The Protective Effects of Levetiracetam on a Human iPSCs-Derived Spinal Muscular Atrophy Model

  • Shiori Ando
  • Michinori Funato
  • Kazuki Ohuchi
  • Satoshi Inagaki
  • Arisu Sato
  • Junko Seki
  • Chizuru Kawase
  • Toshio Saito
  • Hisahide Nishio
  • Shinsuke Nakamura
  • Masamitsu Shimazawa
  • Hideo Kaneko
  • Hideaki HaraEmail author
Original Paper


Spinal muscular atrophy (SMA) is an inherited disease characterized by progressive motor neuron death and subsequent muscle weakness and is caused by deletion or mutation of survival motor neuron (SMN) 1 gene. Protecting spinal motor neuron is an effective clinical strategy for SMA. The purpose of this study was to investigate the potential effect of an anti-epileptic drug levetiracetam on SMA. In the present study, we used differentiated spinal motor neurons (MNs) from SMA patient-derived induced pluripotent stem cells (SMA-iPSCs) to investigate the effect of levetiracetam. Levetiracetam promoted neurite elongation in SMA-iPSCs-MNs. TUNEL-positive spinal motor neurons were significantly reduced by levetiracetam in SMA-iPSCs-MNs. In addition, the expression level of cleaved-caspase 3 was decreased by levetiracetam in SMA-iPSCs-MNs. Furthermore, levetiracetam improved impaired mitochondrial function in SMA-iPSCs-MNs. On the other hand, levetiracetam did not affect the expression level of SMN protein in SMA-iPSCs-MNs. These findings indicate that levetiracetam has a neuroprotective effect for SMA.


Spinal muscular atrophy Induced pluripotent stem cells Levetiracetam Motor neuron 



We greatly appreciate the patients and their family who cooperated with this study. We thank Prof. Kenji Osafune (Kyoto University) for providing the human iPSC line 201B7. This study was supported in part by Health and Labor Sciences Research Grants of Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare (H26-itaku(nan)-ippan-059).

Compliance with Ethical Standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethics Statement

The procedures used in the experiments on human induced pluripotent stem cells (Control iPSCs; 201B7 line) adhered to the tenets of the Declaration of Helsinki. The 201B7 line was generated from adult human dermal fibroblasts which was purchased from Cell Applications, Inc (San Diego, CA, USA) [36]. The somatic cells collection from the patients, the establishment of patient-derived iPSCs, and pathological analysis of differentiated iPSCs including evaluation of the potential drug efficacy were planned in this study. These planed protocols were approved by the Ethics Review Committee of the National Hospital Organization, Nagara Medical Center (Approval Number: 26-15), and informed consents were obtained from the parents of our pediatric patients. Informed consents were obtained from the subjects after explanation of the nature and possible consequences of the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Shiori Ando
    • 1
    • 2
  • Michinori Funato
    • 2
  • Kazuki Ohuchi
    • 1
    • 2
  • Satoshi Inagaki
    • 1
    • 2
  • Arisu Sato
    • 1
    • 2
  • Junko Seki
    • 2
  • Chizuru Kawase
    • 2
  • Toshio Saito
    • 3
  • Hisahide Nishio
    • 4
  • Shinsuke Nakamura
    • 1
  • Masamitsu Shimazawa
    • 1
  • Hideo Kaneko
    • 2
  • Hideaki Hara
    • 1
    Email author
  1. 1.Molecular Pharmacology, Department of Biofunctional EvaluationGifu Pharmaceutical UniversityGifuJapan
  2. 2.Department of Clinical Research, National Hospital OrganizationNagara Medical CenterGifuJapan
  3. 3.Division of Child Neurology, Department of NeurologyNational Hospital Organization, Toneyama National HospitalToyonakaJapan
  4. 4.Department of Occupational Therapy, Faculty of RehabilitationKobe Gakuin UniversityKobeJapan

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