Bone marrow transplantation for feline mucopolysaccharidosis I

N. Matthew Ellinwood, Marie Anne Colle, Margaret A. Weil, Margret L. Casal, Charles H. Vite, Staci Wiemelt, Christopher W. Hasson, Thomas M. O'Malley, Xingxuan He, Ulana Prociuk, Lucie Verot, John R. Melniczek, Anne Lannon, Gustavo D. Aguirre, Van W. Knox, Sydney M. Evans, Marie T. Vanier, Edward H. Schuchman, Steven U. Walkley, Mark E. Haskins

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Severe mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3 × 107-1.1 × 109 nucleated bone marrow cells per kilogram) were monitored for 13-37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to normal levels in liver, spleen, kidney, heart muscle, lung, and thyroid. Aorta GAG content was between normal and affected levels. Treated cats had a significant decrease in the brain GAG levels relative to untreated MPS I cats and a paradoxical decrease relative to normal cats. The α-l-iduronidase (IDUA) activity in the livers and spleens of transplanted MPS I cats approached heterozygote levels. In kidney cortex, aorta, heart muscle, and cerebrum, there were decreases in GAG without significant increases in detectable IDUA activity. Treated animals had improved mobility and decreased radiographic signs of disease. However, significant pathology remained, especially in the cervical spine. Corneal clouding appeared improved in some animals. Immunohistochemical and biochemical analysis documented decreased central nervous system ganglioside storage. This large animal MPS I study will serve as a benchmark of future therapies designed to improve on BMT.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalMolecular Genetics and Metabolism
Volume91
Issue number3
DOIs
StatePublished - Jul 2007

Fingerprint

Mucopolysaccharidosis I
Felidae
Bone Marrow Transplantation
Bone
Glycosaminoglycans
Animals
Iduronidase
Cats
Liver
Muscle
Aorta
Myocardium
Spleen
Gangliosides
Benchmarking
Kidney Cortex
Neurology
Pathology
Cerebrum
Heterozygote

Keywords

  • Bone marrow transplantation
  • Disease models, animal
  • Glycosaminoglycans
  • Iduronidase
  • Lysosomal storage diseases
  • Mucopolysaccharidosis I

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Ellinwood, N. M., Colle, M. A., Weil, M. A., Casal, M. L., Vite, C. H., Wiemelt, S., ... Haskins, M. E. (2007). Bone marrow transplantation for feline mucopolysaccharidosis I. Molecular Genetics and Metabolism, 91(3), 239-250. https://doi.org/10.1016/j.ymgme.2007.03.001

Bone marrow transplantation for feline mucopolysaccharidosis I. / Ellinwood, N. Matthew; Colle, Marie Anne; Weil, Margaret A.; Casal, Margret L.; Vite, Charles H.; Wiemelt, Staci; Hasson, Christopher W.; O'Malley, Thomas M.; He, Xingxuan; Prociuk, Ulana; Verot, Lucie; Melniczek, John R.; Lannon, Anne; Aguirre, Gustavo D.; Knox, Van W.; Evans, Sydney M.; Vanier, Marie T.; Schuchman, Edward H.; Walkley, Steven U.; Haskins, Mark E.

In: Molecular Genetics and Metabolism, Vol. 91, No. 3, 07.2007, p. 239-250.

Research output: Contribution to journalArticle

Ellinwood, NM, Colle, MA, Weil, MA, Casal, ML, Vite, CH, Wiemelt, S, Hasson, CW, O'Malley, TM, He, X, Prociuk, U, Verot, L, Melniczek, JR, Lannon, A, Aguirre, GD, Knox, VW, Evans, SM, Vanier, MT, Schuchman, EH, Walkley, SU & Haskins, ME 2007, 'Bone marrow transplantation for feline mucopolysaccharidosis I', Molecular Genetics and Metabolism, vol. 91, no. 3, pp. 239-250. https://doi.org/10.1016/j.ymgme.2007.03.001
Ellinwood NM, Colle MA, Weil MA, Casal ML, Vite CH, Wiemelt S et al. Bone marrow transplantation for feline mucopolysaccharidosis I. Molecular Genetics and Metabolism. 2007 Jul;91(3):239-250. https://doi.org/10.1016/j.ymgme.2007.03.001
Ellinwood, N. Matthew ; Colle, Marie Anne ; Weil, Margaret A. ; Casal, Margret L. ; Vite, Charles H. ; Wiemelt, Staci ; Hasson, Christopher W. ; O'Malley, Thomas M. ; He, Xingxuan ; Prociuk, Ulana ; Verot, Lucie ; Melniczek, John R. ; Lannon, Anne ; Aguirre, Gustavo D. ; Knox, Van W. ; Evans, Sydney M. ; Vanier, Marie T. ; Schuchman, Edward H. ; Walkley, Steven U. ; Haskins, Mark E. / Bone marrow transplantation for feline mucopolysaccharidosis I. In: Molecular Genetics and Metabolism. 2007 ; Vol. 91, No. 3. pp. 239-250.
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