ArticleScientific reports2018
The effect of PTC124 on choroideremia fibroblasts and iPSC-derived RPE raises considerations for therapy.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Restoration of functional PAX6 in aniridia patient iPSC-derived ocular tissue models using repurposed nonsense suppression drugs.Molecular therapy. Nucleic acids · 2023Article
- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- Recoding of Nonsense Mutation as a Pharmacological Strategy.Biomedicines · 2023Review
- Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis.Stem cell reports · 2022Article
- Molecular Therapy for Choroideremia: Pre-clinical and Clinical Progress to Date.Molecular diagnosis & therapy · 2021Article
- Stop Codon Context-Specific Induction of Translational Readthrough.Biomolecules · 2021Article
- REP1 deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia.JCI insight · 2021Article
- Nonsense suppression therapies in human genetic diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Update on Gene Therapy Clinical Trials for Choroideremia and Potential Experimental Therapies.Medicina (Kaunas, Lithuania) · 2021Review
- Is subretinal AAV gene replacement still the only viable treatment option for choroideremia?Expert opinion on orphan drugs · 2021Article
- Design of efficacious somatic cell genome editing strategies for recessive and polygenic diseases.Nature communications · 2020Article
- In vitro metabolism, reaction phenotyping, enzyme kinetics, CYP inhibition and induction potential of ataluren.Pharmacology research & perspectives · 2020Article
- Molecular Therapies for Choroideremia.Genes · 2019Review
- Article
- Molecular Therapies for Inherited Retinal Diseases-Current Standing, Opportunities and Challenges.Genes · 2019Review
- Nonsense-mediated mRNA decay efficiency varies in choroideremia providing a target to boost small molecule therapeutics.Human molecular genetics · 2019Article
- Novel CHM mutations in Polish patients with choroideremia - an orphan disease with close perspective of treatment.Orphanet journal of rare diseases · 2018Article
- Choroideremia: from genetic and clinical phenotyping to gene therapy and future treatments.Therapeutic advances in ophthalmologyReview
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inherited retinal dystrophies (IRDs) are caused by mutations in over 200 genes, resulting in a range of therapeutic options. Translational read-through inducing drugs (TRIDs) offer the possibility of treating multiple IRDs regardless of the causative gene. TRIDs promote ribosomal misreading of premature stop codons, which results in the incorporation of a near-cognate amino acid to produce a full-length protein. The IRD choroideremia (CHM) is a pertinent candidate for TRID therapy, as nonsense variants cause 30% of cases. Recently, treatment of the UAA nonsense-carrying CHM zebrafish model with the TRID PTC124 corrected the underlying biochemical defect and improved retinal phenotype. To be clinically relevant, we studied PTC124 efficiency in UAA nonsense-carrying human fibroblasts and induced pluripotent stem cell-derived retinal pigment epithelium, as well as in a UAA-mutated CHM overexpression system. We showed that PTC124 treatment induces a non-significant trend for functional rescue, which could not be improved by nonsense-mediated decay inhibition. Furthermore, it does not produce a detectable CHM-encoded protein even when coupled with a proteasome inhibitor. We suggest that drug efficiency may depend upon on the target amino acid and its evolutionary conservation, and argue that patient cells should be screened in vitro prior to inclusion in a clinical trial.
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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.