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Long-term and high-dose trials of enzyme replacement therapy in the canine model of mucopolysaccharidosis I

Kakkis, Emil D.; McEntee, Michael F.; Schmidtchen, Artur LU ; Neufeld, Elizabeth F.; Ward, Daniel A.; Gompf, Rebecca E.; Kania, Stephen; Bedolla, Cathy; Chien, Shu-Lin and Shull, Robert M. (1996) In Biochemical and Molecular Medicine 58(2). p.156-167
Abstract
Enzyme replacement is a potential therapy for mucopolysaccharidosis I (MPS I), a lysosomal storage disorder caused by alpha-L-iduronidase deficiency. Previous work showed improvement in the tissues of MPS I dogs treated intravenously for 3 months with recombinant human alpha-L-iduronidase (25,000 units or approximately 0.1 mg/kg/week). We have now treated an MPS I-affected dog for 13 months to assess the clinical effects of enzyme replacement. The treated dog gained more weight, was more active, and had less joint stiffness than the untreated littermate. Biochemical and histologic studies demonstrated uptake of alpha-L-iduronidase and decreased lysosomal storage in the liver, kidney, spleen, lymph nodes, synovium, adrenals, and lungs. The... (More)
Enzyme replacement is a potential therapy for mucopolysaccharidosis I (MPS I), a lysosomal storage disorder caused by alpha-L-iduronidase deficiency. Previous work showed improvement in the tissues of MPS I dogs treated intravenously for 3 months with recombinant human alpha-L-iduronidase (25,000 units or approximately 0.1 mg/kg/week). We have now treated an MPS I-affected dog for 13 months to assess the clinical effects of enzyme replacement. The treated dog gained more weight, was more active, and had less joint stiffness than the untreated littermate. Biochemical and histologic studies demonstrated uptake of alpha-L-iduronidase and decreased lysosomal storage in the liver, kidney, spleen, lymph nodes, synovium, adrenals, and lungs. The brain had detectable enzyme activity and decreased glycosaminoglycan storage although histologic improvement was not evident. Cartilage and heart valve did not show any detectable improvement. A fivefold higher dose (approximately 0.5 mg/kg) administered five times over 10 days to two other dogs resulted in higher tissue enzyme activity and similarly decreased glycosaminoglycan storage and excretion. Antibodies to human alpha-L-iduronidase were induced in all treated dogs and may be associated with immune complex deposition and proteinuria. Recombinant canine alpha-L-iduronidase also induced antibody formation to a similar degree. The results support the conclusion that enzyme replacement is a promising therapy for MPS I though immunologic complications may occur. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Molecular Medicine
volume
58
issue
2
pages
156 - 167
publisher
Academic Press
external identifiers
  • pmid:8812735
  • scopus:0030221033
ISSN
1077-3150
DOI
10.1006/bmme.1996.0044
language
English
LU publication?
no
id
61900633-f261-4536-854c-987c4db79430 (old id 1110807)
date added to LUP
2008-07-24 10:51:40
date last changed
2017-07-23 04:31:39
@article{61900633-f261-4536-854c-987c4db79430,
  abstract     = {Enzyme replacement is a potential therapy for mucopolysaccharidosis I (MPS I), a lysosomal storage disorder caused by alpha-L-iduronidase deficiency. Previous work showed improvement in the tissues of MPS I dogs treated intravenously for 3 months with recombinant human alpha-L-iduronidase (25,000 units or approximately 0.1 mg/kg/week). We have now treated an MPS I-affected dog for 13 months to assess the clinical effects of enzyme replacement. The treated dog gained more weight, was more active, and had less joint stiffness than the untreated littermate. Biochemical and histologic studies demonstrated uptake of alpha-L-iduronidase and decreased lysosomal storage in the liver, kidney, spleen, lymph nodes, synovium, adrenals, and lungs. The brain had detectable enzyme activity and decreased glycosaminoglycan storage although histologic improvement was not evident. Cartilage and heart valve did not show any detectable improvement. A fivefold higher dose (approximately 0.5 mg/kg) administered five times over 10 days to two other dogs resulted in higher tissue enzyme activity and similarly decreased glycosaminoglycan storage and excretion. Antibodies to human alpha-L-iduronidase were induced in all treated dogs and may be associated with immune complex deposition and proteinuria. Recombinant canine alpha-L-iduronidase also induced antibody formation to a similar degree. The results support the conclusion that enzyme replacement is a promising therapy for MPS I though immunologic complications may occur.},
  author       = {Kakkis, Emil D. and McEntee, Michael F. and Schmidtchen, Artur and Neufeld, Elizabeth F. and Ward, Daniel A. and Gompf, Rebecca E. and Kania, Stephen and Bedolla, Cathy and Chien, Shu-Lin and Shull, Robert M.},
  issn         = {1077-3150},
  language     = {eng},
  number       = {2},
  pages        = {156--167},
  publisher    = {Academic Press},
  series       = {Biochemical and Molecular Medicine},
  title        = {Long-term and high-dose trials of enzyme replacement therapy in the canine model of mucopolysaccharidosis I},
  url          = {http://dx.doi.org/10.1006/bmme.1996.0044},
  volume       = {58},
  year         = {1996},
}