Fig. 5.

ASO-10-27 treatment improves function and survival of SMA mice. (A to F) Results of the body weight (A and B), righting reflex(C and D), gripstrength (E), and hindlimb splay (F) at 8 days (A and C) and 16 days (B, D, E, and F). (G) A single administration of different doses (0.5 to 8 μg) of ASO-10-27 was injected into P0 mice with severe SMA, and their survival was plotted on a Kaplan-Meier curve. The median survival was 18 to 26 days, which was a significant improvement compared to untreated SMA mice (0.5 μg, P = 0.0237; 1 μg, P = 0.0007; 2 μg, P = 0.0001; 4 μg, P < 0.0001; 8.0 μg, P = 0.0004). In contrast, SMA mice treated with ASO-mismatched oligonucleotides did not show an increase in survival (4 μg, P = 0.5081). (H) Percent weight gains between P14 and P7 with the different doses of ASO-10-27 in SMA mice. SMN, untreated SMA mice (n = 18); MM, SMA mice treated with 4 μg of ASO-mismatched oligonucleotide (n = 14); SMA mice treated with 0.5 μg (n = 10), 1 μg (n = 9), 2 μg (n = 10), 4 μg (n = 20), or 8 μg (n = 13) of ASO-10-27. The P values between the different treatment groups in (A) to (F) were determined by one-way ANOVA and Bonferroni multiple post hoc comparisons (P < 0.05; P < 0.01; P < 0.001). The P values in the survival curve were analyzed with the Mantel-Haenszel test by comparing each treatment group to the untreated SMA group. Data are means ± SEM.