Systemic Delivery of a Glucosylceramide Synthase Inhibitor Reduces CNS Substrates and Increases Lifespan in a Mouse Model of Type 2 Gaucher Disease
Figure 2
Systemic administration of GZ 161 reduces GluCer and GluSph levels in the K14 mouse brain.
K14 and WT mice were treated daily (IP) beginning at P4 with vehicle or 5 mg/kg GZ 161, and brains analyzed for GluCer and GluSph at P10. GZ 161-treated animals were asymptomatic at this time. Treatment with GZ 161 reduced K14 (A) GluCer levels by ∼70% and (B) GluSph levels by ∼60%. Post-treatment levels of both glycosphingolipids remained significantly elevated compared to their WT littermates. and genotypes were confirmed by post-mortem DNA analysis. *p<0.05. N = 4/group.