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. Author manuscript; available in PMC: 2013 Jan 18.

Published in final edited form as: ACS Chem Neurosci. 2012 Jan 18;3(1):5–11. doi: 10.1021/cn200085z

The effect of BIP-135 on several phenotypes of SMA disease that are observed in transgenic mice. (A) Kaplan Meier survival curve of SMA KO mice treated once a day with BIP-135 at 75 mg/kg or vehicle (100% DMSO) from postnatal day 0 to 21. Post hoc Logrank and Wilcoxon tests showed significant differences between the two treatment groups (p = 0.0294 and 0.0266, respectively). The mean survival for KOs treated with BIP-135 was 14.7 + 0.4 days and 12.8 + 0.6 for vehicle treated control [F(1,45) = 5.314, p = 0.0258)]. (B) Effects of GSK-3 inhibitor BIP-135 at 75 mg/kg or its vehicle once a day on the SMA KO body weight. KO animals treated with BIP-135 showed an improvement in body weight in comparison to vehicle treated control (Figure 5B). ANOVA indicated a significant main effect for treatment [F(1,43) = 4.33, p = 0.0435)] and no significant treatment/age [F(15,540) = 1.43, p = 0.1289)] or treatment/gender/age interactions [F(30,540) = 1.12, p = 0.3016]. Improvement in body weight measures was observed after around P6. (C) Geotaxis test results for KO mice receiving BIP-135 at 75 mg/kg or its vehicle once a day. (a) Latency to complete the negative geotaxis test. There were no significant treatment effects [F(1,43) = 3.50, p = 0.0683] or treatment/age interaction [F(3,111) = 1.81, p = 0.1487] in the latency to re-orient upward in the geotaxis test between the two groups. (b) Percent of KO mice that completed the geotaxis test. Chi square test (4.625) indicated significant treatment effect at P12 (p = 0.0315), where more KO animals treated with BIP-135 completed the geotaxis test in comparison to the vehicle treated controls. (D) Tube test results for KO mice receiving BIP-135 at 75 mg/kg or its vehicle once a day. The tube test was performed at postnatal day 6, 8, 10 and 12. (a) Time spent hanging at the edge of the tube; (b) number of pulls; (c) hind-limb strength score; (d) tube test score. There was no significant treatment effect in the tube test parameters.

The effect of BIP-135 on several phenotypes of SMA disease that are observed in transgenic mice. (A) Kaplan Meier survival curve of SMA KO mice treated once a day with BIP-135 at 75 mg/kg or vehicle (100% DMSO) from postnatal day 0 to 21. Post hoc Logrank and Wilcoxon tests showed significant differences between the two treatment groups (p = 0.0294 and 0.0266, respectively). The mean survival for KOs treated with BIP-135 was 14.7 + 0.4 days and 12.8 + 0.6 for vehicle treated control [F(1,45) = 5.314, p = 0.0258)]. (B) Effects of GSK-3 inhibitor BIP-135 at 75 mg/kg or its vehicle once a day on the SMA KO body weight. KO animals treated with BIP-135 showed an improvement in body weight in comparison to vehicle treated control (Figure 5B). ANOVA indicated a significant main effect for treatment [F(1,43) = 4.33, p = 0.0435)] and no significant treatment/age [F(15,540) = 1.43, p = 0.1289)] or treatment/gender/age interactions [F(30,540) = 1.12, p = 0.3016]. Improvement in body weight measures was observed after around P6. (C) Geotaxis test results for KO mice receiving BIP-135 at 75 mg/kg or its vehicle once a day. (a) Latency to complete the negative geotaxis test. There were no significant treatment effects [F(1,43) = 3.50, p = 0.0683] or treatment/age interaction [F(3,111) = 1.81, p = 0.1487] in the latency to re-orient upward in the geotaxis test between the two groups. (b) Percent of KO mice that completed the geotaxis test. Chi square test (4.625) indicated significant treatment effect at P12 (p = 0.0315), where more KO animals treated with BIP-135 completed the geotaxis test in comparison to the vehicle treated controls. (D) Tube test results for KO mice receiving BIP-135 at 75 mg/kg or its vehicle once a day. The tube test was performed at postnatal day 6, 8, 10 and 12. (a) Time spent hanging at the edge of the tube; (b) number of pulls; (c) hind-limb strength score; (d) tube test score. There was no significant treatment effect in the tube test parameters.