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Human Genetics

, Volume 121, Issue 1, pp 1–22 | Cite as

New therapeutic options for lysosomal storage disorders: enzyme replacement, small molecules and gene therapy

  • Michael BeckEmail author
Review

Abstract

During the last few years, much progress has been made in the treatment of lysosomal storage disorders. In the past, no specific therapy was available for the affected patients, and management consisted solely of supportive care and treatment of complications. Since enzyme replacement therapy has been successfully introduced for patients with Gaucher disease, this principle of treatment has been taken into consideration for other lysosomal storage disorders as well. Clinical trials could demonstrate the clinical benefit of this therapeutic principle in Fabry disease, mucopolysaccharidoses type I, II and VI and in Pompe disease. However, the usefulness of enzyme replacement therapy is limited due to the fact that a given enzyme preparation does not have beneficial effects on all aspects of a disorder in the same degree. Additionally, clinical studies have shown that many symptoms of a lysosomal storage disorder even after long-term treatment are no more reversible. A further novel therapeutic option for lysosomal storage disorders consists of the application of small molecules that either inhibit a key enzyme which is responsible for substrate synthesis (substrate deprivation) or act as a chaperone to increase the residual activity of the lysosomal enzyme (enzyme enhancing therapy). Various gene therapeutic techniques (in vivo and ex vivo technique) have been developed in order to administer the gene that is defective in a patient to the bloodstream or directly to the brain in order to overcome the blood–brain barrier. This review will give an insight into these newly developed therapeutic strategies and will discuss their advantages and limitations.

Keywords

Enzyme Replacement Therapy Fabry Disease Gauche Disease Pompe Disease Lysosomal Storage Disorder 
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.

Notes

Acknowledgments

Declaration of conflict of interest: the author has received unrestricted scientific grants from Shire Human Genetic Therapies, Genzyme Corp., Actelion Pharmaceuticals Ltd. and Biomarin Pharmaceutical Inc.

References

  1. Altarescu G, Hill S, Wiggs E, Jeffries N, Kreps C, Parker CC, Brady RO, Barton NW, Schiffmann R (2001) The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher’s disease. J Pediatr 138:539–547PubMedGoogle Scholar
  2. Amalfitano A, Bengur AR, Morse RP, Majure JM, Case LE, Veerling DL, Mackey J, Kishnani P, Smith W, McVie-Wylie A, Sullivan JA, Hoganson GE, Phillips JA III, Schaefer GB, Charrow J, Ware RE, Bossen EH, Chen YT (2001) Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genet Med 3:132–138PubMedGoogle Scholar
  3. An Y, Young SP, Kishnani PS, Millington DS, Amalfitano A, Corz D, Chen YT (2005) Glucose tetrasaccharide as a biomarker for monitoring the therapeutic response to enzyme replacement therapy for Pompe disease. Mol Genet Metab 85:247–254PubMedGoogle Scholar
  4. Andersson HC, Charrow J, Kaplan P, Mistry P, Pastores GM, Prakash-Cheng A, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ (2005) Individualization of long-term enzyme replacement therapy for Gaucher disease. Genet Med 7:105–110PubMedGoogle Scholar
  5. Aoki M, Takahashi Y, Miwa Y, Iida S, Sukegawa K, Horai T, Orii T, Kondo N (2001) Improvement of neurological symptoms by enzyme replacement therapy for Gaucher disease type IIIb. Eur J Pediatr 160:63–64PubMedGoogle Scholar
  6. Balfour-Lynn IM, Prasad SA, Laverty A, Whitehead BF, Dinwiddie R (1998) A step in the right direction: assessing exercise tolerance in cystic fibrosis. Pediatr Pulmonol 25:278–284PubMedGoogle Scholar
