ArticlePloS one2011
Ex vivo treatment with a novel synthetic aminoglycoside NB54 in primary fibroblasts from Rett syndrome patients suppresses MECP2 nonsense mutations.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- Release factor 3 degradation enhances aminoglycoside-mediated translational readthrough at MECP2 nonsense mutations.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Recent advances in epigenetic therapeutics for Rett syndrome: from mechanisms to clinical trials.Frontiers in behavioral neuroscience · 2026Review
- Xist condensates: perspectives for therapeutic intervention.Genome biology · 2025Review
- Systematic and quantitative analysis of stop codon readthrough in Rett syndrome nonsense mutations.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Evaluation of Novel Enhancer Compounds in Gentamicin-Mediated Readthrough of Nonsense Mutations in Rett Syndrome.International journal of molecular sciences · 2023Article
- Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives.Frontiers in neuroscience · 2023Review
- Selective Xi reactivation and alternative methods to restore MECP2 function in Rett syndrome.Trends in genetics : TIG · 2022Review
- Alternative models for transgenerational epigenetic inheritance: Molecular psychiatry beyond mice and man.World journal of psychiatry · 2021Review
- A no-nonsense approach to hereditary kidney disease.Pediatric nephrology (Berlin, Germany) · 2020Review
- Pharmacological read-through of R294X Mecp2 in a novel mouse model of Rett syndrome.Human molecular genetics · 2020Article
- Drug Studies on Rett Syndrome: From Bench to Bedside.Journal of autism and developmental disorders · 2020Review
- Nonsense Suppression Therapy: New Hypothesis for the Treatment of Inherited Bone Marrow Failure Syndromes.International journal of molecular sciences · 2020Review
- Frontotemporal dementia non-sense mutation of progranulin rescued by aminoglycosides.Human molecular genetics · 2020Article
- Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia.Journal of clinical medicine · 2020Review
- Rett syndrome: insights into genetic, molecular and circuit mechanisms.Nature reviews. Neuroscience · 2018Review
- Advances in therapeutic use of a drug-stimulated translational readthrough of premature termination codons.Molecular medicine (Cambridge, Mass.) · 2018Review
- Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures.American journal of medical genetics. Part C, Seminars in medical genetics · 2017Review
- Clinical and biological progress over 50 years in Rett syndrome.Nature reviews. Neurology · 2017Review
- Nonsense Suppression as an Approach to Treat Lysosomal Storage Diseases.Diseases (Basel, Switzerland) · 2016Article
- A flow cytometry-based reporter assay identifies macrolide antibiotics as nonsense mutation read-through agents.Journal of molecular medicine (Berlin, Germany) · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNonsense mutations in the X-linked methyl CpG-binding protein 2 (MECP2) comprise a significant proportion of causative MECP2 mutations in Rett syndrome (RTT). Naturally occurring aminoglycosides, such as gentamicin, have been shown to enable partial suppression of nonsense mutations related to several human genetic disorders, however, their clinical applicability has been compromised by parallel findings of severe toxic effects. Recently developed synthetic NB aminoglycosides have demonstrated significantly improved effects compared to gentamicin evident in substantially higher suppression and reduced acute toxicity in vitro.
resultsWe performed comparative study of suppression effects of the novel NB54 and gentamicin on three MECP2 nonsense mutations (R294X, R270X and R168X) common in RTT, using ex vivo treatment of primary fibroblasts from RTT patients harboring these mutations and testing for the C-terminal containing full-length MeCP2. We observed that NB54 induces dose-dependent suppression of MECP2 nonsense mutations more efficiently than gentamicin, which was evident at concentrations as low as 50 µg/ml. NB54 read-through activity was mutation specific, with maximal full-length MeCP2 recovery in R168X (38%), R270X (27%) and R294X (18%). In addition, the recovered MeCP2 was translocated to the cell nucleus and moreover led to parallel increase in one of the most important MeCP2 downstream effectors, the brain derived neurotrophic factor (BDNF).
conclusionOur findings suggest that NB54 may induce restoration of the potentially functional MeCP2 in primary RTT fibroblasts and encourage further studies of NB54 and other rationally designed aminoglycoside derivatives as potential therapeutic agents for nonsense MECP2 mutations in RTT.
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