Synthetic high-density lipoprotein nanoparticles for the treatment of Niemann-Pick diseases.

ABSTRACT:

Background

Niemann-Pick disease type C is a fatal and progressive neurodegenerative disorder characterized by the accumulation of unesterified cholesterol in late endosomes and lysosomes. We sought to develop new therapeutics for this disorder by harnessing the body's endogenous cholesterol scavenging particle, high-density lipoprotein (HDL).

Methods

Here we design, optimize, and define the mechanism of action of synthetic HDL (sHDL) nanoparticles.

Results

We demonstrate a dose-dependent rescue of cholesterol storage that is sensitive to sHDL lipid and peptide composition, enabling the identification of compounds with a range of therapeutic potency. Peripheral administration of sHDL to Npc1 I1061T homozygous mice mobilizes cholesterol, reduces serum bilirubin, reduces

SUBMITTER: Schultz ML 

PROVIDER: S-EPMC6849328 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature