A water-soluble β-cyclodextrin polymer reduces cholesterol accumulation and autophagy dysfunction in vitro and in Niemann-Pick type C disease model mice.

Niemann-Pick disease type C (NPC) and Alzheimer's disease (AD) are characterised by cognitive dysfunction and neurological impairment. In both diseases, the abnormal accumulation and disruption of cholesterol homeostasis in the brain may contribute to the pathogenesis and exacerbation of symptoms. Cyclodextrins (CDs) are attracting attention as therapeutic agents that can reduce free cholesterol in the brain. A water-soluble β-CD polymer (β-CDP) consisting of multiple β-CDs cross-linked by epichlorohydrin was recently developed and reportedly has improved safety and higher circulation time in the bloodstream. In this study, we evaluated the potential of β-CDP as a promising therapeutic agent for NPC and AD. β-CDP lowered free cholesterol levels and reversed autophagy dysfunction in cholesterol-accumulated human neuroblastoma cells. Longer circulation time in the bloodstream and reduced cholesterol accumulation in NPC mice were also observed after its subcutaneous administration. These results suggest that β-CDP may be a safe therapeutic agent in the treatment of NPC and AD.