Cyclodextrins as Modifiers of Intracellular Cholesterol Trafficking in Niemann-Pick Disease Type C

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2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is an attractive drug candidate against Niemann-Pick disease Type C (NPC). However, the efficacy and safety of HPBCD treatment for NPC patients remain to be elucidated. This study was conducted to obtain the essential information on efficacy and safety of HPBCD treatment for NPC patients. 1) Weekly subcutaneous administrations of HPBCD at a dose of 1000-4000 mg/kg to Npc1-deficient mice ameliorated hepatomegaly and survival rates in the mice. 2) Compared with wild type mice, Npc1-deficient mice were substantially resistant to the lethality and the organ injury induced by HPBCD at higher doses. This study provides information on optimization of HPBCD treatment for NPC patients and also suggests Npc1 genotype should be considered in the safety evaluation of HPBCD using animals and cells.