  7. Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC, Mankin HJ, Murray GJ, Parker RI, Argoff CE et al (1991) Replacement therapy for inherited enzyme deficiency-macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med 324:1464–1470PubMedCrossRefGoogle Scholar
  8. Beck M (2006) Galsulfase: enzyme-replacement therapy for mucopolysaccharidosis Type VI (Maroteaux–Lamy syndrome). Therapy 3:9–17Google Scholar
  9. Beck M, Ricci R, Widmer U, Dehout F, de Lorenzo AG, Kampmann C, Linhart A, Sunder-Plassmann G, Houge G, Ramaswami U, Gal A, Mehta A (2004) Fabry disease: overall effects of agalsidase alfa treatment. Eur J Clin Invest 34:838–844PubMedGoogle Scholar
  10. Beck M, Harmatz P, Giugliani R, Schwartz I, Guffon N, Sa Miranda MC, Teles EL, Wraith JE, Scarpa M, Berger KI, Swiedler SJ (2005) Follow-up extension study of a double-blind phase 3 clinical study of recombinant human Arylsulfatase B (rhASB) in patients with Mucopolysaccharidosis VI (MPS VI) (abstract). Eur J Hum Genet 13(Suppl 1):67Google Scholar
  11. Bembi B, Marchetti F, Guerci VI, Ciana G, Addobbati R, Grasso D, Barone R, Cariati R, Fernandez-Guillen L, Butters T, Pittis MG (2006) Substrate reduction therapy in the infantile form of Tay–Sachs disease. Neurology 66:278–280PubMedGoogle Scholar
  12. Bernier V, Lagace M, Bichet DG, Bouvier M (2004) Pharmacological chaperones: potential treatment for conformational diseases. Trends Endocrinol Metab 15:222–228PubMedGoogle Scholar
  13. Biffi A, De Palma M, Quattrini A, Del Carro U, Amadio S, Visigalli I, Sessa M, Fasano S, Brambilla R, Marchesini S, Bordignon C, Naldini L (2004) Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells. J Clin Invest 113:1118–1129PubMedGoogle Scholar
  14. Boot RG, Renkema GH, Verhoek M, Strijland A, Bliek J, de Meulemeester TM, Mannens MM, Aerts JM (1998) The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem 273:25680–25685PubMedGoogle Scholar
  15. Boot RG, Verhoek M, de Fost M, Hollak CE, Maas M, Bleijlevens B, van Breemen MJ, van Meurs M, Boven LA, Laman JD, Moran MT, Cox TM, Aerts JM (2004) Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention. Blood 103:33–39PubMedGoogle Scholar
  16. Boscaro F, Pieraccini G, la Marca G, Bartolucci G, Luceri C, Luceri F, Moneti G (2002) Rapid quantitation of globotriaosylceramide in human plasma and urine: a potential application for monitoring enzyme replacement therapy in Anderson–Fabry disease. Rapid Commun Mass Spectrom 16:1507–1514PubMedGoogle Scholar
  17. Brady RO, Tallman JF, Johnson WG, Gal AE, Leahy WR, Quirk JM, Dekaban AS (1973) Replacement therapy for inherited enzyme deficiency. Use of purified ceramidetrihexosidase in Fabry’s disease. N Engl J Med 289:9–14PubMedCrossRefGoogle Scholar
  18. Brinkman J, Wijburg FA, Hollak CE, Groener JE, Verhoek M, Scheij S, Aten J, Boot RG, Aerts JM (2005) Plasma chitotriosidase and CCL18: early biochemical surrogate markers in type B Niemann–Pick disease. J Inherit Metab Dis 28:13–20PubMedGoogle Scholar
  19. Brooks AI, Stein CS, Hughes SM, Heth J, McCray PM Jr, Sauter SL, Johnston JC, Cory-Slechta DA, Federoff HJ, Davidson BL (2002) Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors. Proc Natl Acad Sci USA 99:6216–6221PubMedGoogle Scholar
  20. Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ, Zimran A (2000) The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 160:2835–2843PubMedGoogle Scholar
  21. Choi EH, Zimmerman PA, Foster CB, Zhu S, Kumaraswami V, Nutman TB, Chanock SJ (2001) Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India. Genes Immun 2:248–253PubMedGoogle Scholar
  22. Ciron C, Desmaris N, Colle MA, Raoul S, Joussemet B, Verot L, Ausseil J, Froissart R, Roux F, Cherel Y, Ferry N, Lajat Y, Schwartz B, Vanier MT, Maire I, Tardieu M, Moullier P, Heard JM (2006) Gene therapy of the brain in the dog model of Hurler’s syndrome. Ann Neurol 60:204–213PubMedGoogle Scholar
