title: alpha-L-iduronidase therapy for mucopolysaccharidosis type I.
abstract: More than 500 patients with mucopolysaccharidosis type IH (MPS IH; Hurler syndrome) have been treated with hematopoietic cell transplantation (HCT) throughout the world since the introduction of transplantation as therapy almost 30 years ago. More recently, the availability of recombinant alpha-L-iduronidase (IDUA) has resulted in the widespread treatment of less severe forms of MPS I with enzyme replacement therapy (ERT). In addition, over 50 MPS IH patients have been treated with a combination of ERT and HCT. The rationale for both ERT and HCT stems from the pivotal experiments performed 4 decades ago that showed alpha-L-iduronidase supplied in the environment can correct the accumulation of substrate in MPS I cells. Our purpose is to address the multiple applications associated with the therapeutic delivery of IDUA: intermittent delivery of recombinant protein (ERT), continuous administration through cellular therapy (HCT), the use of other stem cells or, potentially, correction of the enzyme defect itself through gene therapy approaches. Even though gene therapy and non-hematopoietic stem cell approaches, have yet to be tested in a clinical setting, it is possible that all these approaches will in the near future be a part of a paradigm shift from unimodal to multimodal therapy for MPS I.
authors.affiliation: Division of Hematology, Oncology, Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
references.citation: Hum Mutat. 1995;6(4):288-302
references.pmid: 8680403
references.citation: Mol Genet Metab. 2000 Apr;69(4):277-85
references.pmid: 10870845
references.citation: Radiology. 1985 Mar;154(3):665-6
references.pmid: 3918332
references.citation: J Inherit Metab Dis. 2007 Oct;30(5):820
references.pmid: 17768668
references.citation: Blood. 1996 Jul 1;88(1):377-9
references.pmid: 8704199
references.citation: Biochem J. 1994 Nov 15;304 ( Pt 1):43-9
references.pmid: 7998955
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):829-34
references.pmid: 14715900
references.citation: J Biol Chem. 1980 May 25;255(10):4946-50
references.pmid: 6989822
references.citation: Blood. 2003 Mar 15;101(6):2099-114
references.pmid: 12511419
references.citation: Bone Marrow Transplant. 2002 Aug;30(4):215-22
references.pmid: 12203137
references.citation: Mol Genet Metab. 2002 Sep-Oct;77(1-2):127-35
references.pmid: 12359140
references.citation: J Pediatr. 2004 May;144(5):581-8
references.pmid: 15126990
references.citation: Proc Natl Acad Sci U S A. 1968 Jun;60(2):699-706
references.pmid: 4236091
references.citation: Bone Marrow Transplant. 2008 Mar;41(6):531-5
references.pmid: 18037941
references.citation: Blood. 1998 Apr 1;91(7):2601-8
references.pmid: 9516162
references.citation: Science. 1968 Nov 1;162(3853):570-2
references.pmid: 4236721
references.citation: Clin Pharmacol Ther. 2007 Sep;82(3):241-3
references.pmid: 17700588
references.citation: J Am Soc Nephrol. 2006 Aug;17(8):2202-12
references.pmid: 16790513
references.citation: Mol Ther. 2007 Aug;15(8):1423-31
references.pmid: 17519893
references.citation: Bone Marrow Transplant. 2007 Aug;40(3):225-33
references.pmid: 17529997
references.citation: Biochem Mol Med. 1996 Aug;58(2):156-67
references.pmid: 8812735
references.citation: Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12937-41
references.pmid: 7809150
references.citation: Cell Transplant. 1995 Jul-Aug;4(4):385-92
references.pmid: 7582569
references.citation: Exp Hematol. 2006 Oct;34(10):1413-9
references.pmid: 16982334
