Long circulating enzyme replacement therapy rescues bone pathology in mucopolysaccharidosis VII murine model

Mol Genet Metab. 2012 Sep;107(1-2):161-72. doi: 10.1016/j.ymgme.2012.07.002. Epub 2012 Jul 14.


Mucopolysaccharidosis (MPS) type VII is a lysosomal storage disease caused by deficiency of the lysosomal enzyme β-glucuronidase (GUS), leading to accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) effectively clears GAG storage in the viscera. Recent studies showed that a chemically modified form of GUS (PerT-GUS), which escaped clearance by mannose 6-phosphate and mannose receptors and showed prolonged circulation, reduced CNS storage more effectively than native GUS. Clearance of storage in bone has been limited due to the avascularity of the growth plate. To evaluate the effectiveness of long-circulating PerT-GUS in reducing the skeletal pathology, we treated MPS VII mice for 12 weeks beginning at 5 weeks of age with PerT-GUS or native GUS and used micro-CT, radiographs, and quantitative histopathological analysis for assessment of bones. Micro-CT findings showed PerT-GUS treated mice had a significantly lower BMD. Histopathological analysis also showed reduced storage material and a more organized growth plate in PerT-GUS treated mice compared with native GUS treated mice. Long term treatment with PerT-GUS from birth up to 57 weeks also significantly improved bone lesions demonstrated by micro-CT, radiographs and quantitative histopathological assay. In conclusion, long-circulating PerT-GUS provides a significant impact to rescue of bone lesions and CNS involvement.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Diseases / diagnosis
  • Bone Diseases / etiology*
  • Bone Diseases / therapy*
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / pathology
  • Cervical Vertebrae / diagnostic imaging
  • Cervical Vertebrae / pathology
  • Enzyme Replacement Therapy*
  • Glucuronidase / administration & dosage
  • Glucuronidase / chemistry
  • Glucuronidase / therapeutic use*
  • Growth Plate / drug effects
  • Growth Plate / pathology
  • Knee Joint / diagnostic imaging
  • Knee Joint / pathology
  • Mice
  • Mucopolysaccharidosis VII / complications*
  • Mucopolysaccharidosis VII / diagnosis
  • Mucopolysaccharidosis VII / therapy*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / therapeutic use*
  • Tomography, X-Ray Computed


  • Recombinant Proteins
  • Glucuronidase