ArticleProceedings of the National Academy of Sciences of the United States of America2015
Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. 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 70 papers, 1 of them a synthesis 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.
A Phase 2 Multicenter, Double-Masked, Randomized, Placebo-Controlled Study to Investigate the Long Term Safety, Tolerability, Pharmacokinetics and Effects of ALK-001 on the Progression of Stargardt Disease
A Phase 2 Multicenter, Double-Masked, Randomized, Placebo-Controlled Study to Investigate the Long Term Safety, Tolerability, Pharmacokinetics and Effects of ALK-001 on the Progression of Stargardt Disease
Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Visual cycle modulators versus placebo or observation for the prevention and treatment of geographic atrophy due to age-related macular degeneration.The Cochrane database of systematic reviews · 2020Pooled it
- Gildeuretinol Acetate versus Placebo for Geographic Atrophy Secondary to Age-Related Macular Degeneration: The Study of ALK-001 in Geographic Atrophy Randomized Clinical Trial.Ophthalmology. Retina · 2026Trial
- DGAT1-associated lipid-retinoid dysregulation correlates with metabolic impairment in the RPE of Stargardt disease.iScience · 2026Article
- Therapeutic Efficacy of Multi-Characteristic Opsin Gene Therapy in a Mouse Model of Stargardt Disease.Bioengineering (Basel, Switzerland) · 2026Article
- Nutritional supplements: current evidence for retinitis pigmentosa and Stargardt disease.Current opinion in ophthalmology · 2026Review
- Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy.Biomolecules · 2025Review
- Dysregulated DNA Methylation inInternational journal of molecular sciences · 2025Article
- Retinoid dynamics in vision: from visual cycle biology to retina disease treatments.Pharmacology & therapeutics · 2025Review
- Expansion of The ABCA4-Associated Retinopathy Spectrum: Might Vitamin A Supplementation Have Contributed to a More Severe Phenotype?Investigative ophthalmology & visual science · 2025Article
- Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.Cell communication and signaling : CCS · 2025Review
- Review
- Synchronized Photoactivation of T4K Rhodopsin Causes a Chromophore-Dependent Retinal Degeneration That Is Moderated by Interaction with Phototransduction Cascade Components.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Retinoic acid related orphan receptor α is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD.Gene therapy · 2024Article
- Stargardt macular dystrophy and therapeutic approaches.The British journal of ophthalmology · 2024Review
- Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.Antioxidants (Basel, Switzerland) · 2023Review
- Discovery of Nonretinoid Inhibitors of CRBP1: Structural and Dynamic Insights for Ligand-Binding Mechanisms.ACS chemical biology · 2023Article
- Updates on Emerging Interventions for Autosomal RecessiveJournal of clinical medicine · 2023Review
- LipidUNet-Machine Learning-Based Method of Characterization and Quantification of Lipid Deposits Using iPSC-Derived Retinal Pigment Epithelium.Journal of visualized experiments : JoVE · 2023Article
- Deuterium in drug discovery: progress, opportunities and challenges.Nature reviews. Drug discovery · 2023Review
10 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
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Stargardt disease, an ATP-binding cassette, subfamily A, member 4 (ABCA4)-related retinopathy, is a genetic condition characterized by the accelerated accumulation of lipofuscin in the retinal pigment epithelium, degeneration of the neuroretina, and loss of vision. No approved treatment exists. Here, using a murine model of Stargardt disease, we show that the propensity of vitamin A to dimerize is responsible for triggering the formation of the majority of lipofuscin and transcriptional dysregulation of genes associated with inflammation. Data further demonstrate that replacing vitamin A with vitamin A deuterated at the carbon 20 position (C20-D3-vitamin A) impedes the dimerization rate of vitamin A--by approximately fivefold for the vitamin A dimer A2E--and subsequent lipofuscinogenesis and normalizes the aberrant transcription of complement genes without impairing retinal function. Phenotypic rescue by C20-D3-vitamin A was also observed noninvasively by quantitative autofluorescence, an imaging technique used clinically, in as little as 3 months after the initiation of treatment, whereas upon interruption of treatment, the age-related increase in autofluorescence resumed. Data suggest that C20-D3-vitamin A is a clinically amiable tool to inhibit vitamin A dimerization, which can be used to determine whether slowing the dimerization of vitamin A can prevent vision loss caused by Stargardt disease and other retinopathies associated with the accumulation of lipofuscin in the retina.
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.