Figure 4.

Therapeutic enzyme distribution in the CNS of post-symptomatic AAV-treated SD cats. Tissues from post-symptomatic AAV-treated SD cats were collected at humane endpoint. (a) Shown are injection sites (white circles) and 0.6 cm coronal blocks of the brain (A-H) and spinal cord (I-O) as depicted in a previous study²¹. Brain blocks were halved, and the right half was assayed for enzyme activity. Lysosomal Hex activity (red) was visualized throughout the brain (b) and spinal cord (c) of early post-symptomatic AAV-treated SD cat 11-831 (SD + AAV) at 18.9 months old. Similarly, Hex activity was visualized throughout the brain (d) and spinal cord (e) of late post-symptomatic AAV-treated SD cat 11-994 (SD + AAV) at 11.5 months old. Representative control sections are shown from untreated normal cats along with untreated SD cats, which express ≤0.02 fold normal HexA activity in the brain and spinal cord. Corresponding HexA activity against MUGS substrate is shown below each block as fold normal level (fold N). Each block from treated and untreated SD cats is normalized to the corresponding block from age-matched normal controls (the mean value from 5 normal cats). HexA specific activity in normal control cats ranged from 28.1 ± 7.5 to 57.4 ± 5.7 nmol 4MU/mg protein/hr in the brain and from 6.7 ± 0.8 to 17.5 ± 3.2 nmol 4MU/mg/hr in the spinal cord.