Niemann Pick disease (NPD) or acid sphingomyelinase deficiency (ASMD) is a rare lipid storage disorder caused by a mutation in the SPMD1 gene, coding for the enzyme acid sphingomyelinase (ASM).
Background
ASM catalyzes hydrolysis of sphingomyelin, a major lipid component of cell membranes and the myelin sheath, to ceramide and phosphocholine. Due to decreased or absent activity of ASM, sphingomyelin accumulates. Research shows that excess lipid in cells, like the sphingolipid accumulation in ASMD, traps cholesterol and impedes efflux facilitated by apolipoprotein-A1 and HDL. Lipid profiles are often disrupted with high total cholesterol, low HDL and high LDL leading to increased risk of atherosclerosis. We will investigate of this process can be influenced in vitro by incubation of fibroblasts with recombinant HDL.
Methods
We will collect fasting plasma samples and fibroblasts derived from skin biopsies of Fabry patients, ASMD patients, Niemann-Pick type C patients, Gaucher patients and healthy subjects. We will determine plasma LCAT activity and HDL composition; SREBP-signaling and LDL-receptor abundance and activity; assess lipid content in fibroblasts and determine whether this is influenced by treatment with recombinant HDL.
Start date
09-2018
Contact
E.C.B. Eskes, PhD Candidate
Dept of Internal Medicine, div of Endocrinology and Metabolism, F5-175
Academic Medical Center
Meibergdreef 9
1105 AZ Amsterdam
T 0031-20-56666791 E e.c.eskes@amc.uva.nl