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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Provenzale, JM; Nestrasil, I; Chen, S; Kan, S-H; Le, SQ; Jens, JK; Snella, EM; Vondrak, KN; Yee, JK; Vite, CH; Elashoff, D; Duan, L; Wang, RY; Ellinwood, NM; Guzman, MA; Shapiro, EG; Dickson, PI

Published Date

  • November 2015

Published In

Volume / Issue

  • 273 /

Start / End Page

  • 1 - 10

PubMed ID

  • 26222335

Pubmed Central ID

  • PMC4644459

Electronic International Standard Serial Number (EISSN)

  • 1090-2430

Digital Object Identifier (DOI)

  • 10.1016/j.expneurol.2015.07.021


  • eng

Conference Location

  • United States