(A) NAGLU enzymatic activity in 8-week-old Naglu^–/– mice (n = 12; 8 females, 4 males) treated at 4 weeks with AAV7-NAGLU-LAMP1 (AAV7) intravenously, compared with untreated Naglu^–/– mice (n = 10: 5 females, 5 males) and Naglu^+/– mice (n = 10; 5 females, 5 males). Horizontal lines represent means. Naglu^–/– mice have undetectable NAGLU activity (data not shown). (B–D) Total HS in serum, brains, and CSF of mice treated with AAV7-NAGLU-LAMP1 and controls. Box plots depict median (line), upper and lower quartiles (box bounds), and 10th and 90th centiles (whiskers). (E) NAGLU enzymatic activity in 4-week-old Naglu^–/– mice treated intracerebroventricularly at P1 or P2 with 6.5 × 10¹⁰ vector genomes (AAV9-High; n = 13; 3 females, 10 males) or 6.5 × 10⁹ vector genomes (AAV9-Low; n = 8: 4 females, 4 males) per mouse of AAV9-Syn1-NAGLU-LAMP1, compared with untreated Naglu^–/– mice (n = 8; 2 females, 6 males) and Naglu^+/– controls (n = 7; 3 females, 4 males). Horizontal lines represent means. Naglu^–/– mice have undetectable NAGLU activity (data not shown). (F–H) Total HS in serum, brains, and CSF of the mice treated with AAV9-Syn1-NAGLU-LAMP1 and controls. Box plots depict median (line), upper and lower quartiles (box bounds), and 10th and 90th centiles (whiskers). *P < 0.05, ***P < 0.001, vs. ^–/–. (I) Summary of experimental results. Tx, treatment. P values reflect pairwise comparisons of means. Values for all data points in graphs are reported in the Supporting Data Values file.