Pentosan Polysulfate Treatment of Mucopolysaccharidosis Type IIIA Mice

  • Ningning Guo
  • Victor DeAngelis
  • Changzhi Zhu
  • Edward H. Schuchman
  • Calogera M. SimonaroEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 43)


Overall Goal: This study was designed to evaluate the impact of pentosan polysulfate (PPS) treatment on mice with mucopolysaccharidosis (MPS) type IIIA (Sanfilippo A syndrome; OMIM 252900).

Protocol: Three groups of MPS IIIA mice were evaluated: 1-week-old mice treated with subcutaneous (subQ) PPS at 25 mg/kg once weekly for 31 weeks (group 1); 5-month-old mice treated with subQ PPS once weekly at 50 mg/kg for 12 weeks (group 2); and 5-week-old mice treated by continual intracerebroventricular (ICV) PPS infusion for 11 weeks (60 μg/kg/day). Treated MPS IIIA mice and controls were assessed by measuring plasma cytokine levels, histologic analyses of systemic organs, and analyses of various neuroinflammatory, neurodegenerative, and lysosomal disease markers in their brains. Neurobehavioral testing also was carried out.

Results: As seen in other MPS animal models, subQ PPS treatment reduced plasma cytokine levels and macrophage infiltration in systemic tissues. ICV administration did not elicit these systemic effects. SubQ PPS administration also significantly impacted brain neuropathology, inflammation, and behavior. The effect of early subQ treatment was more significant than dose. Surprisingly, ICV PPS treatment had intermediate effects on most of these brain markers, perhaps due to the limited dose and/or duration of treatment. Consistent with these neuropathological findings, we also observed significant improvements in the hyperactivity/anxiety and learning behaviors of the MPS IIIA mice treated with early subQ PPS.


Central nervous system Mucopolysaccharidosis type IIIA Neuroinflammation Pentosan polysulfate 



Blood brain barrier


Bovine serum albumin


Central nervous system


Cerebral spinal fluid




Enzyme-linked immunosorbent assays




Granulocyte colony stimulating factor


Glial fibrillary acidic protein




Heparan sulfate


Hematopoietic stem cell transplantation




Interleukin-1 alpha


Isolectin B4




Lysosomal integral membrane protein-2


Lysosomal storage disorder


Monocyte chemoattractant protein-1




Macrophage inflammatory protein-1 alpha




Phosphate buffered saline


Pentosan polysulfate





The research was funded by the Stop Sanfilippo Foundation.

Supplementary material

477606_1_En_96_MOESM1_ESM.pptx (56.5 mb)
Supplementary Fig. 1 Semi-quantitative assessment of storage vacuoles in the livers, spleens, and kidneys of MPS IIIA mice treated by subQ PPS. Scoring was performed by three independent laboratory technicians who were blinded to the treatment groups. The scoring system is described in the Materials and Methods. At least three slides were scored per tissue per mouse. *p = <0.001 compared treated to age-matched untreated mice (PPTX 34 kb)
477606_1_En_96_MOESM2_ESM.pptx (56.5 mb)
Supplementary Fig. 2 Total GAG analysis of liver, spleen, and kidney extracts of MPS IIIA mice treated by subQ PPS. Total GAGs were determined by the Blyscan method using tissue extracts prepared from each mouse. n = 10 per group (PPTX 36 kb)


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Ningning Guo
    • 1
  • Victor DeAngelis
    • 1
  • Changzhi Zhu
    • 1
  • Edward H. Schuchman
    • 1
  • Calogera M. Simonaro
    • 1
    Email author
  1. 1.Department of Genetics and Genomic SciencesIcahn School of Medicine at Mount SinaiNew YorkUSA

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