神経治療学
Online ISSN : 2189-7824
Print ISSN : 0916-8443
ISSN-L : 2189-7824
教育講演
脊髄性筋萎縮症に対する神経スプライシング制御治療
佐橋 健太郎勝野 雅央
著者情報
ジャーナル フリー

2020 年 37 巻 3 号 p. 247-250

詳細
抄録

Loss–of–function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. Humans have a closely related SMN2, but it only expresses low levels of SMN protein, due to alternative splicing of exon 7. Antisense oligonucleotides (ASOs) can be designed to regulate splicing of target pre–mRNAs. Based on an ASO–tiling method, we succeeded in identifying an optimized 2′–MOE phosphorothioate ASO that efficiently redirects SMN2 splicing. Its therapeutic efficacy, safety, and pharmacokinetics were proven in preclinical studies using mice and NHPs and further supported by clinical trials in SMA infants and children. Exploring of the in vivo spatial and temporal ASO effects yields insights into SMN roles in SMA pathogenesis, which in turn contributes to the successful development of targeted therapeutics.

著者関連情報
© 2020 日本神経治療学会
前の記事 次の記事
feedback
Top