The Effects of Rufinamide on &amp;lt;i&amp;gt;in Vitro&amp;lt;/i&amp;gt; Spinal Muscular Atrophy Model

Shiori Ando,Hideaki Hideaki Hara,Kazuki Ohuchi,Michinori Funato,Shinsuke Nakamura,Masamitsu Shimazawa,Satoshi Inagaki,Arisu Sato,Hideo Kaneko

doi:10.4236/pp.2019.104014

The Effects of Rufinamide on &lt;i&gt;in Vitro&lt;/i&gt; Spinal Muscular Atrophy Model

Shiori Ando, Hideaki Hideaki Hara + Show 7 more

Open Access

https://doi.org/10.4236/pp.2019.104014

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Abstract

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.

Highlights

Spinal muscular atrophy (SMA) is autosomal recessive neurodegenerative disease characterized by progressive loss of motor neuron and skeletal muscle weakness [1]
SMA is caused by deletion or mutation of SMN1 gene and subsequent lack of SMN protein
SMN mRNA was significantly increased by addition of rufinamide in type III SMA patient-derived fibroblasts

Summary

Introduction

Spinal muscular atrophy (SMA) is autosomal recessive neurodegenerative disease characterized by progressive loss of motor neuron and skeletal muscle weakness [1]. SMA is caused by deletion or mutation of SMN1 SMN2 gene is highly homologous gene of SMN2 gene, but has a C to T transition compared to SMN1 gene [3]. This transition results in production of unstable form of SMN protein. Deletion and mutation of SMN1 gene cause a low expression level of SMN protein

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