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Laronidase Treatment of Mucopolysaccharidosis I

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Abstract

The lysosomal storage disorder (LSD) mucopolysaccharidosis type I (MPS I, McKusick 25280, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome) is caused by a deficiency in the lysosomal enzyme, α-L-iduronidase (EC 3.2.1.76). MPS I patients can present within a diverse clinical spectrum, ranging from classical Hurler syndrome to attenuated Scheie syndrome. Laronidase (Aldurazyme®) enzyme replacement therapy has been developed as a treatment strategy for MPS I patients and has been approved for clinical practice. Here we review the pre-clinical studies and clinical trials that have been used to demonstrate that intravenous laronidase therapy is well tolerated and effective for treating MPS I patients who do not have neuronal pathology. Current challenges for a viable treatment strategy for all MPS I patients include development of an early screening protocol that identifies patients before the onset of irreversible pathology, methods to predict disease severity, appropriate treatment for neuropathology, and an effective patient monitoring regimen.

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Notes

  1. International Union of Biochemistry and Molecular Biology [IUBMB] nomenclature; (see URL: http://www.chem.qmul.ac.uk/iubmb/enzyme/)

  2. The use of trade names is for product identification purposes only and does not imply endorsement

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Acknowledgments

This work was supported by the National Health and Medical Research Council of Australia, by Fellowship and Program grant funding. D.A. Brooks and J.J. Hopwood have developed intellectual property relating to α-L-iduronidase and mucopolysaccharidosis I. J.J. Hopwood is a consultant for Transkaryotic Therapies. J.J. Hopwood and P.J. Meikle currently receive research funds from Genzyme Corporation.

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Authors and Affiliations

  1. Willink Biochemical Genetics Unit, Royal Manchester Children’s Hospital, Manchester, UK

    Ed J. Wraith

  2. Lysosomal Disease Research Unit, Department of Genetic Medicine, Women’s and Children’s Hospital, 72 King William Road, Adelaide, South Australia, 5006, Australia

    John J. Hopwood, Maria Fuller, Peter J. Meikle &  Doug A. Brooks

  3. Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia

    John J. Hopwood, Maria Fuller, Peter J. Meikle &  Doug A. Brooks

Authors
  1. Ed J. Wraith
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  2. John J. Hopwood
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  3. Maria Fuller
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  4. Peter J. Meikle
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  5. Doug A. Brooks
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Correspondence to Doug A. Brooks.

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Wraith, E.J., Hopwood, J.J., Fuller, M. et al. Laronidase Treatment of Mucopolysaccharidosis I. BioDrugs 19, 1–7 (2005). https://doi.org/10.2165/00063030-200519010-00001

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