A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Tobias Goldmann
  • Nora Overlack
  • Fabian Möller
  • Valery Belakhov
  • Michiel Van Wyk
  • Timor Baasov
  • Uwe Wolfrum
  • Kerstin Nagel-Wolfrum
Sammlungen
  • metadata
ISSN
1757-4684
Ausgabe der Veröffentlichung
11
Zeitschrift
EMBO molecular medicine
Schlüsselwörter
  • 570 Biowissenschaften
  • 570 Life sciences
Sprache
eng
Paginierung
Seiten: 1186 - 1199
Datum der Veröffentlichung
2012
Herausgeber
Wiley-VCH
Herausgeber URL
http://dx.doi.org/10.1002/emmm.201201438
Datum der Datenerfassung
2020
Datum, an dem der Datensatz öffentlich gemacht wurde
2020
Zugang
Public
Titel
A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation
Ausgabe der Zeitschrift
4

Datenquelle: METADATA.UB

Andere Metadatenquellen:
Autoren
  • Tobias Goldmann
  • Nora Overlack
  • Fabian Moeller
  • Valery Belakhov
  • Michiel van Wyk
  • Timor Baasov
  • Uwe Wolfrum
  • Kerstin Nagel-Wolfrum
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000310599100005&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1002/emmm.201201438
eISSN
1757-4684
Externe Identifier
  • Clarivate Analytics Document Solution ID: 030VV
  • PubMed Identifier: 23027640
ISSN
1757-4676
Ausgabe der Veröffentlichung
11
Zeitschrift
EMBO MOLECULAR MEDICINE
Schlüsselwörter
  • drug therapy
  • pharmacogenetics
  • retinitis pigmentosa
  • sensoneuronal degeneration
  • Usher syndrome
Paginierung
1186 - 1199
Datum der Veröffentlichung
2012
Status
Published
Titel
A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an <i>USH1C</i> nonsense mutation
Sub types
  • Article
Ausgabe der Zeitschrift
4

Datenquelle: Web of Science (Lite)

Abstract
<jats:title>Abstract</jats:title><jats:p>Translational read‐through‐inducing drugs (TRIDs) promote read‐through of nonsense mutations, placing them in the spotlight of current gene‐based therapeutic research. Here, we compare for the first time the relative efficacies of new‐generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read‐through efficacy of a nonsense mutation in the <jats:italic>USH1C</jats:italic> gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf‐blindness. We quantify read‐through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read‐through efficacy of the TRIDs in retinal cultures; however, we show an excellent biocompatibility in retinal cultures with read‐through <jats:italic>versus</jats:italic> toxicity evidently superior for NB54 and PTC124. In addition, <jats:italic>in vivo</jats:italic> administration of NB54 and PTC124 induced recovery of the full‐length harmonin a1 with the same efficacy. The high biocompatibilities combined with the sustained read‐through efficacies of these drugs emphasize the potential of NB54 and PTC124 in treating nonsense mutation‐based retinal disorders.</jats:p>
Autoren
  • Tobias Goldmann
  • Nora Overlack
  • Fabian Möller
  • Valery Belakhov
  • Michiel van Wyk
  • Timor Baasov
  • Uwe Wolfrum
  • Kerstin Nagel‐Wolfrum
DOI
10.1002/emmm.201201438
eISSN
1757-4684
ISSN
1757-4676
Ausgabe der Veröffentlichung
11
Zeitschrift
EMBO Molecular Medicine
Sprache
en
Online publication date
2012
Paginierung
1186 - 1199
Datum der Veröffentlichung
2012
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1002/emmm.201201438
Datum der Datenerfassung
2023
Titel
A comparative evaluation of NB30, NB54 and PTC124 in translational read‐through efficacy for treatment of an <i>USH1C</i> nonsense mutation
Ausgabe der Zeitschrift
4

Datenquelle: Crossref

Abstract
Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read-through efficacy of a nonsense mutation in the USH1C gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf-blindness. We quantify read-through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read-through efficacy of the TRIDs in retinal cultures; however, we show an excellent biocompatibility in retinal cultures with read-through versus toxicity evidently superior for NB54 and PTC124. In addition, in vivo administration of NB54 and PTC124 induced recovery of the full-length harmonin a1 with the same efficacy. The high biocompatibilities combined with the sustained read-through efficacies of these drugs emphasize the potential of NB54 and PTC124 in treating nonsense mutation-based retinal disorders.
Addresses
  • Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University of Mainz, Germany.
Autoren
  • Tobias Goldmann
  • Nora Overlack
  • Fabian Möller
  • Valery Belakhov
  • Michiel van Wyk
  • Timor Baasov
  • Uwe Wolfrum
  • Kerstin Nagel-Wolfrum
DOI
10.1002/emmm.201201438
eISSN
1757-4684
Externe Identifier
  • PubMed Identifier: 23027640
  • PubMed Central ID: PMC3494875
Open access
true
ISSN
1757-4676
Ausgabe der Veröffentlichung
11
Zeitschrift
EMBO molecular medicine
Schlüsselwörter
  • Retina
  • Cell Line
  • Animals
  • Mice, Inbred C57BL
  • Humans
  • Mice
  • Retinal Diseases
  • Oxadiazoles
  • Aminoglycosides
  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Codon, Nonsense
  • Peptide Chain Elongation, Translational
  • Female
  • Male
  • In Vitro Techniques
Sprache
eng
Medium
Print-Electronic
Online publication date
2012
Open access status
Open Access
Paginierung
1186 - 1199
Datum der Veröffentlichung
2012
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2012
Titel
A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation.
Sub types
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
4

Files

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/emmm.201201438 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23027640/pdf/?tool=EBI https://europepmc.org/articles/PMC3494875?pdf=render

Datenquelle: Europe PubMed Central

Abstract
Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read-through efficacy of a nonsense mutation in the USH1C gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf-blindness. We quantify read-through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read-through efficacy of the TRIDs in retinal cultures; however, we show an excellent biocompatibility in retinal cultures with read-through versus toxicity evidently superior for NB54 and PTC124. In addition, in vivo administration of NB54 and PTC124 induced recovery of the full-length harmonin a1 with the same efficacy. The high biocompatibilities combined with the sustained read-through efficacies of these drugs emphasize the potential of NB54 and PTC124 in treating nonsense mutation-based retinal disorders.
Date of acceptance
2012
Autoren
  • Tobias Goldmann
  • Nora Overlack
  • Fabian Möller
  • Valery Belakhov
  • Michiel van Wyk
  • Timor Baasov
  • Uwe Wolfrum
  • Kerstin Nagel-Wolfrum
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/23027640
DOI
10.1002/emmm.201201438
eISSN
1757-4684
Externe Identifier
  • PubMed Central ID: PMC3494875
Ausgabe der Veröffentlichung
11
Zeitschrift
EMBO Mol Med
Schlüsselwörter
  • Adaptor Proteins, Signal Transducing
  • Aminoglycosides
  • Animals
  • Cell Cycle Proteins
  • Cell Line
  • Codon, Nonsense
  • Cytoskeletal Proteins
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxadiazoles
  • Peptide Chain Elongation, Translational
  • Retina
  • Retinal Diseases
Sprache
eng
Country
England
Paginierung
1186 - 1199
Datum der Veröffentlichung
2012
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2013
Titel
A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation.
Sub types
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
4

Datenquelle: PubMed

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