Nature Communications (Jul 2021)

Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia

  • Masahiko Ajiro,
  • Tomonari Awaya,
  • Young Jin Kim,
  • Kei Iida,
  • Masatsugu Denawa,
  • Nobuo Tanaka,
  • Ryo Kurosawa,
  • Shingo Matsushima,
  • Saiko Shibata,
  • Tetsunori Sakamoto,
  • Rolenz Studer,
  • Adrian R. Krainer,
  • Masatoshi Hagiwara

DOI
https://doi.org/10.1038/s41467-021-24705-5
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 12

Abstract

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Familial dysautonomia is caused by splicing mutation of IKBKAP gene, which induces skipping of exon 20 and subsequent functional loss. Here, the authors report that a synthetic splice modulator RECTAS ameliorates pathogenic exon 20 skipping and shows therapeutic effects in cellular and animal models.