Open Access Features of Brain MRI in Dogs with Treated and Untreated Mucopolysaccharidosis Type I

 Download
(PDF 500.6kb)
 
Download Article:

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 age-matched 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.

Document Type: Research Article

Affiliations: 1: University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA USA 2: University of Minnesota School of Medicine, Minneapolis, MN USA 3: Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA USA 4: Iowa State University College of Agriculture and Life Sciences, Ames, IA USA 5: Duke University School of Medicine, Durham, NC USA, Emory University School of Medicine, Atlanta, GA USA 6: Duke University School of Medicine, Durham, NC USA 7: Children's Hospital Orange County, Orange, CA, USA 8: Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA USA. pdickson@labiomed.org

Publication date: April 1, 2013

More about this publication?
  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

    Attention Members: To access the full text of the articles, be sure you are logged in to the AALAS website.

    Attention: please note, due to a temporary technical problem, reference linking within the content is not available at this time
  • Editorial Board
  • Information for Authors
  • Submit a Paper
  • Subscribe to this Title
  • Membership Information
  • Information for Advertisers
  • For issues prior to 1998
  • Institutional Subscription Activation
  • ingentaconnect is not responsible for the content or availability of external websites

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more