Journal of Inherited Metabolic Disease

, Volume 33, Issue 5, pp 611–617 | Cite as

Early initiation of enzyme replacement therapy improves metabolic correction in the brain tissue of aspartylglycosaminuria mice

  • Ulla Dunder
  • Pirjo Valtonen
  • Eira Kelo
  • Ilkka MononenEmail author
Original Article


Aspartylglycosaminuria (AGU) is a lysosomal storage disease caused by deficient activity of glycosylasparaginase (AGA), and characterized by motor and mental retardation. Enzyme replacement therapy (ERT) in adult AGU mice with AGA removes the accumulating substance aspartylglucosamine from and reverses pathology in many somatic tissues, but has only limited efficacy in the brain tissue of the animals. In the current work, ERT of AGU mice was initiated at the age of 1 week with three different dosage schedules of recombinant glycosylasparaginase. The animals received either 3.4 U of AGA/kg every second day for 2 weeks (Group 1), 1.7 U/kg every second day for 9 days followed by an enzyme injection once a week for 4 weeks (Group 2) or 17 U/kg at the age of 7 and 9 days (Group 3). In the Group 1 and Group 3 mice, ERT reduced the amount of aspartylglucosamine by 34 and 41% in the brain tissue, respectively. No therapeutic effect was observed in the brain tissue of Group 2 mice. As in the case of adult AGU mice, the AGA therapy was much more effective in the somatic tissues than in the brain tissue of the newborn AGU mice. The combined evidence demonstrates that a high dose ERT with AGA in newborn AGU mice is up to twofold more effective in reducing the amount of the accumulated storage material from the brain tissue than ERT in adult AGU animals, indicating the importance of early detection and treatment of the disease.


Enzyme Replacement Therapy Fabry Disease Somatic Tissue Lysosomal Storage Disease Enzyme Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.







Blood–brain barrier




Central nervous system


Enzyme replacement therapy







This work was financially supported by grants from The Sigrid Juselius Foundation (I.M.), the Pediatric Research Foundation (Ulla Hjelt Fund) (I.M.), and Kuopio University Hospital (EVO grant #5100).


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Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Ulla Dunder
    • 1
    • 2
  • Pirjo Valtonen
    • 2
  • Eira Kelo
    • 2
  • Ilkka Mononen
    • 3
    Email author
  1. 1.Eastern Finland Laboratory CentreKuopioFinland
  2. 2.Clinical ChemistryUniversity of KuopioKuopioFinland
  3. 3.Department of Clinical Chemistry and HematologyUniversity of Turku and TUCH LaboratoriesTurkuFinland

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