ArticleMolecular genetics and metabolism2014
Long-term nonsense suppression therapy moderates MPS I-H disease progression.
Article in Molecular genetics and metabolism, 2014. 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, 51 citations in OpenAlex.
- Translational readthrough therapy for ADPKD induces polycystin1 expression and partially rescues functional deficits in PKD1 mutant cells.Scientific reports · 2025Article
- Review
- Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules.Nature genetics · 2024Article
- Evaluation of Novel Enhancer Compounds in Gentamicin-Mediated Readthrough of Nonsense Mutations in Rett Syndrome.International journal of molecular sciences · 2023Article
- 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
- MPSI Manifestations and Treatment Outcome: Skeletal Focus.International journal of molecular sciences · 2022Review
- 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
- Ataluren suppresses a premature termination codon in an MPS I-H mouse.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Liver-directed gene therapy corrects neurologic disease in a murine model of mucopolysaccharidosis type I-Hurler.Molecular therapy. Methods & clinical development · 2022Article
- Stop Codon Context-Specific Induction of Translational Readthrough.Biomolecules · 2021Article
- Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement.Biomolecules · 2021Review
- Molecular Insights into Determinants of Translational Readthrough and Implications for Nonsense Suppression Approaches.International journal of molecular sciences · 2020Review
- Pseudouridine-mediated stop codon readthrough inRNA (New York, N.Y.) · 2020Article
- A regulated NMD mouse model supports NMD inhibition as a viable therapeutic option to treat genetic diseases.Disease models & mechanisms · 2020Article
- Mucopolysaccharidosis Type I.Diagnostics (Basel, Switzerland) · 2020Review
- Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia.Journal of clinical medicine · 2020Review
- Advances in therapeutic use of a drug-stimulated translational readthrough of premature termination codons.Molecular medicine (Cambridge, Mass.) · 2018Review
- Novel frameshift variant in the IDUA gene underlies Mucopolysaccharidoses type I in a consanguineous Yemeni pedigree.Molecular genetics and metabolism reports · 2017Article
- 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
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Nonsense suppression therapy is a therapeutic approach aimed at treating genetic diseases caused by in-frame premature termination codons (PTCs; also commonly known as nonsense mutations). This approach utilizes compounds that suppress translation termination at PTCs, which allows translation to continue and partial levels of deficient protein function to be restored. We hypothesize that suppression therapy can attenuate the lysosomal storage disease mucopolysaccharidosis type I-Hurler (MPS I-H), the severe form of α-L-iduronidase deficiency. α-L-iduronidase participates in glycosaminoglycan (GAG) catabolism and its insufficiency causes progressive GAG accumulation and onset of the MPS I-H phenotype, which consists of multiple somatic and neurological defects. 60-80% of MPS I-H patients carry a nonsense mutation in the IDUA gene. We previously showed that 2-week treatment with the designer aminoglycoside NB84 restored enough α-L-iduronidase function via PTC suppression to reduce tissue GAG accumulation in the Idua(tm1Kmke) MPS I-H mouse model, which carries a PTC homologous to the human IDUA-W402X nonsense mutation. Here we report that long-term NB84 administration maintains α-L-iduronidase activity and GAG reduction in Idua(tm1Kmke) mice throughout a 28-week treatment period. An examination of more complex MPS I-H phenotypes in Idua(tm1Kmke) mice following 28-week NB84 treatment revealed significant moderation of the disease in multiple tissues, including the brain, heart and bone, that are resistant to current MPS I-H therapies. This study represents the first demonstration that long-term nonsense suppression therapy can moderate progression of a genetic disease.
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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.