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CC BY-NC-ND 4.0 · Journal of Child Science 2018; 08(01): e156-e162
DOI: 10.1055/s-0038-1667346
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Causal Therapies in Mucopolysaccharidoses: Enzyme Replacement Therapy

Ara Vartanyan
1   School of Medicine, Saint Louis University, St. Louis, Missouri, United States
,
Adriana M. Montaño
2   Department of Pediatrics, School of Medicine, Saint Louis University, St. Louis, Missouri, United States
3   Department of Biochemistry and Molecular Biology, School of Medicine, Saint Louis University, St. Louis, Missouri, United States
› Author Affiliations
Further Information

Publication History

26 January 2018

19 April 2018

Publication Date:
03 October 2018 (online)

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Abstract

Enzyme replacement therapy (ERT) for mucopolysaccharidoses (MPS) is the treatment of choice for patients, since it specifically addresses the underlying cause of the disease. Intravenous weekly infusions of recombinant enzymes for MPS I, II, IVA, VI, and VII have proven to be safe and efficacious for somatic symptoms. ERT has been shown to decrease urinary glycosaminoglycan levels and organomegaly, while improving stamina of patients, respiratory function, and quality of life. Although early administration of ERT optimizes outcomes, adult patients still benefit from treatment. ERT has been successfully used as combination therapy with hematopoietic stem cell transplant for patients with MPS I and MPS II, improving patient's cognitive outcomes. Although patients can receive benefit from ERT, current challenges include lack of improvement of neurological manifestations, limited effect on bone disease, development of immune response toward the infused enzyme, and high cost. We will discuss the milestones achieved by intravenous ERT for MPS diseases as well as the current challenges.

Keywords

enzyme replacement therapy - mucopolysaccharidoses - blood–brain barrier - skeletal disease
 

