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 Mononen
Original Article

Abstract

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.

Abbreviations

AGA

Glycosylasparaginase

AGU

Aspartylglycosaminuria

BBB

Blood–brain barrier

GlcNAc-Asn

Aspartylglucosamine

CNS

Central nervous system

ERT

Enzyme replacement therapy

M-6-P

Mannose-6-phosphate

MSP

Mucopolysaccharidosis

Reference

  1. Arvio M, Autio S, Mononen T (1997) Clinical manifestations of aspartylglycosaminuria. In: Mononen I, Aronson NN (eds) Lysosomal storage disease: aspartylglycosaminuria. R.G.Landes/Springer, Austin, pp 19–28Google Scholar
  2. Aula P, Jalanko A, Peltonen L (2001) Aspartylglucosaminuria. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease I–VII. McGraw-Hill, New York, pp 3535–3550Google Scholar
  3. Barton NW, Brady RO, Dambrosia JM et al (1991) Replacement therapy for inherited enzyme deficiency–macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med 324:1464–1470CrossRefPubMedGoogle Scholar
  4. Bielicki J, Crawley AC, Davey RC, Varnai JC, Hopwood JJ (1999) Advantages of using same species enzyme for replacement therapy in a feline model of mucopolysaccharidosis type VI. J Biol Chem 274:36335–36343CrossRefPubMedGoogle Scholar
  5. Bijvoet AG, Van HH, Kroos MA et al (1999) Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II. Hum Mol Genet 8:2145–2153CrossRefPubMedGoogle Scholar
  6. Blanz J, Stroobants S, Lullmann-Rauch R et al (2008) Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in alpha-mannosidosis mice. Hum Mol Genet 17:3437–3445CrossRefPubMedGoogle Scholar
  7. Bou-Gharios G, Abraham D, Olsen I (1993) Lysosomal storage diseases: mechanisms of enzyme replacement therapy. Histochem J 25:593–605CrossRefPubMedGoogle Scholar
  8. Brooks DA, Kakavanos R, Hopwood JJ (2003) Significance of immune response to enzyme-replacement therapy for patients with a lysosomal storage disorder. Trends Mol Med 9:450–453CrossRefPubMedGoogle Scholar
  9. Byers S, Crawley AC, Brumfield LK, Nuttall JD, Hopwood JJ (2000) Enzyme replacement therapy in a feline model of MPS VI: modification of enzyme structure and dose frequency. Pediatr Res 47:743–749CrossRefPubMedGoogle Scholar
  10. Crawley AC, Niedzielski KH, Isaac EL, Davey RC, Byers S, Hopwood JJ (1997) Enzyme replacement therapy from birth in a feline model of mucopolysaccharidosis type VI. J Clin Invest 99:651–662CrossRefPubMedGoogle Scholar
  11. Desnick RJ, Brady R, Barranger J et al (2003) Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138:338–346PubMedGoogle Scholar
  12. Dunder U, Kaartinen V, Valtonen P et al (2000) Enzyme replacement therapy in a mouse model of aspartylglycosaminuria. FASEB J 14:361–367PubMedGoogle Scholar
  13. Grabowski GA, Barton NW, Pastores G et al (1995) Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med 122:33–39PubMedGoogle Scholar
  14. Grubb JH, Vogler C, Levy B, Galvin N, Tan Y, Sly WS (2008) Chemically modified beta-glucuronidase crosses blood-brain barrier and clears neuronal storage in murine mucopolysaccharidosis VII. Proc Natl Acad Sci USA 105:2616–2621CrossRefPubMedGoogle Scholar
  15. Harmatz P, Giugliani R, Schwartz IV et al (2008) Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase. Mol Genet Metab 94:469–475CrossRefPubMedGoogle Scholar
  16. Kaartinen V, Mononen I (1990a) Detection of aspartylglycosaminuria using urine specimens recovered from absorbent filter paper. Clin Chim Acta 191:15–20CrossRefPubMedGoogle Scholar
  17. Kaartinen V, Mononen I (1990b) Assay of aspartylglycosylaminase by high-performance liquid chromatography. Anal Biochem 190:98–101CrossRefPubMedGoogle Scholar
  18. Kaartinen V, Williams JC, Tomich J, Yates JR III, Hood LE, Mononen I (1991) Glycosaparaginase from human leukocytes. Inactivation and covalent modification with diazo-oxonorvaline. J Biol Chem 266:5860–5869PubMedGoogle Scholar
  19. Kaartinen V, Mononen I, Voncken JW, Noronkoski T, Gonzalez-Gomez I, Heisterkamp N, Groffen J (1996) A mouse model for the human lysosomal disease aspartylglycosaminuria. Nat Med 2:1375–1378CrossRefPubMedGoogle Scholar
  20. Kakavanos R, Turner CT, Hopwood JJ, Kakkis ED, Brooks DA (2003) Immune tolerance after long-term enzyme-replacement therapy among patients who have mucopolysaccharidosis I. Lancet 361:1608–1613CrossRefPubMedGoogle Scholar
  21. Kakkis ED, McEntee MF, Schmidtchen A et al (1996) Long-term and high-dose trials of enzyme replacement therapy in the canine model of mucopolysaccharidosis I. Biochem Mol Med 58:156–167CrossRefPubMedGoogle Scholar
