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Cited by 47Amyotrophic Lateral Sclerosis ResearchNeurogenetic and Muscular Disorders ResearchAlzheimer's disease research and treatments

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

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Günther, René, Balck, Alexander, Koch, Jan C., Nientiedt, Tobias, Sereda, Michael, Bähr, Mathias, Lingor, Paul, Tönges, Lars·2017·Frontiers in Pharmacology
DOI 10.3389/fphar.2017.00017PMC PMC5281550
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Abstract

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.

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  • ROCK inhibition at a more advanced disease stage in SOD1G93A mice does not reduce microglial infiltration at the neuropathological level.

    “ROCK inhibition in a more advanced disease stage in SOD1G93A mice did not show increased motor neuron survival nor reduced microglial infiltration at the neuropathological level, although motor function was improved in male mice [213].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [213]

  • ROCK inhibition at a more advanced disease stage improves motor function in male SOD1G93A mice.

    “ROCK inhibition in a more advanced disease stage in SOD1G93A mice did not show increased motor neuron survival nor reduced microglial infiltration at the neuropathological level, although motor function was improved in male mice [213].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [213]

  • ROCK inhibition at a more advanced disease stage in SOD1G93A mice does not increase motor neuron survival.

    “ROCK inhibition in a more advanced disease stage in SOD1G93A mice did not show increased motor neuron survival nor reduced microglial infiltration at the neuropathological level, although motor function was improved in male mice [213].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [213]

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Authors
Günther, R., Balck, A., Koch, J. C., Nientiedt, T., Sereda, M., Bähr, M., Lingor, P., & Tönges, L.
Affiliations
  • Universitätsmedizin Göttingen (DE)
  • Max Planck Institute of Experimental Medicine (DE)
Corresponding author
Günther, René
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2017-01-31
Volume
8
Pages
17-17
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2017.00017
PMC
PMC5281550
OpenAlex
W2580016969
Cited by
47
References
2
Citations by year
2026: 4 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 1
FWCI
3.35
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • GRO (submittedVersion, cc-by)
Funders
  • Universitätsmedizin Göttingen
  • Deutsche Forschungsgemeinschaft
  • Else Kröner-Fresenius-Stiftung
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
amyotrophic lateral sclerosis, fasudil, Rho kinase inhibition, SOD1 G93A mice, symptomatic treatment, motor function, motor neurons, microglia, survival, disease-modifying therapy, riluzole

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