Figure 5. A limited therapeutic window in SMA model mice harboring the rescue allele.

SMN restoration at earlier time points generally correlated with (A) greater increases in body weight (n ≥ 4 for each genotype except P10 mice = 3; *P < 0.05, Student’s t test) and (B) enhanced motor performance assessed in righting ability tests (n ≥ 4 for each genotype, **P < 0.01; ***P < 0.001; 1-way ANOVA). (C) Equivalent increases in spinal cord SMN protein expression are observed in mutants bearing the rescue allele treated between P4 and P10. (D) Earlier restoration of SMN protein translates into greater phenotypic rescue in Kaplan-Meier survival curves. (E) Loss of spinal motor neurons and (F) gems is significantly mitigated following treatment only at the earliest (P4) time point (n = 3 for each cohort, ***P < 0.001; 1-way ANOVA). Data are represented as mean ± SEM.