Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease

A feline model of Niemann-Pick disease type C (NPC) was employed to evaluat e the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginn ing at 8 weeks of age; the cats remained on the diet for 150 and 270 days r espectively. The study goal was to lower the amount of low density lipoprot ein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological pro gression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-a ffected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-aff ected treated cats were similar to those seen in NPC-affected untreated cat s. Ganglioside concentrations in the NPC-affected treated cats and NPC-affe cted untreated cats were similar. Histological findings in liver sections f rom NPC-affected treated cats showed a diffuse uniform microvacuolar patter n within hepatocytes and Kupffer cells, in contrast to a heterogeneous macr o/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untr eated cats. Similar differences in vacuolar patterns were seen in splenic m acrophages. Although some hepatic parameters were modified, dietary cholest erol restriction did not appear to alter disease progression in NPC-affecte d kittens.