  • References

  • 1 Neufeld E, Muenzer J. The Mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D. . eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001
    Google Scholar
  • 2 Grubb JH, Vogler C, Sly WS. New strategies for enzyme replacement therapy for lysosomal storage diseases. Rejuvenation Res 2010; 13 (2–3): 229-236
    CrossrefPubMedGoogle Scholar
  • 3 Wraith EJ, Hopwood JJ, Fuller M, Meikle PJ, Brooks DA. Laronidase treatment of mucopolysaccharidosis I. BioDrugs 2005; 19 (01) 1-7
    CrossrefPubMedGoogle Scholar
  • 4 Taylor JA, Gibson GJ, Brooks DA, Hopwood JJ. Alpha-L-iduronidase in normal and mucopolysaccharidosis-type-I human skin fibroblasts. Biochem J 1991; 274 (Pt 1): 263-268
    CrossrefPubMedGoogle Scholar
  • 5 Kircher SG, Bajbouj M, Miebach E, Beck M. . Mucopolysaccharidoses - A Guide for Physicians and Parents. Bremen: International Medical Publishers; 2007
  • 6 Pérez-López J, Morales-Conejo M, López-Rodríguez M, Hermida-Ameijeiras Á, Moltó-Abad M. Efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age. A systematic review and meta-analysis. Mol Genet Metab 2017; 121 (02) 138-149
    CrossrefPubMedGoogle Scholar
  • 7 Aldenhoven M, Boelens JJ, de Koning TJ. The clinical outcome of Hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant 2008; 14 (05) 485-498
    CrossrefPubMedGoogle Scholar
  • 8 Parini R, Deodato F, Di Rocco M. , et al. Open issues in mucopolysaccharidosis type I-Hurler syndrome. Orphanet J Rare Dis 2017; 12 (01) 112
    CrossrefPubMedGoogle Scholar
  • 9 Valayannopoulos V, de Blic J, Mahlaoui N. , et al. Laronidase for cardiopulmonary disease in Hurler syndrome 12 years after bone marrow transplantation. Pediatrics 2010; 126 (05) e1242-e1247
    CrossrefPubMedGoogle Scholar
  • 10 Whiteman DA, Kimura A. Development of idursulfase therapy for mucopolysaccharidosis type II (Hunter syndrome): the past, the present and the future. Drug Des Devel Ther 2017; 11: 2467-2480
    CrossrefPubMedGoogle Scholar
  • 11 Garcia AR, DaCosta JM, Pan J, Muenzer J, Lamsa JC. Preclinical dose ranging studies for enzyme replacement therapy with idursulfase in a knock-out mouse model of MPS II. Mol Genet Metab 2007; 91 (02) 183-190
    CrossrefPubMedGoogle Scholar
  • 12 Muenzer J, Wraith JE, Beck M. , et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med 2006; 8 (08) 465-473
    PubMedGoogle Scholar
  • 13 Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab 2007; 90 (03) 329-337
    CrossrefPubMedGoogle Scholar
  • 14 Parini R, Rigoldi M, Tedesco L. , et al. Enzymatic replacement therapy for Hunter disease: up to 9 years experience with 17 patients. Mol Genet Metab Rep 2015; 3: 65-74
    CrossrefPubMedGoogle Scholar
  • 15 Gilkes JA, Heldermon CD. Mucopolysaccharidosis III (Sanfilippo syndrome)- disease presentation and experimental therapies. Pediatr Endocrinol Rev 2014; 12 (Suppl 1): 133-140
    PubMedGoogle Scholar
  • 16 Whitley C, Escolar ML, Vijay S. , et al. Initial, 24 Week Results of Heparan Sulfate Levels in Cerebrospinal Fluid (CSF) and Serum, Brain Structural MRI and Neurocognitive Evaluations in a Phase I/II, First-In-Human Clinical Trial of Intravenous SBC-103 in Mucopolysaccharidosis IIIB. Poster presented at 14th International Symposium on MPS and Related Diseases; Bonn, Germany; 14–17 July, 2016
    PubMed
  • 17 Shobhit S. Alexion Shelves Rare-Disease Drug SBC-103 (ALXN). Available at: https://www.investopedia.com 2017
    Google Scholar
  • 18 Ghosh A, Shapiro E, Rust S. , et al. Recommendations on clinical trial design for treatment of mucopolysaccharidosis type III. Orphanet J Rare Dis 2017; 12 (01) 117
    CrossrefPubMedGoogle Scholar
  • 19 Montaño AM, Tomatsu S, Gottesman GS, Smith M, Orii T. International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis 2007; 30 (02) 165-174
    CrossrefPubMedGoogle Scholar
  • 20 Dvorak-Ewell M, Wendt D, Hague C. , et al. Enzyme replacement in a human model of mucopolysaccharidosis IVA in vitro and its biodistribution in the cartilage of wild type mice. PLoS One 2010; 5 (08) e12194
    CrossrefPubMedGoogle Scholar
