ArticleMolecular genetics and metabolism2012
The designer aminoglycoside NB84 significantly reduces glycosaminoglycan accumulation associated with MPS I-H in the Idua-W392X mouse.
Article in Molecular genetics and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
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- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- Triamterene Functions as an Effective Nonsense Suppression Agent for MPS I-H (Hurler Syndrome).International journal of molecular sciences · 2023Article
- Ataluren suppresses a premature termination codon in an MPS I-H mouse.Journal of molecular medicine (Berlin, Germany) · 2022Article
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- Molecular Insights into Determinants of Translational Readthrough and Implications for Nonsense Suppression Approaches.International journal of molecular sciences · 2020Review
- A no-nonsense approach to hereditary kidney disease.Pediatric nephrology (Berlin, Germany) · 2020Review
- A regulated NMD mouse model supports NMD inhibition as a viable therapeutic option to treat genetic diseases.Disease models & mechanisms · 2020Article
- Drug Studies on Rett Syndrome: From Bench to Bedside.Journal of autism and developmental disorders · 2020Review
- 2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations.Nature communications · 2020Article
- Premature termination codon readthrough upregulates progranulin expression and improves lysosomal function in preclinical models of GRN deficiency.Molecular neurodegeneration · 2020Article
- Translational readthrough ofRNA biology · 2020Article
- Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia.Journal of clinical medicine · 2020Review
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges.Frontiers in molecular biosciences · 2020Review
- The aminoglycoside geneticin permits translational readthrough of the CTNS W138X nonsense mutation in fibroblasts from patients with nephropathic cystinosis.Pediatric nephrology (Berlin, Germany) · 2019Article
- Ribosomal mistranslation leads to silencing of the unfolded protein response and increased mitochondrial biogenesis.Communications biology · 2019Article
- Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations in mice.Nature biotechnology · 2018Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Suppression therapy utilizes compounds that suppress translation termination at in-frame premature termination codons (PTCs) to restore full-length, functional protein. This approach may provide a treatment for diseases caused by nonsense mutations such as mucopolysaccharidosis type I-Hurler (MPS I-H). MPS I-H is a lysosomal storage disease caused by severe α-L-iduronidase deficiency and subsequent lysosomal glycosaminoglycan (GAG) accumulation. MPS I-H represents a good target for suppression therapy because the majority of MPS I-H patients carry nonsense mutations, and restoration of even a small amount of functional α-L-iduronidase may attenuate the MPS I-H phenotype. In this study, we investigated the efficiency of suppression therapy agents to suppress the Idua-W392X nonsense mutation in an MPS I-H mouse model. The drugs tested included the conventional aminoglycosides gentamicin, G418, amikacin, and paromomycin. In addition, the designer aminoglycosides NB54 and NB84, two compounds previously designed to mediate efficient PTC suppression with reduced toxicity, were also examined. Overall, NB84 suppressed the Idua-W392X nonsense mutation much more efficiently than any of the other compounds tested. NB84 treatment restored enough functional α-L-iduronidase activity to partially reverse abnormal GAG accumulation and lysosomal abundance in mouse embryonic fibroblasts derived from the Idua-W392X mouse. Finally, in vivo administration of NB84 to Idua-W392X mice significantly reduced urine GAG excretion and tissue GAG storage. Together, these results suggest that NB84-mediated suppression therapy has the potential to attenuate the MPS I-H disease phenotype.
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