In vivo Efficacy and Safety Evaluation of Lactosyl-β-cyclodextrin as a Therapeutic Agent for Hepatomegaly in Niemann-Pick Type C Disease.

ABSTRACT: Niemann-Pick type C disease (NPC) is a fatal, autosomal recessive disorder, which causes excessive accumulation of free cholesterol in endolysosomes, resulting in progressive hepatomegaly and neurodegeneration. Currently, 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) is used at a high dose for the treatment of NPC, risking lung toxicity and hearing loss during treatment. One method to reduce the required dose of HP-β-CyD for the treatment of hepatomegaly is to actively deliver β-cyclodextrin (β-CyD) to hepatocytes. Previously, we synthesized lactosyl-β-CyD (Lac-β-CyD) and demonstrated that it lowers cholesterol in NPC model liver cells. In the present study, we studied the efficacy and safety of Lac-β-CyD treatment of hepatomegaly in Npc1-/- mice. After subcutaneous administration, Lac-β-CyD a

SUBMITTER: Maeda Y 

PROVIDER: S-EPMC6566927 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature