Dipyridamole Ameliorates Memory Impairment and Increases Hippocampal Calbindin Expression in Niemann Pick C1 Mice

Niemann Pick type C1 (NPC1) is a rare, fatal disorder characterized by endosomal lipid accumulation that leads to damage of both peripheral organs and central nervous system (cerebellum and hippocampus are especially affected). Currently, miglustat is the only approved drug for NPC1, thus the identification of new treatments is mandatory. We have previously demonstrated that the drug dipyridamole (DIP), an enhancer of adenosine signaling, can reduce the pathological phenotype in patient-derived fibroblasts. In this paper, we evaluated the in vivo effects of DIP in NPC1 mice. Male and female NPC1^nih mice were treated with DIP 30 mg/kg i.p. from 28 to 64 days of age. Motor function was assessed by Erasmus Ladder test, hippocampal cognitive decline by Novel Object Recognition test and brain pathology by immunofluorescence and biochemical assays. Peripheral pathology was evaluated by analyzing lipid accumulation in spleen and liver (HP-TLC). In NPC1, mice DIP rescued recognition memory and increased hippocampal expression of calbindin. On the contrary, the drug was unable to improve motor function, cerebellar pathology and lipid accumulation in spleen and liver. Our results demonstrated that DIP selectively ameliorates the cognitive impairment in NPC1 mice. This drug could thus represent a valuable therapeutic tool to be used in combination with other treatments in NPC1.