In Niemann-Pick type C (NPC) disease, loss of function mutations in either NPC1 or NPC2 result in progressive accumulation of unesterified cholesterol (UC) and glycosphingolipids in all organs leading to neurodegeneration, pulmonary dysfunction and sometimes liver failure.....The key question now is whether delaying the start of 2HPβCD treatment until early adulthood when the amount of entrapped UC throughout the body is markedly elevated has any of the benefits found when treatment begins at 7 days of age. Npc1-/- and Npc1+/+ mice were given saline or 2HPβCD subcutaneously at 49, 56, 63, and 70 days of age, and used for tissue cholesterol and other measurements at 77 days. In the Npc1-/- mice, treatment with 2HPβCD from 49 days reduced whole-liver cholesterol content at 77 days from 33.0±1.0 to 9.1±0.05 mg/organ. Comparable improvements were seen in other organs such as spleen, and in the animal as a whole. There was a transient increase in biliary cholesterol concentration in the Npc1-/- mice after 2HPβCD. Plasma ALT and AST activities in the 77 day-old 2HPβCD-treated Npc1-/- mice were reduced. The lifespan of Npc1-/- mice given 2HPβCD marginally exceeded that of their saline-only controls (99±1.1 vs 94±1.4 days, P<0.05). Thus 2HPβCD is effective in mobilizing entrapped cholesterol in late-stage NPC disease leading to improved liver function.