Aim: 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). Materials & methods: Two LC-MS/MS methods were adapted from literature methodology, one to measure HS metabolites (HSmet), the other to measure digests of HS after heparinase treatment (HSdig). Results: The HSmet and HSdig 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. Conclusion: The results of the two methods correlated and therefore the HSdig method can be used in clinical studies to determine HS levels in CSF from patients with MPS IIIA.
Aim: 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 IIIAmice after treatment with a chemically modified sulfamidase (CM-rhSulfamidase). Materials & methods: Two LC-MS/MS methods were adapted from literature methodology, one to measure HS metabolites (HSmet), the other to measure digests of HS after heparinase treatment (HSdig). Results: The HSmet and HSdig methods showed similar relative reduction of HS in brain after CM-rhSulfamidase administration to MPS IIIAmice and the reduction was reflected also in CSF. Conclusion: The results of the two methods correlated and therefore the HSdig method can be used in clinical studies to determine HS levels in CSF from patients with MPS IIIA.
Authors: Junhua Wang; Akhil Bhalla; Julie C Ullman; Meng Fang; Ritesh Ravi; Annie Arguello; Elliot Thomsen; Buyankhishig Tsogtbaatar; Jing L Guo; Lukas L Skuja; Jason C Dugas; Sonnet S Davis; Suresh B Poda; Kannan Gunasekaran; Simona Costanzo; Zachary K Sweeney; Anastasia G Henry; Jeffrey M Harris; Kirk R Henne; Giuseppe Astarita Journal: Int J Mol Sci Date: 2020-07-30 Impact factor: 5.923