ArticlePediatric nephrology (Berlin, Germany)2019
The aminoglycoside geneticin permits translational readthrough of the CTNS W138X nonsense mutation in fibroblasts from patients with nephropathic cystinosis.
Article in Pediatric nephrology (Berlin, Germany), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX-02 in Patients With Nephropathic Cystinosis.Journal of clinical pharmacology · 2021Trial
- Advances in Pharmacological Treatments for Cystinosis: Cysteamine and Its Alternatives.ACS pharmacology & translational science · 2026Review
- Long-term outcomes in nephropathic cystinosis: a review.Pediatric nephrology (Berlin, Germany) · 2026Review
- High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs.Nucleic acids research · 2025Article
- Review
- Article
- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- Cystinosis: Status of research and treatment in India and the world.Journal of biosciences · 2023Article
- Evaluation of Pharmacological Rescue of Melanocortin-4 Receptor Nonsense Mutations by Aminoglycoside.Life (Basel, Switzerland) · 2022Article
- Review
- Nephropathic cystinosis: an update on genetic conditioning.Pediatric nephrology (Berlin, Germany) · 2021Review
- A no-nonsense approach to hereditary kidney disease.Pediatric nephrology (Berlin, Germany) · 2020Review
- Precision Medicine for Lysosomal Disorders.Biomolecules · 2020Review
- Germline CRISPR/Cas9-Mediated Gene Editing Prevents Vision Loss in a Novel Mouse Model of Aniridia.Molecular therapy. Methods & clinical development · 2020Article
- Absence of p.R50XDisease models & mechanisms · 2020Article
- A breakthrough in readthrough? Could geneticin lead the way to effective treatment for cystinosis nonsense mutations?Pediatric nephrology (Berlin, Germany) · 2019Article
- The novel aminoglycoside, ELX-02, permits CTNSW138X translational read-through and restores lysosomal cystine efflux in cystinosis.PloS one · 2019Article
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7 authors at 4 institutions in 2 countries.
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Abstract
backgroundCystinosis is an ultrarare disorder caused by mutations of the cystinosin (CTNS) gene, encoding a cystine-selective efflux channel in the lysosomes of all cells of the body. Oral therapy with cysteamine reduces intralysosomal cystine accumulation and slows organ deterioration but cannot reverse renal Fanconi syndrome nor prevent the eventual need for renal transplantation. A definitive therapeutic remains elusive. About 15% of cystinosis patients worldwide carry one or more nonsense mutations that halt translation of the CTNS protein. Aminoglycosides such as geneticin (G418) can bind to the mammalian ribosome, relax translational fidelity, and permit readthrough of premature termination codons to produce full-length protein.
methodsTo ascertain whether aminoglycosides permit readthrough of the most common CTNS nonsense mutation, W138X, we studied the effect of G418 on patient fibroblasts.
resultsG418 treatment induced translational readthrough of CTNS
conclusionsReduction in intracellular cystine indicates that the CTNS protein produced is functional as a cystine transporter. Interestingly, similar effects were seen even in W138X compound heterozygotes. These studies establish proof-of-principle for the potential of aminoglycosides to treat cystinosis and possibly other monogenic diseases caused by nonsense mutations.
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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.