Figure 7. Survival and mRNA levels in severe SMA pups treated with antibody-PMOs.

(A) Survival following single subcutaneous administration of 20 mg/kg 8D3₁₃₀-PMO (n = 7), NIP228-PMO (n = 15), or 8D3₁₃₀-scrambled PMO (n = 11) or 0.9% saline (n = 17). Median survival was 24, 12, 11, and 7 days, respectively. Mean survival after treatment with 8D3₁₃₀-PMO was significantly greater than NIP228-PMO, P < 0.0001 (log-rank [Mantel-Cox] test). (B) Survival following single subcutaneous administration of 50 mg/kg 8D3₁₃₀-PMO (n = 12), NIP228-PMO (n = 11), or 8D3₁₃₀-scrambled PMO (n = 11) or 0.9% saline (n = 17). Median survival was 22, 21, 8, and 7 days, respectively. Both 8D3₁₃₀-PMO and NIP228-PMO was statistically significant from 0.9% saline–treated group, P < 0.0001 (log-rank [Mantel-Cox] test). However, there was no statistical difference between 8D3₁₃₀-PMO and NIP228-PMO. (C–H) qRT-PCR measure of mRNA from tissues treated with 50 mg/kg antibody-PMO and collected 7 days postadministration. Results were normalized to saline treatment controls. FLSMN2 mRNA represented as ratio to total SMN2 transcripts. One-way ANOVA with Tukey’s multiple-comparison test. All data represent mean values ± SD of 2 replicates. P value representations: ****P < 0.001, *P < 0.05.