ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2015
Effect of Readthrough Treatment in Fibroblasts of Patients Affected by Lysosomal Diseases Caused by Premature Termination Codons.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 22 citations in OpenAlex.
- Precision therapeutic tRNA rescue of nonsense mutation R166X inJournal of precision medicine (Amsterdam, Netherlands) · 2025Article
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- Enzyme Replacement Therapy for FABRY Disease: Possible Strategies to Improve Its Efficacy.International journal of molecular sciences · 2023Article
- The Usher syndrome 1C protein harmonin regulates canonical Wnt signaling.Frontiers in cell and developmental biology · 2023Article
- Stop Codon Context-Specific Induction of Translational Readthrough.Biomolecules · 2021Article
- Molecular Insights into Determinants of Translational Readthrough and Implications for Nonsense Suppression Approaches.International journal of molecular sciences · 2020Review
- Translational readthrough ofRNA biology · 2020Article
- Ataluren for the Treatment of Usher Syndrome 2A Caused by Nonsense Mutations.International journal of molecular sciences · 2019Article
- Serum starvation enhances nonsense mutation readthrough.Journal of molecular medicine (Berlin, Germany) · 2019Article
- A breakthrough in readthrough? Could geneticin lead the way to effective treatment for cystinosis nonsense mutations?Pediatric nephrology (Berlin, Germany) · 2019Article
- The effect of PTC124 on choroideremia fibroblasts and iPSC-derived RPE raises considerations for therapy.Scientific reports · 2018Article
- Small molecules as therapeutic agents for inborn errors of metabolism.Journal of inherited metabolic disease · 2017Review
- A flow cytometry-based reporter assay identifies macrolide antibiotics as nonsense mutation read-through agents.Journal of molecular medicine (Berlin, Germany) · 2016Article
- Article
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8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aminoglycoside antibiotics, such as gentamicin, may induce premature termination codon (PTC) readthrough and elude the nonsense-mediated mRNA decay mechanism. Because PTCs are frequently involved in lysosomal diseases, readthrough compounds may be useful as potential therapeutic agents. The aim of our study was to identify patients responsive to gentamicin treatment in order to be used as positive controls to further screen for other PTC readthrough compounds. With this aim, fibroblasts from 11 patients affected by 6 different lysosomal diseases carrying PTCs were treated with gentamicin. Treatment response was evaluated by measuring enzymatic activity, abnormal metabolite accumulation, mRNA expression, protein localization, and cell viability. The potential effect of readthrough was also analyzed by in silico predictions. Results showed that fibroblasts from 5/11 patients exhibited an up to 3-fold increase of enzymatic activity after gentamicin treatment. Accordingly, cell lines tested showed enhanced well-localized protein and/or increased mRNA expression levels and/or reduced metabolite accumulation. Interestingly, these cell lines also showed increased enzymatic activity after PTC124 treatment, which is a PTC readthrough-promoting compound. In conclusion, our results provide a proof-of-concept that PTCs can be effectively suppressed by readthrough drugs, with different efficiencies depending on the genetic context. The screening of new compounds with readthrough activity is a strategy that can be used to develop efficient therapies for diseases caused by PTC mutations.
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