Trial reportProceedings of the National Academy of Sciences of the United States of America2008
Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 408 papers, 2 of them syntheses that pooled 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.
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.
Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-CBSB-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations (Clinical Trials of Gene Therapy for Leber Congenital Amaurosis)
Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations
Who cites it
408 citing papers in PubMed, 2 syntheses or guidelines pooled it, 663 citations in OpenAlex.
- ISCEV and IPS guideline for the full-field stimulus test (FST).Documenta ophthalmologica. Advances in ophthalmology · 2024Guideline
- 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
- 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
- Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy.Human gene therapy · 2018Trial
- Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for α-1-antitrypsin deficiency.Proceedings of the National Academy of Sciences of the United States of America · 2017Trial
- Improvement and decline in vision with gene therapy in childhood blindness.The New England journal of medicine · 2015Trial
- Long-term effect of gene therapy on Leber's congenital amaurosis.The New England journal of medicine · 2015Trial
- Trial
- Cerebrospinal delivery of a bidirectional AAV9 vector improves optic nerve and retinal pathology in a sheep model of Tay-Sachs disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Full-Field Stimulus Threshold: A Key Functional Outcome Measure in Retinal Diseases and Clinical Trials.Journal of clinical medicine · 2026Review
- Review
- Test-retest variability of the full-field stimulus test in patients with retinitis pigmentosa: REPEAT Study Report No. 4.Acta ophthalmologica · 2026Article
- Rod-Cone Dystrophy Related WDR34 Is Essential for Ciliary Integrity and Survival of Mammalian Photoreceptor Cells.Investigative ophthalmology & visual science · 2026Article
- Sustained improvement in dark-adapted sensitivity but not BCVA after voretigene neparvovec treatment in a mainland Chinese child with biallelicFrontiers in pharmacology · 2026Article
- Culture of Human Retinal Explants as an Ex Vivo Model for Retinal Gene Therapy.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A Comprehensive Review of Clinically Applied Adeno-Associated Virus-Based Gene Therapies for Ocular Disease.Human gene therapy · 2025Review
- One down but many more to go: the state of gene therapy for inherited retinal disease.Regenerative medicine · 2025Review
- Small-Molecule Ligands of Rhodopsin and Their Therapeutic Potential in Retina Degeneration.International journal of molecular sciences · 2025Review
- Photoreceptor Disease at Ambiguous Transition Zones in Inherited Retinal Degenerations.Translational vision science & technology · 2025Article
- Increment Thresholds in Retinitis Pigmentosa: Association With Retinal Thickness.Investigative ophthalmology & visual science · 2025Article
348 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
The RPE65 gene encodes the isomerase of the retinoid cycle, the enzymatic pathway that underlies mammalian vision. Mutations in RPE65 disrupt the retinoid cycle and cause a congenital human blindness known as Leber congenital amaurosis (LCA). We used adeno-associated virus-2-based RPE65 gene replacement therapy to treat three young adults with RPE65-LCA and measured their vision before and up to 90 days after the intervention. All three patients showed a statistically significant increase in visual sensitivity at 30 days after treatment localized to retinal areas that had received the vector. There were no changes in the effect between 30 and 90 days. Both cone- and rod-photoreceptor-based vision could be demonstrated in treated areas. For cones, there were increases of up to 1.7 log units (i.e., 50 fold); and for rods, there were gains of up to 4.8 log units (i.e., 63,000 fold). To assess what fraction of full vision potential was restored by gene therapy, we related the degree of light sensitivity to the level of remaining photoreceptors within the treatment area. We found that the intervention could overcome nearly all of the loss of light sensitivity resulting from the biochemical blockade. However, this reconstituted retinoid cycle was not completely normal. Resensitization kinetics of the newly treated rods were remarkably slow and required 8 h or more for the attainment of full sensitivity, compared with <1 h in normal eyes. Cone-sensitivity recovery time was rapid. These results demonstrate dramatic, albeit imperfect, recovery of rod- and cone-photoreceptor-based vision after RPE65 gene therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.