  23. Cleeland CS, Gonin R, Hatfield AK, Edmonson JH, Blum RH, Stewart JA, Pandya KJ (1994) Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 330:592–596PubMedGoogle Scholar
  24. Cox T, Lachmann R, Hollak C, Aerts J, van Weely S, Hrebicek M, Platt F, Butters T, Dwek R, Moyses C, Gow I, Elstein D, Zimran A (2000) Novel oral treatment of Gaucher’s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 355:1481–1485PubMedGoogle Scholar
  25. Cox TM, Aerts JM, Andria G, Beck M, Belmatoug N, Bembi B, Chertkoff R, Vom Dahl S, Elstein D, Erikson A, Giralt M, Heitner R, Hollak C, Hrebicek M, Lewis S, Mehta A, Pastores GM, Rolfs A, Miranda MC, Zimran A (2003) The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement. J Inherit Metab Dis 26:513–526PubMedGoogle Scholar
  26. Crystal RG, Sondhi D, Hackett NR, Kaminsky SM, Worgall S, Stieg P, Souweidane M, Hosain S, Heier L, Ballon D, Dinner M, Wisniewski K, Kaplitt M, Greenwald BM, Howell JD, Strybing K, Dyke J, Voss H (2004) Clinical protocol. Administration of a replication-deficient adeno-associated virus gene transfer vector expressing the human CLN2 cDNA to the brain of children with late infantile neuronal ceroid lipofuscinosis. Hum Gene Ther 15:1131–1154PubMedGoogle Scholar
  27. De Palma M, Montini E, de Sio FR, Benedicenti F, Gentile A, Medico E, Naldini L (2005) Promoter trapping reveals significant differences in integration site selection between MLV and HIV vectors in primary hematopoietic cells. Blood 105:2307–2315PubMedGoogle Scholar
  28. Desmaris N, Verot L, Puech JP, Caillaud C, Vanier MT, Heard JM (2004) Prevention of neuropathology in the mouse model of Hurler syndrome. Ann Neurol 56:68–76PubMedGoogle Scholar
  29. Dhami R, Schuchman EH (2004) Mannose 6-phosphate receptor-mediated uptake is defective in acid sphingomyelinase-deficient macrophages: implications for Niemann–Pick disease enzyme replacement therapy. J Biol Chem 279:1526–1532PubMedGoogle Scholar
  30. Di Domenico C, Villani GR, Di Napoli D, Reyero EG, Lombardo A, Naldini L, Di Natale P (2005) Gene therapy for a mucopolysaccharidosis type I murine model with lentiviral-IDUA vector. Hum Gene Ther 16:81–90PubMedGoogle Scholar
  31. Elstein D, Hollak C, Aerts JM, van Weely S, Maas M, Cox TM, Lachmann RH, Hrebicek M, Platt FM, Butters TD, Dwek RA, Zimran A (2004) Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease. J Inherit Metab Dis 27:757–766PubMedGoogle Scholar
  32. Eng CM, Banikazemi M, Gordon RE, Goldman M, Phelps R, Kim L, Gass A, Winston J, Dikman S, Fallon JT, Brodie S, Stacy CB, Mehta D, Parsons R, Norton K, O’Callaghan M, Desnick RJ (2001a) A phase 1/2 clinical trial of enzyme replacement in Fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet 68:711–722Google Scholar
  33. Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ (2001b) Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry’s disease. N Engl J Med 345:9–16Google Scholar
  34. Erikson A, Astrom M, Mansson JE (1995) Enzyme infusion therapy of the Norrbottnian (type 3) Gaucher disease. Neuropediatrics 26:203–207PubMedGoogle Scholar
  35. Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J (2005) Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. N Engl J Med 352:2069–2081PubMedGoogle Scholar
  36. Fischl MA, Resnick L, Coombs R, Kremer AB, Pottage JC Jr, Fass RJ, Fife KH, Powderly WG, Collier AC, Aspinall RL et al (1994) The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3. J Acquir Immune Defic Syndr 7:139–147PubMedGoogle Scholar
  37. Follenzi A, Battaglia M, Lombardo A, Annoni A, Roncarolo MG, Naldini L (2004) Targeting lentiviral vector expression to hepatocytes limits transgene-specific immune response and establishes long-term expression of human antihemophilic factor IX in mice. Blood 103:3700–3709PubMedGoogle Scholar