  • 21 Tomatsu S, Montaño AM, Gutierrez M. , et al. Characterization and pharmacokinetic study of recombinant human N-acetylgalactosamine-6-sulfate sulfatase. Mol Genet Metab 2007; 91 (01) 69-78
    CrossrefPubMedGoogle Scholar
  • 22 Puckett Y, Mulinder H, Montaño AM. Enzyme replacement therapy with elosulfase alfa for mucopolysaccharidosis IVA (Morquio A syndrome): milestones and challenges. Expert Opin Orphan Drugs 2017; 5 (09) 741-752
    PubMedGoogle Scholar
  • 23 Jones SA, Bialer M, Parini R. , et al. Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 years. Pediatr Res 2015; 78 (06) 717-722
    CrossrefPubMedGoogle Scholar
  • 24 Harmatz P, Shediac R. Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment. Front Biosci (Landmark Ed) 2017; 22: 385-406
    CrossrefPubMedGoogle Scholar
  • 25 Lin HY, Chuang CK, Wang CH. , et al. Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: a case series. Mol Genet Metab Rep 2016; 7: 63-69
    PubMedGoogle Scholar
  • 26 Harmatz P, Hendriksz CJ, Lampe C. , et al; MPS VI Study Group. The effect of galsulfase enzyme replacement therapy on the growth of patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Mol Genet Metab 2017; 122 (1–2): 107-112
    CrossrefPubMedGoogle Scholar
  • 27 Montaño AM, Lock-Hock N, Steiner RD. , et al. Clinical course of sly syndrome (mucopolysaccharidosis type VII). J Med Genet 2016; 53 (06) 403-418
    CrossrefPubMedGoogle Scholar
  • 28 Fox JE, Volpe L, Bullaro J, Kakkis ED, Sly WS. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient. Mol Genet Metab 2015; 114 (02) 203-208
    CrossrefPubMedGoogle Scholar
  • 29 Scarpa M, Orchard PJ, Schulz A. , et al. Treatment of brain disease in the mucopolysaccharidoses. Mol Genet Metab 2017; 122S: 25-34
    PubMedGoogle Scholar
  • 30 Eisengart JB, Rudser KD, Tolar J. , et al. Enzyme replacement is associated with better cognitive outcomes after transplant in Hurler syndrome. J Pediatr 2013; 162 (02) 375-80.e1
    CrossrefPubMedGoogle Scholar
  • 31 Macauley SL. Combination therapies for lysosomal storage diseases: acomplex answer to a simple problem. Pediatr Endocrinol Rev 2016; 13 (Suppl 1): 639-648
    PubMedGoogle Scholar
  • 32 Ou L, Herzog T, Koniar BL, Gunther R, Whitley CB. High-dose enzyme replacement therapy in murine Hurler syndrome. Mol Genet Metab 2014; 111 (02) 116-122
    CrossrefPubMedGoogle Scholar
  • 33 Cho SY, Lee J, Ko AR. , et al. Effect of systemic high dose enzyme replacement therapy on the improvement of CNS defects in a mouse model of mucopolysaccharidosis type II. Orphanet J Rare Dis 2015; 10: 141
    CrossrefPubMedGoogle Scholar
  • 34 Vogler C, Levy B, Grubb JH. , et al. Overcoming the blood-brain barrier with high-dose enzyme replacement therapy in murine mucopolysaccharidosis VII. Proc Natl Acad Sci U S A 2005; 102 (41) 14777-14782
    CrossrefPubMedGoogle Scholar
  • 35 Huynh HT, Grubb JH, Vogler C, Sly WS. Biochemical evidence for superior correction of neuronal storage by chemically modified enzyme in murine mucopolysaccharidosis VII. Proc Natl Acad Sci U S A 2012; 109 (42) 17022-17027
    CrossrefPubMedGoogle Scholar
  • 36 Kan SH, Troitskaya LA, Sinow CS. , et al. Insulin-like growth factor II peptide fusion enables uptake and lysosomal delivery of α-N-acetylglucosaminidase to mucopolysaccharidosis type IIIB fibroblasts. Biochem J 2014; 458 (02) 281-289
    CrossrefPubMedGoogle Scholar
  • 37 Boado RJ, Zhang Y, Zhang Y, Xia CF, Wang Y, Pardridge WM. Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood-brain barrier. Biotechnol Bioeng 2008; 99 (02) 475-484
    CrossrefPubMedGoogle Scholar
  • 38 Boado RJ, Hui EK, Lu JZ, Zhou QH, Pardridge WM. Reversal of lysosomal storage in brain of adult MPS-I mice with intravenous Trojan horse-iduronidase fusion protein. Mol Pharm 2011; 8 (04) 1342-1350
    CrossrefPubMedGoogle Scholar
  • 39 Nestrasil I, Shapiro E, Svatkova A. , et al. Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I. Am J Med Genet A 2017; 173 (03) 780-783
    CrossrefPubMedGoogle Scholar
  • 40 Jones SA, Breen C, Heap F. , et al. A phase 1/2 study of intrathecal heparan-N-sulfatase in patients with mucopolysaccharidosis IIIA. Mol Genet Metab 2016; 118 (03) 198-205
