These authors share last authorship.
A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation
Article first published online: 2 OCT 2012
Copyright © 2012 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 4, Issue 11, pages 1186–1199, November 2012
How to Cite
Goldmann, T., Overlack, N., Möller, F., Belakhov, V., van Wyk, M., Baasov, T., Wolfrum, U. and Nagel-Wolfrum, K. (2012), A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation. EMBO Mol Med, 4: 1186–1199. doi: 10.1002/emmm.201201438
- Issue published online: 2 NOV 2012
- Article first published online: 2 OCT 2012
- Manuscript Accepted: 22 AUG 2012
- Manuscript Revised: 17 AUG 2012
- Manuscript Received: 11 APR 2012
- Funded Access
- drug therapy;
- retinitis pigmentosa;
- sensoneuronal degeneration;
- Usher syndrome
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.