references.citation: J Biol Chem. 1980 Oct 25;255(20):9608-15
references.pmid: 6253448
references.citation: Am J Hum Genet. 1993 Nov;53(5):973-86
references.pmid: 8213840
references.citation: Bone Marrow Transplant. 2006 Jul;38(1):17-21
references.pmid: 16715104
references.citation: Mol Genet Metab. 2007 May;91(1):37-47
references.pmid: 17336562
references.citation: Pediatrics. 2007 Jul;120(1):e37-46
references.pmid: 17606547
references.citation: J Hum Genet. 2008;53(5):467-474
references.pmid: 18340403
references.citation: Am J Med Genet. 1985 Mar;20(3):471-81
references.pmid: 3922223
references.citation: Blood. 1997 Aug 1;90(3):986-93
references.pmid: 9242527
references.citation: Mol Ther. 2005 Jan;11(1):35-47
references.pmid: 15585404
references.citation: Pediatr Transplant. 1998 Nov;2(4):250-3
references.pmid: 10084724
references.citation: Pediatr Radiol. 1987;17(5):409-14
references.pmid: 3114705
references.citation: Mol Genet Metab. 2007 May;91(1):61-8
references.pmid: 17321776
references.citation: J Pediatr Orthop. 1996 Nov-Dec;16(6):731-3
references.pmid: 8906643
references.citation: Pediatr Res. 2006 Jan;59(1):27-32
references.pmid: 16326988
references.citation: Protein Expr Purif. 1994 Jun;5(3):225-32
references.pmid: 7950365
references.citation: Semin Hematol. 2004 Oct;41(4):303-18
references.pmid: 15508116
references.citation: Bone Marrow Transplant. 2007 Mar;39(6):331-4
references.pmid: 17277793
references.citation: Biol Blood Marrow Transplant. 2005 May;11(5):321-34
references.pmid: 15846285
references.citation: J Inherit Metab Dis. 1995;18(4):413-29
references.pmid: 7494400
references.citation: Bone Marrow Transplant. 2008 Jun;41(12):1005-11
references.pmid: 18278070
references.citation: Eur J Pediatr. 1998 Jul;157(7):534-8
references.pmid: 9686810
references.citation: N Engl J Med. 2001 Jan 18;344(3):182-8
references.pmid: 11172140
references.citation: Mol Ther. 2007 May;15(5):889-902
references.pmid: 17311010
references.citation: Bone Marrow Transplant. 2003 Jun;31(12):1105-17
references.pmid: 12796790
references.citation: Surg Neurol. 1982 Jun;17(6):404-10
references.pmid: 6810485
references.citation: Mol Genet Metab. 2007 Feb;90(2):181-92
references.pmid: 16979922
references.citation: Bone Marrow Transplant. 2003 Jul;32(2):213-5
references.pmid: 12838287
references.citation: Lancet. 2004 May 1;363(9419):1439-41
references.pmid: 15121408
references.citation: Clin Genet. 1998 May;53(5):349-61
references.pmid: 9660052
references.citation: J Gene Med. 2004 May;6(5):481-506
references.pmid: 15133760
references.citation: NeuroRx. 2005 Jan;2(1):1-2
references.pmid: 15717052
references.citation: Blood. 2007 Apr 15;109(8):3147-51
references.pmid: 17170129
references.citation: N Engl J Med. 2004 May 6;350(19):1960-9
references.pmid: 15128896
references.citation: J Pediatr Orthop. 1999 Mar-Apr;19(2):270-4
references.pmid: 10088702
references.citation: Bone Marrow Transplant. 2008 Feb;41(4):349-53
references.pmid: 18026148
references.citation: Gene Ther. 2006 Jun;13(11):917-25
references.pmid: 16482204
references.citation: J Pediatr. 1998 Jul;133(1):7-9
references.pmid: 9672503
references.citation: Mol Genet Metab. 2007 Feb;90(2):171-80
references.pmid: 17011223
references.citation: Expert Opin Biol Ther. 2007 Sep;7(9):1333-45
references.pmid: 17727324
references.citation: J Thromb Haemost. 2008 May;6(5):893-5
references.pmid: 18315551
references.citation: Mol Genet Metab. 2001 Mar;72(3):199-208
references.pmid: 11243725
references.citation: Haematologica. 2005 Apr;90(4):438
references.pmid: 15820935
references.citation: NeuroRx. 2005 Jan;2(1):3-14
