Sense from nonsense: therapies for premature stop codon diseases.

Laure Bidou, Valérie Allamand, Jean-Pierre Rousset, Olivier Namy

Université Paris-Sud, Orsay, France.

Trends in molecular medicine 2012 Nov

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Ten percent of inherited diseases are caused by premature termination codon (PTC) mutations that lead to degradation of the mRNA template and to the production of a non-functional, truncated polypeptide. In addition, many acquired mutations in cancer introduce similar PTCs. In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC. Since, many studies have validated this approach, but despite the promise of PTC readthrough therapies, the mechanisms of translation termination remain to be precisely elucidated before even more progress can be made. Here, we review the molecular basis for PTC readthrough in eukaryotes and describe currently available compounds with significant therapeutic potential for treating genetic disorders and cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Laure Bidou, Valérie Allamand, Jean-Pierre Rousset, Olivier Namy. Sense from nonsense: therapies for premature stop codon diseases. Trends in molecular medicine. 2012 Nov;18(11):679-88