Spinal muscular atrophy (SMA), which results from the loss of expression of the survival of
motor neuron-1 (SMN1) gene, represents the most common genetic cause of pediatric
mortality. A duplicate copy (SMN2) is inefficiently spliced, producing a truncated and
unstable protein. We describe herein a potent, orally active, small-molecule enhancer of
SMN2 splicing that elevates full-length SMN protein and extends survival in a severe SMA
mouse model. We demonstrate that the molecular mechanism of action is via stabilization of …

Nat. Chem. Biol. 11, 141–147 (2015); published online 5 January 2015; corrected after print
15 July 2015 In the version of this article initially published, the zymosterol and zymostenol
structures shown in Figure 3a were depicted with a double bond at C14-C15, where there
should have been a single bond. The error has been corrected in the HTML and PDF
versions of the article.