    CrossrefPubMedGoogle Scholar
  • 41 Wang RY, Rudser KD, Dengel DR. , et al. The carotid intima-media thickness and arterial stiffness of pediatric mucopolysaccharidosis patients are increased compared to both pediatric and adult controls. Int J Mol Sci 2017; 18 (03) 637
    CrossrefPubMedGoogle Scholar
  • 42 Lin HY, Chuang CK, Chen MR. , et al. Cardiac structure and function and effects of enzyme replacement therapy in patients with mucopolysaccharidoses I, II, IVA and VI. Mol Genet Metab 2016; 117 (04) 431-437
    CrossrefPubMedGoogle Scholar
  • 43 Brands MM, Frohn-Mulder IM, Hagemans ML. , et al. Mucopolysaccharidosis: cardiologic features and effects of enzyme-replacement therapy in 24 children with MPS I, II and VI. J Inherit Metab Dis 2013; 36 (02) 227-234
    CrossrefPubMedGoogle Scholar
  • 44 Sillence D, Waters K, Donaldson S, Shaw PJ, Ellaway C. Combined enzyme replacement therapy and hematopoietic stem cell transplantation in mucopolysaccharidosis type VI. JIMD Rep 2012; 2: 103-106
    PubMedGoogle Scholar
  • 45 Schulze-Frenking G, Jones SA, Roberts J, Beck M, Wraith JE. Effects of enzyme replacement therapy on growth in patients with mucopolysaccharidosis type II. J Inherit Metab Dis 2011; 34 (01) 203-208
    CrossrefPubMedGoogle Scholar
  • 46 Żuber Z, Różdżyńska-Świątkowska A, Jurecka A, Tylki-Szymańska A. The effect of recombinant human iduronate-2-sulfatase (Idursulfase) on growth in young patients with mucopolysaccharidosis type II. PLoS One 2014; 9 (01) e85074
    CrossrefPubMedGoogle Scholar
  • 47 Jones SA, Parini R, Harmatz P, Giugliani R, Fang J, Mendelsohn NJ. ; HOS Natural History Working Group on behalf of HOS Investigators. The effect of idursulfase on growth in patients with Hunter syndrome: data from the Hunter Outcome Survey (HOS). Mol Genet Metab 2013; 109 (01) 41-48
    CrossrefPubMedGoogle Scholar
  • 48 Scarpa M, Barone R, Fiumara A. , et al. Mucopolysaccharidosis VI: the Italian experience. Eur J Pediatr 2009; 168 (10) 1203-1206
    CrossrefPubMedGoogle Scholar
  • 49 Baldo G, Mayer FQ, Martinelli BZ. , et al. Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice. Mol Genet Metab 2013; 109 (01) 33-40
    CrossrefPubMedGoogle Scholar
  • 50 Do Cao J, Wiedemann A, Quinaux T. , et al. 30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: about one case. Mol Genet Metab Rep 2016; 9: 42-45
    PubMedGoogle Scholar
  • 51 Simonaro CM, D'Angelo M, Haskins ME, Schuchman EH. Joint and bone disease in mucopolysaccharidoses VI and VII: identification of new therapeutic targets and biomarkers using animal models. Pediatr Res 2005; 57 (5 Pt 1): 701-707
    CrossrefPubMedGoogle Scholar
  • 52 Tomatsu S, Alméciga-Díaz CJ, Barbosa H. , et al. Therapies of mucopolysaccharidosis IVA (Morquio A syndrome). Expert Opin Orphan Drugs 2013; 1 (10) 805-818
    PubMedGoogle Scholar
  • 53 Kishnani PS, Dickson PI, Muldowney L. , et al. Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction. Mol Genet Metab 2016; 117 (02) 66-83
    CrossrefPubMedGoogle Scholar
  • 54 Brands MM, Hoogeveen-Westerveld M, Kroos MA. , et al. Mucopolysaccharidosis type VI phenotypes-genotypes and antibody response to galsulfase. Orphanet J Rare Dis 2013; 8: 51
    CrossrefPubMedGoogle Scholar
  • 55 Ries M. Enzyme replacement therapy and beyond-in memoriam Roscoe O. Brady, M.D. (1923-2016). J Inherit Metab Dis 2017; 40 (03) 343-356
    CrossrefPubMedGoogle Scholar
  • 56 Furujo M, Kosuga M, Okuyama T. Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI: 10-Year follow up. Mol Genet Metab Rep 2017; 13: 69-75
    PubMedGoogle Scholar
  • 57 Sosa A, Kariuki B, Knutsen A. , et al. Induction of oral tolerance to N-acetylgalactosamine 6-sulfate sulfatase (GALNS) used for enzyme replacement therapy (ERT) in Morquio syndrome type A. Mol Genet Metab 2013; 108 (02) S86-S87
    PubMedGoogle Scholar
  • 58 Lee A, Sosa A, Montaño AM. Development of a less immunogenic protein for enzyme replacement therapy of Morquio syndrome type A disease. Mol Genet Metab 2015; 114 (02) S71
    PubMedGoogle Scholar