  38. Fratantoni JC, Hall CW, Neufeld EF (1968) Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science 162:570–572PubMedGoogle Scholar
  39. Germain DP (2002) Fabry disease: recent advances in enzyme replacement therapy. Expert Opin Investig Drugs 11:1467–1476PubMedGoogle Scholar
  40. Ghosh P, Dahms NM, Kornfeld S (2003) Mannose 6-phosphate receptors: new twists in the tale. Nat Rev Mol Cell Biol 4:202–212PubMedGoogle Scholar
  41. Ginsel LA, Fransen JA (1991) Mannose 6-phosphate receptor independent targeting of lysosomal enzymes (a mini-review). Cell Biol Int Rep 15:1167–1173PubMedGoogle Scholar
  42. Ginzburg L, Kacher Y, Futerman AH (2004) The pathogenesis of glycosphingolipid storage disorders. Semin Cell Dev Biol 15:417–431PubMedGoogle Scholar
  43. Goker-Alpan O, Schiffmann R, Park JK, Stubblefield BK, Tayebi N, Sidransky E (2003) Phenotypic continuum in neuronopathic Gaucher disease: an intermediate phenotype between type 2 and type 3. J Pediatr 143:273–276PubMedGoogle Scholar
  44. Grabowski GA (2005) Recent clinical progress in Gaucher disease. Curr Opin Pediatr 17:519–524PubMedGoogle Scholar
  45. Grabowski GA, Barton NW, Pastores G, Dambrosia JM, Banerjee TK, McKee MA, Parker C, Schiffmann R, Hill SC, Brady RO (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
  46. Grabowski GA, Leslie N, Wenstrup R (1998) Enzyme therapy for Gaucher disease: the first 5 years. Blood Rev 12:115–133PubMedGoogle Scholar
  47. Greiner-Tollersrud OK, Berg T (2005) Lysosomal storage disorders. In: Saftig P (ed) Lysosomes, 1st edn. Landes Bioscience, Georgetown, pp 60–73Google Scholar
  48. Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, Radford I, Villeval JL, Fraser CC, Cavazzana-Calvo M, Fischer A (2003) A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 348:255–256PubMedGoogle Scholar
  49. Hackett NR, Redmond DE, Sondhi D, Giannaris EL, Vassallo E, Stratton J, Qiu J, Kaminsky SM, Lesser ML, Fisch GS, Rouselle SD, Crystal RG (2005) Safety of direct administration of AAV2(CU)hCLN2, a candidate treatment for the central nervous system manifestations of late infantile neuronal ceroid lipofuscinosis, to the brain of rats and nonhuman primates. Hum Gene Ther 16:1484–1503PubMedGoogle Scholar
  50. Harmatz P, Giugliani R, Schwartz I, Guffon N, Sa Miranda MC, Teles EL, Wraith E, Beck M, Hopwood J, Swiedler SJ (2004a) A phase 3, randomized, double-blind, placebo-controlled, multicenter, multinational clinical study of recombinant human N-acetylgalactosamine 4-sulfatase (rhASB) in patients with Mucopolysaccharidosis VI (MPS VI) (abstract). The American Society of Human Genetics, Toronto, pp 71Google Scholar
  51. Harmatz P, Whitley CB, Waber L, Pais R, Steiner R, Plecko B, Kaplan P, Simon J, Butensky E, Hopwood JJ (2004b) Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux–Lamy syndrome). J Pediatr 144:574–580Google Scholar
  52. Harmatz P, Ketteridge D, Giugliani R, Guffon N, Teles EL, Miranda MC, Yu ZF, Swiedler SJ, Hopwood JJ (2005) Direct comparison of measures of endurance, mobility, and joint function during enzyme-replacement therapy of mucopolysaccharidosis VI (Maroteaux–Lamy syndrome): results after 48 weeks in a phase 2 open-label clinical study of recombinant human N-acetylgalactosamine 4-sulfatase. Pediatrics 115:e681–e689PubMedGoogle Scholar
  53. Heitner R, Elstein D, Aerts J, Weely S, Zimran A (2002) Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease. Blood Cells Mol Dis 28:127–133PubMedGoogle Scholar
  54. Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 93:1288–1292PubMedCrossRefGoogle Scholar
  55. Hollak CE, Evers L, Aerts JM, van Oers MH (1997) Elevated levels of M-CSF, sCD14 and IL8 in type 1 Gaucher disease. Blood Cells Mol Dis 23:201–212PubMedGoogle Scholar
