Fig. 6. Evaluation of MPS I dog aortas.

Some MPS I dogs received neonatal IV injection of 1×10¹⁰ TU/kg of the RV hAAT-cIDUA-WPRE (RV-treated) as previously described [14], while other MPS I and normal dogs were untreated. Aortas were evaluated at 1 to 1.8 years of age. A. Elastin fragmentation. Elastin fragmentation was quantified in the inner region of the aorta (see Region 1 in Fig. 2) for the indicated number (N) of animals, as described in Fig. 3, and the average +/− SEM is shown. RV-treated MPS I dogs that were evaluated included two dogs with relatively low serum IDUA activity [I-99 with 23 U/ml (2-fold normal) serum IDUA activity and I-101 with 27 U/ml (2-fold normal)], and two dogs with relatively high serum IDUA activity [I-107 with 553 U/ml (43-fold normal), and I-140 with 888 U/ml (68-fold normal)]. The p value determined using ANOVA with Tukey post-hoc analysis for comparison of the groups joined with a bracket are shown. B. mRNA levels. mRNA levels for the indicated genes in aortas of 8 normal, 3 untreated MPS I, and 3 RV-treated MPS I dogs are shown as a ratio to the values found in normal dogs. The RV-treated dogs that were analyzed included two dogs with relatively low expression (I-99 and I-101) and one dog with relatively high expression (I-107). C and D. Cathepsin and MMP-12 enzyme activity. Cathepsin and MMP-12 assays were performed as described in Fig. 5A and 5C for the number of animals described in panel A.