TITLE:
The Effects of Rufinamide on in Vitro Spinal Muscular Atrophy Model
AUTHORS:
Shiori Ando, Arisu Sato, Michinori Funato, Kazuki Ohuchi, Satoshi Inagaki, Shinsuke Nakamura, Masamitsu Shimazawa, Hideo Kaneko, Hideaki Hideaki Hara
KEYWORDS:
Spinal Muscular Atrophy, Rufinamide, iPSCs
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.10 No.4,
April
15,
2019
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.