Figure 4. NMDI-1 co-administration with gentamicin, but not NB84, enhances PTC suppression in Idua ^W392X mice.

Homozygous WT and Idua ^W392X mice were administered readthrough (RT) drugs gentamicin (GENT) or NB84 for 14 days without (−) or with (+) NMDI-1 administration during the final 3 days of treatment. α-L-iduronidase (Idua) specific activity was determined in A) brain and D) spleen. The data are expressed as the specific activity in the mutant mouse tissues relative to WT controls × 100 (% WT Idua Activity). Data in A & D are the mean +/− sd of values obtained from 3–4 mice per group, performed using ≥8 replicates (n = 3 or 4). p values above the brackets compare mice treated with NMDI-1 to those without NMDI-1 treatment. B, C, E, F) Sulfated GAG levels were quantitated in brain and spleen from WT mice (white bars) and from untreated and treated Idua ^W392X mice (gray bars). GAG levels were quantitated as micrograms GAGs per mg protein in B) brain and E) spleen from the gentamicin treatment group, or in C) brain and F) spleen from the NB84 treatment group. The dashed line represents the WT GAG level as a reference. Data in B, C, E, F are expressed as mean +/− sd of 15–18 assays from 5–6 mice for each experimental group (n =  5 or 6). p values above the columns compare treated versus untreated W392X mice. p values above the brackets compare mice co-treated with both RT drug and NMDI-1 compared to mice treated with RT drug alone.