references.pmid: 15717053
references.citation: Mol Ther. 2004 Jun;9(6):866-75
references.pmid: 15194053
references.citation: Mol Genet Metab. 2005 May;85(1):28-37
references.pmid: 15862278
references.citation: Pediatr Cardiol. 1992 Apr;13(2):107-9
references.pmid: 1614914
references.citation: J Pediatr Orthop. 2008 Mar;28(2):163-8
references.pmid: 18388709
references.citation: Blood. 2005 Feb 15;105(4):1815-22
references.pmid: 15494428
references.citation: N Engl J Med. 2003 Jan 16;348(3):255-6
references.pmid: 12529469
references.citation: J Biol Chem. 1984 Mar 10;259(5):3132-40
references.pmid: 6421818
references.citation: N Engl J Med. 2004 Jun 10;350(24):2526-7; author reply 2526-7
references.pmid: 15190153
references.citation: Mol Cell Biol. 2003 Dec;23(24):9003-13
references.pmid: 14645513
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1902-7
references.pmid: 12576554
references.citation: Am J Cardiol. 1976 Oct;38(4):487-501
references.pmid: 823811
references.citation: Arch Dis Child. 1997 Feb;76(2):92-9
references.pmid: 9068295
references.citation: Mol Biotechnol. 2005 May;30(1):57-70
references.pmid: 15805577
references.citation: Genet Med. 2005 Feb;7(2):143-6
references.pmid: 15714083
references.citation: FASEB J. 2006 Jan;20(1):9-22
references.pmid: 16394262
references.citation: Bone Marrow Transplant. 2002 Mar;29(6):491-6
references.pmid: 11960268
references.citation: J Pediatr. 2007 Oct;151(4):340-6
references.pmid: 17889065
references.citation: JAMA. 1999 Jan 20;281(3):249-54
references.pmid: 9918480
references.citation: Hum Gene Ther. 2005 Jan;16(1):81-90
references.pmid: 15703491
references.citation: Hum Mol Genet. 1997 Apr;6(4):503-11
references.pmid: 9097952
references.citation: Annu Rev Biochem. 1991;60:257-80
references.pmid: 1883197
references.citation: Proc Natl Acad Sci U S A. 1972 Aug;69(8):2048-51
references.pmid: 4262258
references.citation: Mol Ther. 2008 Aug;16(8):1459-66
references.pmid: 18523448
references.citation: Mol Genet Metab. 2004 Sep-Oct;83(1-2):163-74
references.pmid: 15464431
references.citation: J Pediatr. 2008 May;152(5):723-7
references.pmid: 18410781
references.citation: Blood. 1996 Jun 1;87(11):4894-902
references.pmid: 8639864
references.citation: J Pediatr Orthop. 2004 Jan-Feb;24(1):97-101
references.pmid: 14676543
references.citation: Lancet. 1981 Oct 3;2(8249):709-12
references.pmid: 6116856
references.citation: PLoS Genet. 2006 Sep 29;2(9):e133
references.pmid: 17009872
references.citation: Hum Gene Ther. 1999 Jun 10;10(9):1521-32
references.pmid: 10395377
references.citation: Curr Opin Neurol. 1999 Apr;12(2):167-76
references.pmid: 10226749
references.citation: Science. 2003 Oct 17;302(5644):415-9
references.pmid: 14564000
references.citation: J Bone Joint Surg Br. 1994 Nov;76(6):975-81
references.pmid: 7983131
references.citation: Dev Med Child Neurol. 1973 Apr;15(2):194-9
references.pmid: 4266829
references.citation: Hum Mutat. 1992;1(4):333-9
references.pmid: 1301941
references.citation: Lancet. 2003 May 10;361(9369):1608-13
references.pmid: 12747881
references.citation: Mol Ther. 2005 May;11(5):776-89
references.pmid: 15851016
references.citation: Mol Genet Metab. 2003 Aug;79(4):233-44
references.pmid: 12948739
references.citation: Am J Cardiol. 2003 Oct 1;92(7):882-6
references.pmid: 14516901
references.citation: J Med Genet. 1997 Nov;34(11):939-41
references.pmid: 9391892
references.citation: Clin Genet. 1999 Jul;56(1):66-70
references.pmid: 10466419
references.citation: J Inherit Metab Dis. 2001 Apr;24(2):245-50
references.pmid: 11405343