Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

James M. Provenzale, Igor Nestrasil, Steven Chen, Shih hsin Kan, Steven Q. Le, Jacqueline K. Jens, Elizabeth M. Snella, Kristen N. Vondrak, Jennifer K. Yee, Charles H. Vite, David Elashoff, Lewei Duan, Raymond Y. Wang, N. Matthew Ellinwood, Miguel A. Guzman, Elsa G. Shapiro, Patricia I. Dickson

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-L-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-L-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalExperimental Neurology
Volume273
DOIs
StatePublished - Nov 1 2015

Keywords

  • Anisotropy
  • Brain
  • Diffusion tensor imaging
  • Enzyme replacement therapy
  • Hurler
  • Lysosomal storage disease
  • Neuroimaging
  • Scheie

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    Provenzale, J. M., Nestrasil, I., Chen, S., Kan, S. H., Le, S. Q., Jens, J. K., Snella, E. M., Vondrak, K. N., Yee, J. K., Vite, C. H., Elashoff, D., Duan, L., Wang, R. Y., Ellinwood, N. M., Guzman, M. A., Shapiro, E. G., & Dickson, P. I. (2015). Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I. Experimental Neurology, 273, 1-10. https://doi.org/10.1016/j.expneurol.2015.07.021