Distribution of heparan sulfate and dermatan sulfate in mucopolysaccharidosis type II mouse tissues pre- and post-enzyme-replacement therapy determined by UPLC-MS/MS

Aim: Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by a deficiency of the iduronate-2-sulfatase enzyme leading to the accumulation of heparan sulfate (HS) and dermatan sulfate (DS) in organs and biological fluids. Enzyme-replacement therapy is available for affected patients. Results/methodology: A 6-min UPLC-MS/MS method was developed/validated for HS and DS quantification in mouse tissues and biological fluids with high accuracy and precision. In MPS II mice, HS was more abundant than DS. 8-week enzyme-replacement therapy significantly reduced HS and DS levels in all matrices, except the brain. These reduced levels were maintained over a 16-week extended treatment period. Conclusion: The devised method is sensitive, robust and useful for the evaluation of biomarker distribution in MPS II mice.