ArticleMolecular genetics and metabolism2011
Stop codon read-through with PTC124 induces palmitoyl-protein thioesterase-1 activity, reduces thioester load and suppresses apoptosis in cultured cells from INCL patients.
Article in Molecular genetics and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Circulating Truncated Alpha-1 Antitrypsin Glycoprotein in Patient Plasma Retains Anti-Inflammatory Capacity.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Ataluren treatment of patients with nonsense mutation dystrophinopathy.Muscle & nerve · 2014Trial
- Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy.PloS one · 2013Trial
- Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules.Nature genetics · 2024Article
- Ataluren-Promising Therapeutic Premature Termination Codon Readthrough Frontrunner.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Human INCL fibroblasts display abnormal mitochondrial and lysosomal networks and heightened susceptibility to ROS-induced cell death.PloS one · 2021Article
- Serum starvation enhances nonsense mutation readthrough.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Caffeine boosts Ataluren's readthrough activity.Heliyon · 2019Article
- Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses.Molecular neurodegeneration · 2019Review
- Advances in therapeutic use of a drug-stimulated translational readthrough of premature termination codons.Molecular medicine (Cambridge, Mass.) · 2018Review
- Optimized approach for the identification of highly efficient correctors of nonsense mutations in human diseases.PloS one · 2017Article
- Nonsense Suppression as an Approach to Treat Lysosomal Storage Diseases.Diseases (Basel, Switzerland) · 2016Article
- Progress in the Development of Small Molecule Therapeutics for the Treatment of Neuronal Ceroid Lipofuscinoses (NCLs).Journal of medicinal chemistry · 2016Review
- Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis.Orphanet journal of rare diseases · 2016Review
- A flow cytometry-based reporter assay identifies macrolide antibiotics as nonsense mutation read-through agents.Journal of molecular medicine (Berlin, Germany) · 2016Article
- Clinical potential of ataluren in the treatment of Duchenne muscular dystrophy.Degenerative neurological and neuromuscular disease · 2016Review
- Reversible Cysteine Acylation Regulates the Activity of Human Palmitoyl-Protein Thioesterase 1 (PPT1).PloS one · 2016Article
- Effect of Readthrough Treatment in Fibroblasts of Patients Affected by Lysosomal Diseases Caused by Premature Termination Codons.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Article
- The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy.Human molecular genetics · 2015Article
- Mice homozygous for c.451C>T mutation in Cln1 gene recapitulate INCL phenotype.Annals of clinical and translational neurology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Infantile neuronal ceroid lipofuscinosis (INCL), a lethal hereditary neurodegenerative lysosomal storage disorder, affects mostly children. It is caused by inactivating mutations in the palmitoyl-protein thioesterase-1(PPT1) gene. Nonsense mutations in a gene generate premature termination codons producing truncated,nonfunctional or deleterious proteins. PPT1 nonsense-mutations account for approximately 31% of INCL patients in the US. Currently, there is no effective treatment for this disease. While aminoglycosides such asgentamycin suppress nonsense mutations, inherent toxicity of aminoglycosides prohibits chronic use inpatients. PTC124 is a non-toxic compound that induces ribosomal read-through of premature termination codons. We sought to determine whether PTC124-treatment of cultured cells from INCL patients carrying nonsense mutations in the PPT1 gene would correct PPT1 enzyme-deficiency with beneficial effects. Our results showed that PTC124-treatment of cultured cells from INCL patients carrying PPT1 nonsense-mutations induced PPT1 enzymatic activity in a dose- and time-dependent manner. This low level of PPT1 enzyme activity induced by PTC124 is virtually identical to that induced by gentamycin-treatment. Even though only a modest increase in PPT1 activity was achieved by PTC124-treatment of INCL cells, this treatment reduced the levels of thioester (constituent of ceroid) load. Our results suggest that PTC124-treatment induces PPT1 enzymatic activity in cultured cells from INCL patients carrying PPT1 nonsense-mutations, and this modest enzymatic activity has demonstrable beneficial effects on these cells. The clinical relevance of these effects may be tested in animal models of INCL carrying nonsense mutations in the PPT1 gene.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.