Therapeutic potential of cyclodextrins in the treatment of Niemann-Pick type C disease.

Niemann-Pick type C (NPC) disease is an autosomal recessive neurovisceral lipid and storage disorder characterized by abnormal sequestration of unesterified cholesterol within the late endosomal/lysosomal compartment of all cells in the body. This disease primarily affects children and is characterized by hepatic and pulmonary dysfunction, neurodegeneration and death at an early age. Currently, there is no effective treatment for NPC disease. It was recently discovered that 2-hydroxypropyl-β-cyclodextrin (2HPBCD), when administered systemically to a murine model of either NPC1 or NPC2 disease, significantly reduced lysosomal cholesterol accumulation in almost every organ, delayed the progression of neurodegeneration and significantly prolonged lifespan by allowing trapped cholesterol within the late endosome/lysosome to be released. When 2HPBCD was administered directly into the CNS of Npc1-/- mice, neurodegeneration was completely prevented. This review will explore the pathophysiology of NPC disease and the use of 2HPBCD as a possible therapeutic modality.