Weekly cyclodextrin administration normalizes cholesterol metabolism in nearly every organ of the Niemann-Pick type C1 mouse and markedly prolongs life

Pediatr Res. 2010 Oct;68(4):309-15. doi: 10.1203/PDR.0b013e3181ee4dd2.


Niemann-Pick type C1 (NPC1) disease arises from a mutation inactivating NPC1 protein that normally moves unesterified cholesterol from the late endosomal/lysosomal complex of cells to the cytosolic compartment for processing. As a result, cholesterol accumulates in every tissue of the body causing liver, lung, and CNS disease. Treatment of the murine model of this disease, the npc1 mouse, s.c. with β-cyclodextrin (4000 mg/kg) one time each week normalized cellular cholesterol metabolism in the liver and most other organs. At the same time, the hepatic dysfunction seen in the untreated npc1 mouse was prevented. The severity of cerebellar neurodegeneration also was ameliorated, although not entirely prevented, and the median lifespan of the animals was doubled. However, in contrast to these other organs, lung showed progressive macrophage infiltration with development of lipoid pneumonitis. These studies demonstrated that weekly cyclodextrin administration overcomes the lysosomal transport defect associated with the NPC1 mutation, nearly normalizes hepatic and whole animal cholesterol pools, and prevents the development of liver disease. Furthermore, this treatment slows cerebellar neurodegeneration but has little or no effect on the development of progressive pulmonary disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Animals
  • Anticholesteremic Agents / administration & dosage*
  • Biological Transport
  • Brain / drug effects
  • Brain / metabolism
  • Cholesterol / metabolism*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Injections, Subcutaneous
  • Intracellular Signaling Peptides and Proteins
  • Liver / drug effects
  • Liver / metabolism
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control
  • Lung / drug effects
  • Lung / metabolism
  • Lung Diseases / metabolism
  • Lung Diseases / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Mutation
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Nerve Degeneration / prevention & control
  • Niemann-Pick Disease, Type C / drug therapy*
  • Niemann-Pick Disease, Type C / genetics
  • Niemann-Pick Disease, Type C / metabolism
  • Niemann-Pick Disease, Type C / pathology
  • Proteins / genetics*
  • Time Factors
  • beta-Cyclodextrins / administration & dosage*


  • Anticholesteremic Agents
  • Intracellular Signaling Peptides and Proteins
  • Npc1 protein, mouse
  • Proteins
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Cholesterol