Targeted gene therapy reduces storage material accumulation in Ppt1−/− mice. (A) Representative confocal microscopy images of treated animals and controls at 7 mo showing the primary motor cortex, VPM/VPL of the thalamus, and ventral horn of the lumbar spinal cord with differential patterns of reduction of autofluorescent storage material accumulation in intracranially (IC-AAV2/9), intrathecally (IT-AAV2/9), and combination intracranially and intrathecally (IC/IT-AAV2/9) treated mice, compared with untreated Ppt1−/− and wild-type control mice. IC/IT-AAV2/9 mice show an overall greater reduction in AFSM than either IC-AAV2/9 or IT-AAV2/9 therapy alone. The dotted lines demarcate the boundary between the gray and white matter in spinal cord sections. [Scale bars, 100 μm and 25 μm (Insets).] (Insets) Selected from corresponding lower-power views. (B) Thresholding image analysis at 3-, 5-, and 7-mo time points showing a significant but differential pattern of the reduction of AFSM accumulation based on the site of vector administration, with IC/IT-treated mice showing the greatest overall reduction of AFSM. Significance is compared with untreated Ppt1−/− mice. Dots represent scatterplots of individual animals. *P < 0.05, **P < 0.01, ***P < 0.001, one-way ANOVA with post hoc Bonferroni correction. Values shown are mean ± SEM (n = 3 mice per group).