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Rescue of nonsense mutations by amlexanox in human cells

Sara Gonzalez-Hilarion11323, Terence Beghyn3456, Jieshuang Jia123, Nadège Debreuck3, Gonzague Berte3456, Kamel Mamchaoui10789, Vincent Mouly10789, Dieter C Gruenert1112, Benoit Déprez3456 and Fabrice Lejeune123*

Author Affiliations

1 Université Lille Nord de France, IFR142, Lille, France

2 Inserm, Equipe AVENIR, Lille, France

3 Institut Pasteur de Lille, Lille, France

4 INSERM U761 Biostructures and Drug Discovery, Lille, F-59000, France

5 Faculté de Pharmacie, Université Lille Nord de France, F-59000, Lille, France

6 PRIM (, F-59000, Lille, France

7 Institut de Myologie, UM76, Paris, France

8 Université Pierre et Marie Curie, Faculté de Médecine Pierre et Marie Curie, Paris, France

9 Inserm, UMRS 974, Paris, France

10 CNRS, UMR, 7215, Paris, France

11 Departments of Otolaryngology-Head and Neck Surgery and of Laboratory Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Helen Diller Family Comprehensive Cancer Center, Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA

12 Department of Pediatrics, University of Vermont College of Medicine, Burlington, VT, USA

13 Present address: Unité des Aspergillus, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France

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Orphanet Journal of Rare Diseases 2012, 7:58  doi:10.1186/1750-1172-7-58

Published: 31 August 2012



Nonsense mutations are at the origin of many cancers and inherited genetic diseases. The consequence of nonsense mutations is often the absence of mutant gene expression due to the activation of an mRNA surveillance mechanism called nonsense-mediated mRNA decay (NMD). Strategies to rescue the expression of nonsense-containing mRNAs have been developed such as NMD inhibition or nonsense mutation readthrough.


Using a dedicated screening system, we sought molecules capable to block NMD. Additionally, 3 cell lines derived from patient cells and harboring a nonsense mutation were used to study the effect of the selected molecule on the level of nonsense-containing mRNAs and the synthesis of proteins from these mutant mRNAs.


We demonstrate here that amlexanox, a drug used for decades, not only induces an increase in nonsense-containing mRNAs amount in treated cells, but also leads to the synthesis of the full-length protein in an efficient manner. We also demonstrated that these full length proteins are functional.


As a result of this dual activity, amlexanox may be useful as a therapeutic approach for diseases caused by nonsense mutations.

NMD/nonsense mutation/readthrough/RNA/small molecules