  56. van den Hout HM, Hop W, van Diggelen OP, Smeitink JA, Smit GP, Poll-The BT, Bakker HD, Loonen MC, de Klerk JB, Reuser AJ, van der Ploeg AT (2003) The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatrics 112:332–340PubMedGoogle Scholar
  57. Huntington JA (2003) Mechanisms of glycosaminoglycan activation of the serpins in hemostasis. J Thromb Haemost 1:1535–1549PubMedGoogle Scholar
  58. Imrie J, Vijayaraghaven S, Whitehouse C, Harris S, Heptinstall L, Church H, Cooper A, Besley GT, Wraith JE (2002) Niemann–Pick disease type C in adults. J Inherit Metab Dis 25:491–500PubMedGoogle Scholar
  59. Jeyakumar M, Butters TD, Cortina-Borja M, Hunnam V, Proia RL, Perry VH, Dwek RA, Platt FM (1999) Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. Proc Natl Acad Sci USA 96:6388–6393PubMedGoogle Scholar
  60. Jeyakumar M, Thomas R, Elliot-Smith E, Smith DA, van der Spoel AC, d’Azzo A, Perry VH, Butters TD, Dwek RA, Platt FM (2003) Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain 126:974–987PubMedGoogle Scholar
  61. Johnson WG, Desnick RJ, Long DM, Sharp M, Krivit W, Brady R (1973) Intravenous injection of purified hexosaminidase A into patients with Tay–Sachs disease. In: Desnick RJ, Bernlohr R, Krivit W (eds) Enzyme therapy in genetic diseases. Alan R. Liss, New York, pp 120Google Scholar
  62. 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 361:1608–1613PubMedGoogle Scholar
  63. Kakkis ED, Muenzer J, Tiller GE, Waber L, John Belmont J, Merry Passage M, Izykowski B, Phillips J, Doroshow R, Irv Walot I, Richard Hoft R, Yu KT, Okazaki S, Dave Lewis D, Ralph Lachman R, Jerry N, Thompson JN, Neufeld FE (2001) Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 344:182–188PubMedGoogle Scholar
  64. Kay GW, Palmer DN, Rezaie P, Cooper JD (2006) Activation of non-neuronal cells within the prenatal developing brain of sheep with neuronal ceroid lipofuscinosis. Brain Pathol 16:110–116PubMedGoogle Scholar
  65. Kishnani PS, Howell RR (2004) Pompe disease in infants and children. J Pediatr 144:S35–S43PubMedGoogle Scholar
  66. Kitagawa T, Ishige N, Suzuki K, Owada M, Ohashi T, Kobayashi M, Eto Y, Tanaka A, Mills K, Winchester B, Keutzer J (2005) Non-invasive screening method for Fabry disease by measuring globotriaosylceramide in whole urine samples using tandem mass spectrometry. Mol Genet Metab 85:196–202PubMedGoogle Scholar
  67. Kornfeld S, Mellman I (1989) The biogenesis of lysosomes. Annu Rev Cell Biol 5:483–525PubMedGoogle Scholar
  68. Krivit W, Peters C, Shapiro EG (1999) Bone marrow transplantation as effective treatment of central nervous system disease in globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux–Lamy, and Sly syndromes, and Gaucher disease type III. Curr Opin Neurol 12:167–176PubMedGoogle Scholar
  69. Lachmann RH, Te Vruchte D, Lloyd-Evans E, Reinkensmeier G, Sillence DJ, Fernandez-Guillen L, Dwek RA, Butters TD, Cox TM, Platt FM (2004) Treatment with miglustat reverses the lipid-trafficking defect in Niemann–Pick disease type C. Neurobiol Dis 16:654–658PubMedGoogle Scholar
  70. Lee K, Jin X, Zhang K, Copertino L, Andrews L, Baker-Malcolm J, Geagan L, Qiu H, Seiger K, Barngrover D, McPherson JM, Edmunds T (2003) A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease. Glycobiology 13:305–313PubMedGoogle Scholar
  71. Li C, Ziegler RJ, Cherry M, Lukason M, Desnick RJ, Yew NS, Cheng SH (2002) Adenovirus-transduced lung as a portal for delivering alpha-galactosidase a into systemic circulation for Fabry disease. Mol Ther 5:745–754PubMedGoogle Scholar
  72. Linthorst GE, Hollak CE, Donker-Koopman WE, Strijland A, Aerts JM (2004) Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 66:1589–1595PubMedGoogle Scholar
  73. Malm G, Ringden O, Winiarski J, Grondahl E, Uyebrant P, Eriksson U, Hakansson H, Skjeldal O, Mansson JE (1996) Clinical outcome in four children with metachromatic leukodystrophy treated by bone marrow transplantation. Bone Marrow Transplant 17:1003–1008PubMedGoogle Scholar
  74. Mango RL, Xu L, Sands MS, Vogler C, Seiler G, Schwarz T, Haskins ME, Ponder KP (2004) Neonatal retroviral vector-mediated hepatic gene therapy reduces bone, joint, and cartilage disease in mucopolysaccharidosis VII mice and dogs. Mol Genet Metab 82:4–19PubMedGoogle Scholar
  75. Masoud M, Rudensky B, Elstein D, Zimran A (2002) Chitotriosidase deficiency in survivors of Candida sepsis. Blood Cells Mol Dis 29:116–118PubMedGoogle Scholar
  76. Matzner U, Gieselmann V (2005) Gene therapy of metachromatic leukodystrophy. Expert Opin Biol Ther 5:55–65PubMedGoogle Scholar
  77. Mehta A, Ricci R, Widmer U, Dehout F, De Garcia Lorenzo A, Kampmann C, Linhart A, Sunder-Plassmann G, Ries M, Beck M (2004) Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry outcome survey. Eur J Clin Invest 34:236–242PubMedGoogle Scholar
  78. Meikle PJ, Grasby DJ, Dean CJ, Lang DL, Bockmann M, Whittle AM, Fietz MJ, Simonsen H, Fuller M, Brooks DA, Hopwood JJ (2006) Newborn screening for lysosomal storage disorders. Mol Genet Metab 88:307–314PubMedGoogle Scholar
  79. Mills K, Vellodi A, Morris P, Cooper D, Morris M, Young E, Winchester B (2004) Monitoring the clinical and biochemical response to enzyme replacement therapy in three children with Fabry disease. Eur J Pediatr 163:595–603PubMedGoogle Scholar
  80. Moller HJ, Fost Md, Aerts H, Hollak C, Moestrup SK (2004) Plasma level of the macrophage-derived soluble CD163 is increased and positively correlates with severity in Gaucher’s disease. Eur J Haematol 72:135–139PubMedGoogle Scholar
  81. Muenzer J (2004) The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr 144:S27–S34PubMedGoogle Scholar
  82. Muenzer J, Towle D, Calikoglu M, McCandllles S (2002) A phase I/II clinical study evaluating the safety and clinical activity of enzyme replacement therapy in Mucopolysaccharidosis II (Hunter syndrome). Am J Hum Genet 71(Suppl):582Google Scholar
  83. Muenzer J, Wraight EP, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Calikoglu M, Vijayaraghavan S, Puga A, Ulbrich B, Shinawi M, Cleary M, Wendt S (2005) The phase II/III I2S enzyme replacement (ERT) clinical trial results for MPS II. 55th Annual Meeting American Society of Human Genetics, Salt Lake City, UtahGoogle Scholar
  84. Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga A, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A (2006) A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med 8:465–473PubMedCrossRefGoogle Scholar
  85. Ohmi K, Greenberg DS, Rajavel KS, Ryazantsev S, Li HH, Neufeld EF (2003) Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB. Proc Natl Acad Sci USA 100:1902–1907PubMedGoogle Scholar
  86. Orii KO, Grubb JH, Vogler C, Levy B, Tan Y, Markova K, Davidson BL, Mao Q, Orii T, Kondo N, Sly WS (2005) Defining the pathway for Tat-mediated delivery of beta-glucuronidase in cultured cells and MPS VII mice. Mol Ther 12:345–352PubMedGoogle Scholar
  87. Orvisky E, Sidransky E, McKinney CE, Lamarca ME, Samimi R, Krasnewich D, Martin BM, Ginns EI (2000) Glucosylsphingosine accumulation in mice and patients with type 2 Gaucher disease begins early in gestation. Pediatr Res 48:233–237PubMedGoogle Scholar
  88. Passini MA, Dodge JC, Bu J, Yang W, Zhao Q, Sondhi D, Hackett NR, Kaminsky SM, Mao Q, Shihabuddin LS, Cheng SH, Sleat DE, Stewart GR, Davidson BL, Lobel P, Crystal RG (2006) Intracranial delivery of CLN2 reduces brain pathology in a mouse model of classical late infantile neuronal ceroid lipofuscinosis. J Neurosci 26:1334–1342PubMedGoogle Scholar
  89. Pastores GM, Barnett NL (2003) Substrate reduction therapy: miglustat as a remedy for symptomatic patients with Gaucher disease type 1. Expert Opin Investig Drugs 12:273–281PubMedGoogle Scholar
  90. Pelled D, Shogomori H, Futerman AH (2000) The increased sensitivity of neurons with elevated glucocerebroside to neurotoxic agents can be reversed by imiglucerase. J Inherit Metab Dis 23:175–184PubMedGoogle Scholar
  91. Peters C, Steward CG (2003) Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant 31:229–239PubMedGoogle Scholar
  92. Poll LW, Koch JA, vom Dahl S, Willers R, Scherer A, Boerner D, Niederau C, Haussinger D, Modder U (2001) Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results. Skeletal Radiol 30:496–503PubMedGoogle Scholar
  93. Poll LW, Maas M, Terk MR, Roca-Espiau M, Bembi B, Ciana G, Weinreb NJ (2002) Response of Gaucher bone disease to enzyme replacement therapy. Br J Radiol 75:A25–A36PubMedGoogle Scholar
  94. Prows CA, Sanchez N, Daugherty C, Grabowski GA (1997) Gaucher disease: enzyme therapy in the acute neuronopathic variant. Am J Med Genet 71:16–21PubMedGoogle Scholar
  95. Raben N, Danon M, Gilbert AL, Dwivedi S, Collins B, Thurberg BL, Mattaliano RJ, Nagaraju K, Plotz PH (2003) Enzyme replacement therapy in the mouse model of Pompe disease. Mol Genet Metab 80:159–169PubMedGoogle Scholar
  96. Radin NS (1996) Treatment of Gaucher disease with an enzyme inhibitor. Glycoconj J 13:153–157PubMedGoogle Scholar
  97. Randall DR, Sinclair GB, Colobong KE, Hetty E, Clarke LA (2006) Heparin cofactor II–thrombin complex in MPS I: a biomarker of MPS disease. Mol Genet Metab 88:235–243PubMedGoogle Scholar
  98. Rosenberg M, Kingma W, Fitzpatrick MA, Richards SM (1999) Immunosurveillance of alglucerase enzyme therapy for Gaucher patients: induction of humoral tolerance in seroconverted patients after repeat administration. Blood 93:2081–2088PubMedGoogle Scholar
  99. Sands MS, Davidson BL (2006) Gene therapy for lysosomal storage diseases. Mol Ther 13:839–849PubMedGoogle Scholar
  100. Savas PS, Hemsley KM, Hopwood JJ (2004) Intracerebral injection of sulfamidase delays neuropathology in murine MPS-IIIA. Mol Genet Metab 82:273–285PubMedGoogle Scholar
  101. Sawkar AR, Cheng WC, Beutler E, Wong CH, Balch WE, Kelly JW (2002) Chemical chaperones increase the cellular activity of N370S beta-glucosidase: a therapeutic strategy for Gaucher disease. Proc Natl Acad Sci USA 99:15428–15433PubMedGoogle Scholar
  102. Schiffmann R, Heyes MP, Aerts JM, Dambrosia JM, Patterson MC, DeGraba T, Parker CC, Zirzow GC, Oliver K, Tedeschi G, Brady RO, Barton NW (1997) Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher’s disease. Ann Neurol 42:613–621PubMedGoogle Scholar
  103. Schiffmann R, Kopp JB, Austin HA III, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO (2001) Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 285:2743–2749PubMedGoogle Scholar
  104. Simonaro CM, D’Angelo M, Haskins ME, Schuchman EH (2005) Joint and bone disease in mucopolysaccharidoses VI and VII: identification of new therapeutic targets and biomarkers using animal models. Pediatr Res 57:701–707PubMedGoogle Scholar
  105. Sondhi D, Peterson DA, Giannaris EL, Sanders CT, Mendez BS, De B, Rostkowski AB, Blanchard B, Bjugstad K, Sladek JR Jr, Redmond DE Jr, Leopold PL, Kaminsky SM, Hackett NR, Crystal RG (2005) AAV2-mediated CLN2 gene transfer to rodent and non-human primate brain results in long-term TPP-I expression compatible with therapy for LINCL. Gene Ther 12:1618–1632PubMedGoogle Scholar
  106. Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit W, Kurtzberg J (2004) Cord-blood transplants from unrelated donors in patients with Hurler’s syndrome. N Engl J Med 350:1960–1969PubMedGoogle Scholar
