Intravenous delivery of a chemically modified sulfamidase efficiently reduces heparan sulfate storage and brain pathology in mucopolysaccharidosis IIIA mice.

ABSTRACT: Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder (LSD) characterized by severe central nervous system (CNS) degeneration. The disease is caused by mutations in the SGSH gene coding for the lysosomal enzyme sulfamidase. Sulfamidase deficiency leads to accumulation of heparan sulfate (HS), which triggers aberrant cellular function, inflammation and eventually cell death. There is currently no available treatment against MPS IIIA. In the present study, a chemically modified recombinant human sulfamidase (CM-rhSulfamidase) with disrupted glycans showed reduced glycan receptor mediated endocytosis, indicating a non-receptor mediated uptake in MPS IIIA patient fibroblasts. Intracellular enzymatic activity and stability was not affected by chemical modification. A

SUBMITTER: Gustavsson S 

PROVIDER: S-EPMC6737345 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature