Figure 4.

Therapeutic benefit in Sandhoff disease (SD) cats after intrathalamic injection of AAVrh8 vectors expressing feline Hex. SD cats (n = 3) were followed to the humane endpoint after bilateral thalamic injection of AAVrh8-fHEX vectors (1:1 ratio of α:β total dose = 3.2 × 10¹² g.e.). (a) Mean survival of treated SD cats (SD + AAV) was 10.4 months, a statistically significant increase compared with nine untreated cats (SD; P = 0.0064, log-rank test). (b) Injection sites (white circles) and 0.6 cm coronal brain blocks (A–H) are shown. (c) Naphthol staining for Hex activity (red) is shown for untreated normal and SD cat brains. The fold normal Hex activity (measured by MUGS substrate) is listed below each brain block. (d) Naphthol staining for one representative AAV-treated SD cat (SD + AAV, 7-856) demonstrates Hex activity throughout the cerebrum (A–E) with minor activity in brainstem and cerebellum (F–H). MUGS activity ranged from 0.18- to 8.1-fold normal. Letter designations correspond to b. AAV, adeno-associated virus; g.e., genome equivalents; MUGS, 4-methylumbelliferyl 6-sulfo-2-acetamido-2-deoxy-β-D-glucopyranoside.