Rho Kinase Inhibition with Fasudil in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis-Symptomatic Treatment Potential after Disease Onset

Research output: Contribution to journalResearch articleContributedpeer-review


  • René Günther - , Department of Neurology, University Medical Center Göttingen (Author)
  • Alexander Balck - , University of Lübeck (Author)
  • Jan C Koch - , University Medical Center Göttingen (Author)
  • Tobias Nientiedt - , Max Planck Institute of Experimental Medicine (Author)
  • Michael Sereda - , Max Planck Institute of Experimental Medicine (Author)
  • Mathias Bähr - , University Medical Center Göttingen (Author)
  • Paul Lingor - , University Medical Center Göttingen (Author)
  • Lars Tönges - , Ruhr University Bochum (Author)


Despite an improved understanding of the genetic background and the pathomechanisms of amyotrophic lateral sclerosis (ALS) no novel disease-modifying therapies have been successfully implemented in clinical routine. Riluzole still remains the only clinically approved substance in human ALS treatment with limited efficacy. We have previously identified pharmacological rho kinase (ROCK) inhibitors as orally applicable substances in SOD1.G93A transgenic ALS mice (SOD1G93A), which are able to extend survival time and improve motor function after presymptomatic treatment. Here, we have evaluated the therapeutic effect of the orally administered ROCK inhibitor Fasudil starting at a symptomatic disease stage, more realistically reflecting the clinical situation. Oral Fasudil treatment was initiated at a symptomatic stage at 80 days of life (d80) with 30 or 100 mg/kg body weight in both female and male mice. While baseline neurological scoring and survival were not influenced, Fasudil significantly improved motor behavior in male mice. Spinal cord pathology of motoneurons (MN) and infiltrating microglial cells (MG) at disease end-stage were not significantly modified. Although treatment after symptom onset was less potent than treatment in asymptomatic animals, our study shows the therapeutic benefits of this well-tolerated substance, which is already in clinical use for other indications.


Original languageEnglish
Pages (from-to)17
JournalFrontiers in pharmacology
Publication statusPublished - 2017

External IDs

PubMedCentral PMC5281550
Scopus 85012104120


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