Robust LC–MS/MS methods for analysis of heparan sulfate levels in CSF and brain for application in studies of MPS IIIA
| Autor: | Åsa Makower, Susanne Gustavsson, Agneta Tjernberg, Stefan Svensson Gelius, Tommy Andersson, Juliette Janson, Erik Arnelöf, Per-Olof Edlund |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Hydrolases
Mucopolysaccharidosis Clinical Biochemistry Clinical Chemistry Tests Analytical Chemistry Glycosaminoglycan Mice Mucopolysaccharidosis III 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cerebrospinal fluid Tandem Mass Spectrometry Lc ms ms medicine Animals General Pharmacology Toxicology and Pharmaceutics Mucopolysaccharidosis Type IIIA 030304 developmental biology 0303 health sciences Heparinase Brain General Medicine Heparan sulfate Enzyme replacement therapy medicine.disease Molecular biology Medical Laboratory Technology chemistry Heparitin Sulfate 030217 neurology & neurosurgery Chromatography Liquid |
| Zdroj: | Bioanalysis. 11:1389-1403 |
| ISSN: | 1757-6199 1757-6180 |
| DOI: | 10.4155/bio-2019-0095 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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