ArticlePloS one2015
Evaluation of Aminoglycoside and Non-Aminoglycoside Compounds for Stop-Codon Readthrough Therapy in Four Lysosomal Storage Diseases.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Recovery of α-L-fucosidase in fucosidosis nonsense variants by readthrough stimulation and release factor degradation.Disease models & mechanisms · 2026Article
- Review
- Amlexanox: Readthrough Induction and Nonsense-Mediated mRNA Decay Inhibition in a Charcot-Marie-Tooth Model of hiPSCs-Derived Neuronal Cells Harboring a Nonsense Mutation inPharmaceuticals (Basel, Switzerland) · 2023Article
- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- Emerging Personalized Opportunities for Enhancing Translational Readthrough in Rare Genetic Diseases and Beyond.International journal of molecular sciences · 2023Review
- Gene Therapy of Sphingolipid Metabolic Disorders.International journal of molecular sciences · 2023Review
- 2-Guanidino-quinazoline promotes the readthrough of nonsense mutations underlying human genetic diseases.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT.The Journal of experimental medicine · 2022Article
- Mucopolysaccharidosis Type VI, an Updated Overview of the Disease.International journal of molecular sciences · 2021Review
- Novel therapies for mucopolysaccharidosis type III.Journal of inherited metabolic disease · 2021Review
- A no-nonsense approach to hereditary kidney disease.Pediatric nephrology (Berlin, Germany) · 2020Review
- Translational readthrough ofRNA biology · 2020Article
- Absence of p.R50XDisease models & mechanisms · 2020Article
- Serum starvation enhances nonsense mutation readthrough.Journal of molecular medicine (Berlin, Germany) · 2019Article
- 2-Aminothiazole-4-carboxamides Enhance Readthrough of Premature Termination Codons by Aminoglycosides.ACS medicinal chemistry letters · 2019Article
- Lysosomal diseases: Overview on current diagnosis and treatment.Genetics and molecular biology · 2019Article
- The effect of PTC124 on choroideremia fibroblasts and iPSC-derived RPE raises considerations for therapy.Scientific reports · 2018Article
- Advances in therapeutic use of a drug-stimulated translational readthrough of premature termination codons.Molecular medicine (Cambridge, Mass.) · 2018Review
- How close are we to therapies for Sanfilippo disease?Metabolic brain disease · 2018Review
- Small molecules as therapeutic agents for inborn errors of metabolism.Journal of inherited metabolic disease · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonsense mutations are quite prevalent in inherited diseases. Readthrough drugs could provide a therapeutic option for any disease caused by this type of mutation. Geneticin (G418) and gentamicin were among the first to be described. Novel compounds have been generated, but only a few have shown improved results. PTC124 is the only compound to have reached clinical trials. Here we first investigated the readthrough effects of gentamicin on fibroblasts from one patient with Sanfilippo B, one with Sanfilippo C, and one with Maroteaux-Lamy. We found that ARSB activity (Maroteaux-Lamy case) resulted in an increase of 2-3 folds and that the amount of this enzyme within the lysosomes was also increased, after treatment. Since the other two cases (Sanfilippo B and Sanfilippo C) did not respond to gentamicin, the treatments were extended with the use of geneticin and five non-aminoglycoside (PTC124, RTC13, RTC14, BZ6 and BZ16) readthrough compounds (RTCs). No recovery was observed at the enzyme activity level. However, mRNA recovery was observed in both cases, nearly a two-fold increase for Sanfilippo B fibroblasts with G418 and around 1.5 fold increase for Sanfilippo C cells with RTC14 and PTC124. Afterwards, some of the products were assessed through in vitro analyses for seven mutations in genes responsible for those diseases and, also, for Niemann-Pick A/B. Using the coupled transcription/translation system (TNT), the best results were obtained for SMPD1 mutations with G418, reaching a 35% recovery at 0.25 μg/ml, for the p.W168X mutation. The use of COS cells transfected with mutant cDNAs gave positive results for most of the mutations with some of the drugs, although to a different extent. The higher enzyme activity recovery, of around two-fold increase, was found for gentamicin on the ARSB p.W146X mutation. Our results are promising and consistent with those of other groups. Further studies of novel compounds are necessary to find those with more consistent efficacy and fewer toxic effects.
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