(A) Distribution of ASOs in the Rhesus monkey brain visualized with immunostaining (anti-pan ASO) and counterstained for nuclei with hematoxylin following a 21 day intrathecal infusion of 4 mg/day ASO targeting monkey huntingtin (MkHuASO), including (A, bottom right) pyramidal neurons of the cortex and (A, bottom left) medium spiny neurons in the caudate.
(B) ASO distribution in the hippocampus and (B, bottom right) neurons in the dentate gyrus.
(C) ASO accumulation in a coronal section including the pons and cerebral aqueduct, CA; ASO is present in pontine cell bodies despite low levels of ASO accumulation in the surrounding tissue (lower panel).
(D) ASO accumulation in the cerebellum and surrounding brain regions.
(E) ASO accumulation in motor neurons in the spinal cord.
(F) mRNA levels of monkey huntingtin from various brain regions immediately following infusion, as determined by qPCR (n=3 per treatment, two-tailed unpaired t-tests).
(G) Monkey huntingtin mRNA levels in the anterior (frontal) cortex (red), posterior (occipital) cortex (orange), and cervical spinal cord (yellow), 0, 2, 4 and 8 weeks post-treatment termination (n=3 per treatment, two-way ANOVA, Bonferroni post hoc test). Data expressed as mean ± SEM, percent (%) of RNA relative to saline treated controls (blue). Asterisk (*p<0.5, **p<0.01, ***p<0.001) denotes statistically significant differences. See also Figure S7.