シンポジウム7：難治性神経筋疾患で始まった核酸医薬による原因治療
脊髄性筋萎縮症に対するアンチセンス核酸治療
キーワード:
spinal muscular atrophy,
SMN gene,
antisense therapy,
intrathecal administration,
exon inclusion
2019 年 36 巻 3 号 p. 311-316
詳細
2019 年 36 巻 3 号 p. 311-316
In July 2017, a nucleic acid agent (drug name : Nusinersen) for patients with spinal muscular atrophy (SMA) obtained manufacturing approval in Japan. The functional full length survival motor neuron (SMN) protein is only minimally produced by the SMN2 gene in patients with SMA. The mechanism of action of Nusinersen involves binding to the hnRNP–A1/A2–dependent splicing silencer region in the pre–mRNA of SMN, which is responsible for impaired binding of hnRNP–A1/A2 to the SMN pre–mRNA, and inclusion of exon 7. The full–length SMN protein is synthesized due to this exon inclusion. At present, new SMA treatments are under development. These novel approaches include intrathecal administration of nucleic acid agents, oral administration of small molecules, and gene therapy using viral vectors. The effectiveness and safety of these treatments are being evaluated by international joint clinical trials. Early diagnosis and intervention at an early disease stage by genetic testing have become important at medical sites worldwide, in anticipation of slowing or even halting the symptoms of SMA as well as preventing the onset of this disease.
