciliary tip actin dynamics regulate photoreceptor outer segment integrity.Nature communications · 2024Article
- Sphingolipid biosynthetic inhibitor L-Cycloserine prevents oxidative-stress-mediated death in an in vitro model of photoreceptor-derived 661W cells.Experimental eye research · 2024Article
- Cell-cell interaction in the pathogenesis of inherited retinal diseases.Frontiers in cell and developmental biology · 2024Review
- Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration.Stem cells translational medicine · 2023Article
- Gene Therapy in Hereditary Retinal Dystrophies: The Usefulness of Diagnostic Tools in Candidate Patient Selections.International journal of molecular sciences · 2023Review
- [Gene therapy in ophthalmology].Die Ophthalmologie · 2023Review
- Genome editing in the treatment of ocular diseases.Experimental & molecular medicine · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The form of hereditary childhood blindness Leber congenital amaurosis (LCA) caused by biallelic RPE65 mutations is considered treatable with a gene therapy product approved in the US and Europe. The resulting vision improvement is well accepted, but long-term outcomes on the natural history of retinal degeneration are controversial. We treated four RPE65-mutant dogs in mid-life (age = 5-6 years) and followed them long-term (4-5 years). At the time of the intervention at mid-life, there were intra-ocular and inter-animal differences in local photoreceptor layer health ranging from near normal to complete degeneration. Treated locations having more than 63% of normal photoreceptors showed robust treatment-related retention of photoreceptors in the long term. Treated regions with less retained photoreceptors at the time of the intervention showed progressive degeneration similar to untreated regions with matched initial stage of disease. Unexpectedly, both treated and untreated regions in study eyes tended to show less degeneration compared to matched locations in untreated control eyes. These results support the hypothesis that successful long-term arrest of progression with RPE65 gene therapy may only occur in retinal regions with relatively retained photoreceptors at the time of the intervention, and there may be heretofore unknown mechanisms causing long-distance partial treatment effects beyond the region of subretinal injection.
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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.