Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy
1 Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6
2 Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5
3 Department of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5
BMC Medicine 2012, 10:24 doi:10.1186/1741-7015-10-24Published: 7 March 2012
Additional file 1:
Effect of low and high doses of fasudil. A low dose of fasudil (30 mg/kg once daily), a high dose of fasudil (30 mg/kg twice daily from P3-P6; 50 mg/kg twice daily from P7-P13; 75 mg/kg twice daily from P14-P21), or vehicle (water) was administered by gavage. The different groups analyzed were: untreated wild type (WT) (n = 10), fasudil (high dose)-treated Smn2B/+ (n = 16), vehicle-treated Smn2B/- (n = 16), fasudil (low dose)-treated Smn2B/- (n = 6) and fasudil (high dose)-treated Smn2B/- (n = 10) mice. A) Survival curves show that the low fasudil dosage regimen had no effect while the high fasudil dosage regimen significantly increases the lifespan of Smn2B/- mice when compared to vehicle-treated Smn2B/- mice (*P = 0.03; # indicates death due to malocclusion of the teeth). B) Survival curve shows that the high fasudil dosage regimen has non-negligible toxic effects on both Smn2B/- mice and the normal Smn2B/+ littermates.
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Additional file 2:
Smn2B/- mice treated with fasudil show improved gait and movement. A movie of aging fasudil- (left mouse) and vehicle-treated (right mouse) Smn2B/- mice (two months of age). The fasudil-treated mouse displays the agility and ability to freely walk and move around the cage while still displaying a minor neurological phenotype. The vehicle-treated Smn2B/- mouse displays a severe neurological phenotype and reduced motor functions.
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