(A, C, E, and E′) An
increase in TPP1 in CSF was measured with an enzyme activity assay (see also
table S2).
(B, D, F, and
F′) NAbs in CSF were determined by a neutralization assay:
TPP1-deficient mouse embryonic fibroblasts were exposed to a mixture of canine
TPP1 plus dog CSF collected before and after treatment. Data were normalized to
baseline (pretreatment) values. (A and B) TPP1 activity and NAbs in two dogs
(DC013 and DC014) given mycophenolate mofetil treatment starting at day 44
relative to vector infusion (see table S1 for information on vector dose and drug treatment
for each dog). (C and D) TPP1 activity and NAbs in two dogs (DC015 and DC016)
given mycophenolate mofetil starting at day 33 relative to vector infusion. (E,
E′, F, and F′) TPP1 activity and NAbs in three dogs (DC018,
DC019, and DC020) given mycophenolate mofetil starting at day −5
relative to vector infusion. Vector infusions were at about 90 days of age in
all cases. *TPP1 in CSF from DC019 was 0.3 pmol/mg protein or
100% of normal. **CSF from DC020 showed no detectable
TPP1 uptake at this time point, indicating high levels of NAbs.