Dose Response of BMN 250 on Lysosomal Storage Pathology at 28 Days following 1, 3, 10, 40, or 100 μg ICV Doses Four Times over 2 Weeks
(A) NAGLU catalytic activity, steady-state total HS and disease-specific NRE biomarkers, and β-hexosaminidase enzyme activity measured in brain homogenate (mean ± SEM; VEH, vehicle-treated Naglu−/− mice; n = 11; 1 and 3 μg BMN 250, n = 6; 10 μg BMN 250, n = 10; 40 and 100 μg BMN 250, n = 4; VEH Naglu+/+, n = 2. Bottom: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 versus VEH Naglu−/−. Top: #p < 0.05, ##p < 0.01, ####p < 0.0001 versus VEH Naglu+/+. (B) Representative images of LAMP2 immunostain (white) from the cingulate cortex and entorhinal cortex, harvested from Naglu−/− mice treated with 10 μg doses of BMN 250 or vehicle (controls). (C) Representative high-resolution confocal images of immunostains for LAMP2 (green), NeuN (red), and DAPI (blue) in the entorhinal cortex of Naglu−/− mice treated with 10 μg doses of BMN 250 or vehicle (controls) for qualitative evaluation of neuronal LAMP2 signals.