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Drug discovery

Kill the messenger where it lives

Nature volume 488, pages 36–37 (2012)Cite this article

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A mutant repeating DNA sequence produces a toxic RNA molecule that causes the neuromuscular disorder myotonic dystrophy type 1. An ‘antisense’ therapy that targets this RNA in cell nuclei shows promise in mice. See Letter p.111

Myotonic dystrophy type 1 is a devastating inherited disorder for which effective treatments are lacking. It is characterized by myotonia (delayed relaxation of muscles after contraction), weakness, cardiac arrhythmias, diabetes and cognitive changes. Patients carry a mutant DMPK gene that contains a greatly expanded DNA repeat sequence within a non-coding region1,2,3. When the mutant gene is expressed, it yields a messenger RNA molecule that seems to be toxic to cells such as muscle fibres4 — which means that the inheritance of a single mutant copy of DMPK from either parent is sufficient to cause disease. On page 111 of this issue, Wheeler and colleagues5 describe the successful use of antisense oligonucleotides (synthetic RNA-like fragments that bind to a target RNA) to correct the molecular and physiological features of the disease in a mouse model.

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Figure 1: How to silence a toxic RNA.

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Authors and Affiliations

  1. Peter K. Todd is in the Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA.,

    Peter K. Todd

  2. Henry L. Paulson is in the Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA.,

    Henry L. Paulson

Authors
  1. Peter K. Todd
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  2. Henry L. Paulson
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Correspondence to Peter K. Todd or Henry L. Paulson.

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Todd, P., Paulson, H. Kill the messenger where it lives. Nature 488, 36–37 (2012). https://doi.org/10.1038/488036a

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