The Effects of Rufinamide on <i>in Vitro</i>Spinal Muscular Atrophy Model

• 作者: Arisu Sato Hideaki Hideaki Hara Hideo Kaneko Kazuki Ohuchi Masamitsu Shimazawa Michinori Funato Satoshi Inagaki Shinsuke Nakamura Shiori Ando
• 来源期刊: 药理与制药(英文)
• 学科: 医学
• 关键词: Spinal MUSCULAR ATROPHY RUFINAMIDE IPSCS
• 年，卷（期）: 2019,（4）
• 页码范围: 159-168
• 页数: 10页
• 分类号: R73

摘要

Spinal muscular atrophy (SMA) is devastating genetic disease characterized by progressive loss of motor neuron and skeletal muscle weakness. SMA is the most common lethal genetic disease in infancy. SMA is caused by deletion or mutation of SMN1 gene and subsequent lack of SMN protein. Our purpose in this study was to evaluate the therapeutic potential of rufinamide, an antiepileptic drug. In this study, SMA patient-derived fibroblasts and differentiated spinal motor neurons (MNs) using SMA patient-derived iPSCs were used as in vitro SMA model. SMN mRNA was significantly increased by addition of rufinamide in type III SMA patient-derived fibroblasts. Furthermore, rufinamide stimulated neurite elongation in type III SMA patient derived-iPSCs-MNs. In contrast of the result using type III SMA patient-derived fibroblasts, the expression level of SMN mRNA was not changed after rufinamide treatment in type I SMA patient-derived fibroblasts, and rufinamide did not affect neurite outgrowth in type I SMA patients derived-iPSCs-MNs. These findings indicate that rufinamide may be one of the potential candidate drugs for mild type of SMA.