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It is caused by mutations\/deletions of the survival motor neuron 1 (<jats:italic>SMN1<\/jats:italic>) 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Fasudil 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 <jats:italic>P<\/jats:italic> &lt; 0.05. For the remaining analyses, the Student's two-tail <jats:italic>t<\/jats:italic> 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 <jats:italic>P<\/jats:italic> &lt; 0.05.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Fasudil 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1741-7015-10-24","type":"journal-article","created":{"date-parts":[[2012,3,7]],"date-time":"2012-03-07T11:14:15Z","timestamp":1331118855000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy"],"prefix":"10.1186","volume":"10","author":[{"given":"Melissa","family":"Bowerman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsay M","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin G","family":"Boyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie L","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Kothary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,3,7]]},"reference":[{"key":"507_CR1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1006\/nbdi.1996.0010","volume":"3","author":"TO Crawford","year":"1996","unstructured":"Crawford TO, Pardo CA: The neurobiology of childhood spinal muscular atrophy. 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