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Glycosaminoglycan storage in neuroanatomical regions of mucopolysaccharidosis I dogs following intrathecal recombinant human iduronidase
Author(s) -
CHEN AGNES,
VOGLER CAROLE,
MCENTEE MICHAEL,
HANSON STEPHEN,
MATTHEW ELLINWOOD N.,
JENS JACKIE,
SNELLA ELIZABETH,
PASSAGE MERRY,
LE STEVEN,
GUERRA CATALINA,
DICKSON PATRICIA
Publication year - 2011
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2011.02760.x
Subject(s) - thalamus , mucopolysaccharidosis i , cerebellum , basal ganglia , frontal lobe , hippocampus , mucopolysaccharidosis type i , brainstem , cerebral cortex , anatomy , pathology , medicine , biology , central nervous system , endocrinology , neuroscience , enzyme replacement therapy , disease
Chen A, Vogler C, McEntee M, Hanson S, Ellinwood MN, Jens J, Snella E, Passage M, Le S, Guerra C, Dickson P. Glycosaminoglycan storage in neuroanatomical regions of mucopolysaccharidosis I dogs following intrathecal recombinant human iduronidase. APMIS 2011; 119: 513–21. Intrathecal (IT) recombinant human α‐ l ‐iduronidase (rhIDU) has been shown to reduce mean brain glycosaminoglycans (GAGs) to normal levels in mucopolysaccharidosis I (MPS I) dogs. In this study, we examined storage in neuroanatomical regions of the MPS I dog brain, including frontal lobe, cerebellum, basal ganglia, thalamus, hippocampal formation, and brainstem, to determine the response of these functional regions to treatment with IT rhIDU. GAG storage in untreated MPS I dogs was significantly different from normal dogs in all examined sections. GAG levels in normal dogs varied by region: frontal lobe (mean: 2.36 ± 0.54 μg/mg protein), cerebellum (2.67 ± 0.33), basal ganglia and thalamus (3.51 ± 0.60), hippocampus (3.30 ± 0.40), and brainstem (3.73 ± 1.10). Following IT treatment, there was a reduction in GAG storage in each region in all treatment groups, except for the brainstem. Percent reduction in GAG levels from untreated to treated MPS I dogs in the deeper regions of the brain was 30% for basal ganglia and thalamus and 30% for hippocampus, and storage reduction was greater in superficial regions, with 61% reduction in the frontal lobe and 54% in the cerebellum compared with untreated MPS I dogs. Secondary lipid storage in neurons was also reduced in frontal lobe, but not in the other brain regions examined. Response to therapy appeared to be greater in more superficial regions of the brain, particularly in the frontal lobe cortex.