Robust LC-MS/MS methods for analysis of heparan sulfate levels in CSF and brain for application in studies of MPS IIIA.

Accumulation of heparan sulfate (HS) is associated with the neurodegenerative disorder Mucopolysaccharidosis type IIIA (MPS IIIA). Here, we compare HS levels in brain and cerebrospinal fluid (CSF) of MPS IIIA mice after treatment with a chemically modified sulfamidase (CM-rhSulfamidase). Two LC-MS/MS methods were adapted from literature methodology, one to measure HS metabolites (HS), the other to measure digests of HS after heparinase treatment (HS). The HS and HS methods showed similar relative reduction of HS in brain after CM-rhSulfamidase administration to MPS IIIA mice and the reduction was reflected also in CSF. The results of the two methods correlated and therefore the HS method can be used in clinical studies to determine HS levels in CSF from patients with MPS IIIA.