Systemic enzyme delivery by blood-brain barrier-penetrating SapC-DOPS nanovesicles for treatment of neuronopathic Gaucher disease.

ABSTRACT:

Background

Enzyme replacement therapy (ERT) can positively affect the visceral manifestations of lysosomal storage diseases (LSDs). However, the exclusion of the intravenous ERT agents from the central nervous system (CNS) prevents direct therapeutic effects.

Methods

Using a neuronopathic Gaucher disease (nGD) mouse model, CNS-ERT was created using a systemic, non-invasive, and CNS-selective delivery system based on nanovesicles of saposin C (SapC) and dioleoylphosphatidylserine (DOPS) to deliver to CNS cells and tissues the corrective, functional acid β-glucosidase (GCase).

Findings

Compared to free GCase, human GCase formulated with SapC-DOPS nanovesicles (SapC-DOPS-GCase) was more stable in serum, taken up into cells, mostly by a mannose receptor-independent pathwa

SUBMITTER: Sun Y 

PROVIDER: S-EPMC7251241 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature