Features of brain MRI in dogs with treated and untreated mucopolysaccharidosis type i

Charles H. Vite, Igor Nestrasil, Anton Mlikotic, Jackie K. Jens, Elizabeth M. Snella, William Gross, Elsa G Shapiro, Victor Kovac, James M. Provenzale, Steven Chen, Steven Q. Le, Shih Hsin Kan, Shida Banakar, Raymond Y. Wang, Mark E. Haskins, N. Matthew Ellinwood, Patricia I. Dickson

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The mucopolysaccharidosis type I (MPS I) dog model has been important in the development of therapies for human patients. We treated dogs with enzyme replacement therapy (ERT) by various approaches. Dogs assessed included untreated MPS I dogs, heterozygous carrier dogs, and MPS I dogs treated with intravenous ERT as adults (beginning at age 13 to 16 mo), intrathecal and intravenous ERT as adults (beginning at age 13 to 16 mo), or intrathecal ERT as juveniles (beginning at age 4 mo). We then characterized the neuroimaging findings of 32 of these dogs (age, 12 to 30 mo). Whole and midsagittal volumes of the corpus callosum, measured from brain MRI, were significantly smaller in affected dogs compared with unaffected heterozygotes. Corpus callosum volumes in dogs that were treated with intrathecal ERT from 4 mo until 21 mo of age were indistinguishable from those of agematched carrier controls. Dogs with MPS I showed cerebral ventricular enlargement and cortical atrophy as early as 12 mo of age. Ventricular enlargement was greater in untreated MPS I dogs than in age-matched dogs treated with intrathecal ERT as juveniles or adults. However, treated dogs still showed some ventricular enlargement or cortical atrophy (or both). Understanding the progression of neuroimaging findings in dogs with MPS I and their response to brain-directed therapy may improve preclinical studies for new human-directed therapies. In particular, corpus callosum volumes may be useful quantitative neuroimaging markers for MPS-related brain disease and its response to therapy.

Original languageEnglish (US)
Pages (from-to)163-173
Number of pages11
JournalComparative medicine
Volume63
Issue number2
StatePublished - Apr 2013

Fingerprint

Dive into the research topics of 'Features of brain MRI in dogs with treated and untreated mucopolysaccharidosis type i'. Together they form a unique fingerprint.

Cite this