title: Features of brain MRI in dogs with treated and untreated mucopolysaccharidosis type I.
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.
authors.affiliation: University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Vite
authors.forename: Igor
authors.initials: I
authors.lastname: Nestrasil
authors.forename: Anton
authors.initials: A
authors.lastname: Mlikotic
authors.forename: Jackie K
authors.initials: JK
authors.lastname: Jens
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Snella
authors.forename: William
authors.initials: W
authors.lastname: Gross
authors.forename: Elsa G
authors.initials: EG
authors.lastname: Shapiro
authors.forename: Victor
authors.initials: V
authors.lastname: Kovac
authors.forename: James M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: Steven
authors.initials: S
authors.lastname: Chen
authors.forename: Steven Q
authors.initials: SQ
authors.lastname: Le
authors.forename: Shih-hsin
authors.initials: SH
authors.lastname: Kan
authors.forename: Shida
authors.initials: S
authors.lastname: Banakar
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Wang
authors.forename: Mark E
authors.initials: ME
authors.lastname: Haskins
authors.forename: N Matthew
authors.initials: NM
authors.lastname: Ellinwood
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Dickson
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D056947:Enzyme Replacement Therapy / Q000379:methods*; D005260:Female; D007068:Iduronidase / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008059:Mucopolysaccharidosis I / Q000188:drug therapy* / Q000473:pathology; D059906:Neuroimaging; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D007068:Iduronidase