臨床神経学

<シンポジウム05―1>筋ジストロフィー新規治療法開発の最前線

デュシェンヌ型に対するエクソン・スキップ治療

武田 伸一

国立精神・神経センタートランスレーショナル・メディカルセンター
神経研究所遺伝子疾患治療研究部〔〒187―8502 東京都小平市小川東町4―1―1〕

Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin at the sarcolemma. Exon skipping by antisense oligonucleotides is a novel method to restore the reading frame of the mutated DMD gene, and rescue dystrophin expression. We recently reported that systemic delivery of Morpholino antisense oligonucleotides targeting exon 6 and 8 of the canine DMD gene, efficiently recovered functional dystrophin at the sarcolamma of dystrophic dogs, and improved phenotypes of affected dogs without serious side effects (Ann Neurol. 65: 667-676, 2009). To optimize therapeutic antisense Morpholinos for more frequent mutations of the DMD gene, we designed antisense Morpholinos targeting exon 51 of the mouse DMD gene, and injected them separately or in combination into the muscles of mdx52 mice, in which exon 52 has been deleted by a gene targeting technique. We also tried systemic delivery of antisense Morpholino to skip exon 51 in mdx 52 mice and found the amelioration of the phenotypes (Mol Ther, 2010). Clinical trials of exon 51 skipping for DMD patients is now going in our country and application of antisense strategy to other hereditary neuromuscular diseases is largely expected.
Full Text of this Article in Japanese PDF (212K)

(臨床神経, 51:914−916, 2011)
key words:Duchenne型筋ジストロフィー,ジストロフィン,エクソン・スキッピング,mdx52マウス,臨床治験

(受付日:2011年5月19日)