Makower Åsa, Arnelöf Erik, Andersson Tommy, Edlund Per-Olof, Gustavsson Susanne, Janson Juliette, Gelius Stefan Svensson, Tjernberg Agneta
Swedish Orphan Biovitrum, Tomtebodavägen 23A, 112 76 Stockholm, Sweden.
Bioanalysis. 2019 Aug;11(15):1389-1403. doi: 10.4155/bio-2019-0095.
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.
硫酸乙酰肝素（HS）的积累与神经退行性疾病III型黏多糖贮积症A（MPS IIIA）相关。在此，我们比较了用化学修饰的硫酸酯酶（CM-rhSulfamidase）治疗后的MPS IIIA小鼠脑和脑脊液（CSF）中的HS水平。两种液相色谱-串联质谱（LC-MS/MS）方法改编自文献方法，一种用于测量HS代谢产物（HS），另一种用于测量肝素酶处理后HS的消化产物（HS）。将CM-rhSulfamidase给予MPS IIIA小鼠后，HS和HS方法显示脑中HS的相对降低相似，并且CSF中也反映出这种降低。两种方法的结果相关，因此HS方法可用于临床研究，以确定MPS IIIA患者脑脊液中的HS水平。
