ArticlePloS one2019
The novel aminoglycoside, ELX-02, permits CTNSW138X translational read-through and restores lysosomal cystine efflux in cystinosis.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of ELX-02 in Healthy Subjects.Clinical pharmacology in drug development · 2021Trial
- Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX-02 in Patients With Nephropathic Cystinosis.Journal of clinical pharmacology · 2021Trial
- RFFL-mediated protein quality control limits functional rescue of TRID-CFTR modulator combination therapy for cystic fibrosis nonsense mutations.Cellular and molecular life sciences : CMLS · 2026Article
- Ribosomal read through as an alternative therapy for patients with hemophilia with nonsense mutations.Journal of thrombosis and haemostasis : JTH · 2026Article
- Treatment Approaches for Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2026Review
- Recovery of α-L-fucosidase in fucosidosis nonsense variants by readthrough stimulation and release factor degradation.Disease models & mechanisms · 2026Article
- Review
- Novel readthrough agent suppresses nonsense mutations and restores functional type VII collagen and laminin 332 in epidermolysis bullosa.Molecular therapy. Nucleic acids · 2024Article
- Identification of novel small molecule-based strategies of COL7A1 upregulation and readthrough activity for the treatment of recessive dystrophic epidermolysis bullosa.Scientific reports · 2024Article
- Mechanisms and Delivery of tRNA Therapeutics.Chemical reviews · 2024Review
- Systematic and quantitative analysis of stop codon readthrough in Rett syndrome nonsense mutations.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Article
- Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease.Cell stem cell · 2024Article
- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- Balancing Nonsense Mutation Readthrough and Toxicity of Designer Aminoglycosides for Treatment of Genetic Diseases.ACS medicinal chemistry letters · 2023Article
- The synthetic aminoglycoside ELX-02 induces readthrough of G550X-CFTR producing superfunctional protein that can be further enhanced by CFTR modulators.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Alport Syndrome: Clinical Spectrum and Therapeutic Advances.Kidney medicine · 2023Review
- Advances in Drug Discovery Targeting Lysosomal Membrane Proteins.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Use of 2,6-diaminopurine as a potent suppressor of UGA premature stop codons in cystic fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCystinosis is a rare disorder caused by recessive mutations of the CTNS gene. Current therapy decreases cystine accumulation, thus slowing organ deterioration without reversing renal Fanconi syndrome or preventing eventual need for a kidney transplant.15-20% of cystinosis patients harbour at least one nonsense mutation in CTNS, leading to premature end of translation of the transcript. Aminoglycosides have been shown to permit translational read-through but have high toxicity level, especially in the kidney and inner ear. ELX-02, a modified aminoglycoside, retains it read-through ability without the toxicity. METHODS AND
findingsWe ascertained the toxicity of ELX-02 in cells and in mice as well as the effect of ELX-02 on translational read-through of nonsense mutations in cystinotic mice and human cells. ELX-02 was not toxic in vitro or in vivo, and permitted read-through of nonsense mutations in cystinotic mice and human cells.
conclusionsELX-02 has translational read-through activity and produces a functional CTNS protein, as evidenced by reduced cystine accumulation. This reduction is comparable to cysteamine treatment. ELX-02 accumulates in the kidney but neither cytotoxicity nor nephrotoxicity was observed.
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.