  22. Katzin LW, Amato AA (2008) Pompe disease: a review of the current diagnosis and treatment recommendations in the era of enzyme replacement therapy. J Clin Neuromuscul Dis 9:421–431CrossRefPubMedGoogle Scholar
  23. Kelo E, Dunder U, Mononen I (2005) Massive accumulation of Man2GlcNAc2-Asn in nonneuronal tissues of glycosylasparaginase-deficient mice and its removal by enzyme replacement therapy. Glycobiology 15:79–85CrossRefPubMedGoogle Scholar
  24. Lidove O, Joly D, Barbey F et al (2007) Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature. Int J Clin Pract 61:293–302CrossRefPubMedGoogle Scholar
  25. Matzner U, Herbst E, Hedayati KK et al (2005) Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy. Hum Mol Genet 14:1139–1152CrossRefPubMedGoogle Scholar
  26. Matzner U, Lullmann-Rauch R, Stroobants S et al (2009) Enzyme replacement improves ataxic gait and central nervous system histopathology in a mouse model of metachromatic leukodystrophy. Mol Ther 17:600–606CrossRefPubMedGoogle Scholar
  27. Mononen I, Aronson NN Jr (1997) Lysosomal storage disease: aspartylglycosaminuria. R.G.Landes/Springer, AustinGoogle Scholar
  28. Mononen IT, Kaartinen VM, Williams JC (1993) A fluorometric assay for glycosylasparaginase activity and detection of aspartylglycosaminuria. Anal Biochem 208:372–374CrossRefPubMedGoogle Scholar
  29. Mononen I, Heisterkamp N, Dunder U, Romppanen EL, Noronkoski T, Kuronen I, Groffen J (1995) Recombinant glycosylasparaginase and in vitro correction of aspartylglycosaminuria. FASEB J 9:428–433PubMedGoogle Scholar
  30. Porto C, Cardone M, Fontana F et al (2009) The pharmacological chaperone N-butyldeoxynojirimycin enhances enzyme replacement therapy in Pompe disease fibroblasts. Mol Ther 17:964–971CrossRefPubMedGoogle Scholar
  31. Roces DP, Lullmann-Rauch R et al (2004) Efficacy of enzyme replacement therapy in alpha-mannosidosis mice: a preclinical animal study. Hum Mol Genet 13:1979–1988CrossRefPubMedGoogle Scholar
  32. Shull RM, Kakkis ED, McEntee MF, Kania SA, Jonas AJ, Neufeld EF (1994) Enzyme replacement in a canine model of Hurler syndrome. Proc Natl Acad Sci USA 91:12937–12941CrossRefPubMedGoogle Scholar
  33. Sifuentes M, Doroshow R, Hoft R et al (2007) A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years. Mol Genet Metab 90:171–180CrossRefPubMedGoogle Scholar
  34. Sly WS (2000) The missing link in lysosomal enzyme targeting. J Clin Invest 105:563–564CrossRefPubMedGoogle Scholar
  35. Stewart K, Brown OA, Morelli AE et al (1997) Uptake of alpha-(L)-iduronidase produced by retrovirally transduced fibroblasts into neuronal and glial cells in vitro. Gene Ther 4:63–75CrossRefPubMedGoogle Scholar
  36. Turner CT, Hopwood JJ, Brooks DA (2000) Enzyme replacement therapy in mucopolysaccharidosis I: altered distribution and targeting of alpha-L-iduronidase in immunized rats. Mol Genet Metab 69:277–285CrossRefPubMedGoogle Scholar
  37. Urayama A, Grubb JH, Sly WS, Banks WA (2004) Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier. Proc Natl Acad Sci USA 101:12658–12663CrossRefPubMedGoogle Scholar
  38. Urayama A, Grubb JH, Sly WS, Banks WA (2008) Mannose 6-phosphate receptor-mediated transport of sulfamidase across the blood-brain barrier in the newborn mouse. Mol Ther 16:1261–1266CrossRefPubMedGoogle Scholar
  39. Vogler C, Sands MS, Levy B, Galvin N, Birkenmeier EH, Sly WS (1996) Enzyme replacement with recombinant beta-glucuronidase in murine mucopolysaccharidosis type VII: impact of therapy during the first six weeks of life on subsequent lysosomal storage, growth, and survival. Pediatr Res 39:1050–1054CrossRefPubMedGoogle Scholar
  40. Vogler C, Levy B, Grubb JH et al (2005) Overcoming the blood-brain barrier with high-dose enzyme replacement therapy in murine mucopolysaccharidosis VII. Proc Natl Acad Sci USA 102:14777–14782CrossRefPubMedGoogle Scholar
  41. Wang D, Bonten EJ, Yogalingam G, Mann L, d'Azzo A (2005) Short-term, high dose enzyme replacement therapy in sialidosis mice. Mol Genet Metab 85:181–189CrossRefPubMedGoogle Scholar
  42. Wraith JE (2008) Enzyme replacement therapy with idursulfase in patients with mucopolysaccharidosis type II. Acta Paediatr Suppl 97:76–78CrossRefPubMedGoogle Scholar
  43. Wraith JE, Clarke LA, Beck M et al (2004) Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr 144:581–588CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Ulla Dunder
    • 1
    • 2
  • Pirjo Valtonen
    • 2
  • Eira Kelo
    • 2
  • Ilkka Mononen
    • 3
  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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