ArticleBMC medicine2012
Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy.
Article in BMC medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges.Genes · 2024Review
- L-F001, a multifunctional fasudil-lipoic acid dimer, antagonizes hypoxic-ischemic brain damage by inhibiting the TLR4/MyD88 signaling pathway.Brain and behavior · 2023Article
- MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice.Molecular therapy. Nucleic acids · 2023Article
- Spinal astrocyte dysfunction drives motor neuron loss in late-onset spinal muscular atrophy.Acta neuropathologica · 2023Article
- Autophagy in spinal muscular atrophy: from pathogenic mechanisms to therapeutic approaches.Frontiers in cellular neuroscience · 2023Review
- Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice.Skeletal muscle · 2022Article
- Multitarget Hybrid Fasudil Derivatives as a New Approach to the Potential Treatment of Amyotrophic Lateral Sclerosis.Journal of medicinal chemistry · 2022Article
- Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review.International journal of molecular sciences · 2021Review
- Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading.Communications biology · 2021Article
- Survival motor neuron deficiency slows myoblast fusion through reduced myomaker and myomixer expression.Journal of cachexia, sarcopenia and muscle · 2021Article
- Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell reports. Medicine · 2021Review
- Profilin2 regulates actin rod assembly in neuronal cells.Scientific reports · 2021Article
- AAV9-DOK7 gene therapy reduces disease severity in SmnBiochemical and biophysical research communications · 2020Article
- Drug Screening and Drug Repositioning as Promising Therapeutic Approaches for Spinal Muscular Atrophy Treatment.Frontiers in pharmacology · 2020Review
- Effect of Fasudil on remyelination following cuprizone-induced demyelination.CNS neuroscience & therapeutics · 2020Article
- The Need for SMN-Independent Treatments of Spinal Muscular Atrophy (SMA) to Complement SMN-Enhancing Drugs.Frontiers in neurology · 2020Review
- Elevated BMP and Mechanical Signaling Through YAP1/RhoA Poises FOP Mesenchymal Progenitors for Osteogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- AAV9-mediated delivery of miR-23a reduces disease severity in Smn2B/-SMA model mice.Human molecular genetics · 2019Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSpinal muscular atrophy (SMA) is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (SMN1) gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (ROCK) pathway is misregulated in cellular and animal SMA models, and that inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan of a mouse model of SMA. In the present study, we evaluated the therapeutic potential of the clinically approved ROCK inhibitor fasudil.
methodsFasudil was administered by oral gavage from post-natal day 3 to 21 at a concentration of 30 mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For the Kaplan-Meier survival analysis, the log-rank test was used and survival curves were considered significantly different at P < 0.05. For the remaining analyses, the Student's two-tail t test for paired variables and one-way analysis of variance (ANOVA) were used to test for differences between samples and data were considered significantly different at P < 0.05.
resultsFasudil significantly improves survival of SMA mice. This dramatic phenotypic improvement is not mediated by an up-regulation of Smn protein or via preservation of motor neurons. However, fasudil administration results in a significant increase in muscle fiber and postsynaptic endplate size, and restores normal expression of markers of skeletal muscle development, suggesting that the beneficial effects of fasudil could be muscle-specific.
conclusionsOur work underscores the importance of muscle as a therapeutic target in SMA and highlights the beneficial potential of ROCK inhibitors as a therapeutic strategy for SMA and for other degenerative diseases characterized by muscular atrophy and postsynaptic immaturity.
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Registered trials
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