Effect of long-term oral BPN-14136 administration in Abca4−/− mice.
A, serum RBP4 levels were measured in vehicle-treated Abca4−/− mice (black circles; n = 7) and BPN-14136–treated Abca4−/− mice (blue squares, n = 8) at the indicated time points. BPN-14136 formulated in a chow was dosed at 20 mg/kg. Compared with day 0, statistically significant 90% RBP4 reduction at weeks 2, 6, and 12 was seen in the BPN-14136 treatment group (two-way ANOVA with Sidak post hoc test, p < 0.0001). Error bars show S.D. Each data point on the graph represents a serum RBP4 concentration from an individual animal. B, effects of BPN-14136 treatment on the level of the lipofuscin fluorophore A2E in eyes of the Abca4−/− mice. Bisretinoids were extracted from the eyecups of vehicle-treated Abca4+/+ WT mice (black circles, 8 eyes), vehicle-treated Abca4−/− knockout mice (red squares, 14 eyes), and BPN-14136–treated Abca4−/− mice (blue triangles, 16 eyes) after 12 weeks of dosing and analyzed by HPLC. A significant 50% reduction in A2E concentration was detected in BPN-14136–treated Abca4−/− mice compared with vehicle-treated knockout controls (one-way ANOVA with Holm-Sidak post hoc test, p < 0.0001 (****)).