  107. Swiedler SJ, Beck M, Bajbouj M, Giugliani R, Schwartz I, Harmatz P, Wraith JE, Roberts J, Ketteridge D, Hopwood JJ, Guffon N, Sa Miranda MC, Teles EL, Berger KI, Piscia-Nichols C (2005) Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with Mucopolysaccharidosis VI (Maroteaux–Lamy syndrome). Am J Med Genet A 134A:144–150PubMedGoogle Scholar
  108. Tierney M, Pottage J, Kessler H, Fischl M, Richman D, Merigan T, Powderly W, Smith S, Karim A, Sherman J et al (1995) The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases. J Acquir Immune Defic Syndr Hum Retrovirol 10:549–553PubMedCrossRefGoogle Scholar
  109. Tropak MB, Reid SP, Guiral M, Withers SG, Mahuran D (2004) Pharmacological enhancement of beta-hexosaminidase activity in fibroblasts from adult Tay–Sachs and Sandhoff Patients. J Biol Chem 279:13478–13487PubMedGoogle Scholar
  110. Van den Hout JM, Kamphoven JH, Winkel LP, Arts WF, De Klerk JB, Loonen MC, Vulto AG, Cromme-Dijkhuis A, Weisglas-Kuperus N, Hop W, Van Hirtum H, Van Diggelen OP, Boer M, Kroos MA, Van Doorn PA, Van der Voort E, Sibbles B, Van Corven EJ, Brakenhoff JP, Van Hove J, Smeitink JA, de Jong G, Reuser AJ, Van der Ploeg AT (2004) Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics 113:e448–e457PubMedGoogle Scholar
  111. Van der Ploeg AT, Kroos MA, Willemsen R, Brons NH, Reuser AJ (1991) Intravenous administration of phosphorylated acid alpha-glucosidase leads to uptake of enzyme in heart and skeletal muscle of mice. J Clin Invest 87:513–518PubMedGoogle Scholar
  112. Wada R, Tifft CJ, Proia RL (2000) Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. Proc Natl Acad Sci USA 97:10954–10959PubMedGoogle Scholar
  113. Wasserstein MP, Desnick RJ, Schuchman EH, Hossain S, Wallenstein S, Lamm C, McGovern MM (2004) The natural history of type B Niemann–Pick disease: results from a 10-year longitudinal study. Pediatrics 114:e672–e677PubMedGoogle Scholar
  114. Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W, Ertl G, Knoll A, Wanner C, Strotmann JM (2003) Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation 108:1299–1301PubMedGoogle Scholar
  115. Wenk J, Hille A, von Figura K (1991) Quantitation of Mr 46000 and Mr 300000 mannose 6-phosphate receptors in human cells and tissues. Biochem Int 23:723–731PubMedGoogle Scholar
  116. Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, Desnick RJ, Germain DP (2004) Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 75:65–74PubMedGoogle Scholar
  117. Winchester BG (2001) Lysosomal membrane proteins. Eur J Paediatr Neurol 5(Suppl A):11–19PubMedGoogle Scholar
  118. Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Swiedler SJ, Kakkis ED, Braakman T, Chadbourne E, Walton-Bowen K, Cox GF (2004) Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-l-iduronidase (laronidase). J Pediatr 144:581–588PubMedGoogle Scholar
  119. Xia H, Mao Q, Davidson BL (2001) The HIV Tat protein transduction domain improves the biodistribution of beta-glucuronidase expressed from recombinant viral vectors. Nat Biotechnol 19:640–644PubMedGoogle Scholar
  120. Yam GH, Zuber C, Roth J (2005) A synthetic chaperone corrects the trafficking defect and disease phenotype in a protein misfolding disorder. FASEB J 19:12–18PubMedGoogle Scholar
  121. Zervas M, Somers KL, Thrall MA, Walkley SU (2001) Critical role for glycosphingolipids in Niemann–Pick disease type C. Curr Biol 11:1283–1287PubMedGoogle Scholar
  122. Zheng Y, Rozengurt N, Ryazantsev S, Kohn DB, Satake N, Neufeld EF (2003) Treatment of the mouse model of mucopolysaccharidosis I with retrovirally transduced bone marrow. Mol Genet Metab 79:233–244PubMedGoogle Scholar

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© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Children HospitalUniversity of MainzMainzGermany

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