Extended Data Fig. 10: Effects of low-titer AAV-Isl1+AAV-Lhx3 treatment in SOD1G93A mice.
a, The probability of remaining asymptomatic as a measure of tremor onset in AAV-mCherry vs AAV-Isl1+AAV-Lhx3-treated SOD1G93A mice was compared by Log-rank (Mantel-Cox) tests (n = 10–13 animals per treatment per sex). Separate analyses were performed for male vs. female animals. For females, AAV-Isl1+AAV-Lhx3 treatment delayed tremor onset by 15 days (p = 0.0036). For males, tremor onset was delayed by 5 days but was not significant (p = 0.1138). b, The probability of survival in the same animals as (a) compared by Log-rank (Mantel-Cox) test. Mean survival was as follows: AAV-mCherry males = 161 days; AAV-Isl1+AAV-Lhx3 males = 160.5 days; AAV-mCherry females = 166 days; AAV-Isl1+AAV-Lhx3 females = 169 days. No significant effects of treatment on survival were observed for females (p = 0.8807) or males (p = 0.2687). c, Representative immunostaining for CHAT+ motor neuron survival and transgene expression in a subset of animals from a,b collected at endstage (n = 6 mice). mCherry expression generally remains strong, while ISL1 and LHX3 expression are sparse or absent. d, In the subset of AAV-Isl1+AAV-Lhx3-treated animals analyzed at endstage there was a trend toward a significant correlation between the percentage of CHAT+ motor neurons per hemisection expressing ISL1 or LHX3 and the number of surviving motor neurons per hemisection in the L4-L5 region of the spinal cord (n = 6 mice; R2 = 0.6200, p = 0.0630). 6 70 µm hemisections were quantified per animal. Circles represent females; triangles represent males.
