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Associations between neurologic dysfunction and lesions in canine fucosidosis

Citation

Fletcher, JL and Taylor, RM, Associations between neurologic dysfunction and lesions in canine fucosidosis, Genes Brain and Behavior, 15, (4) pp. 420-428. ISSN 1601-1848 (2016) [Refereed Article]

Copyright Statement

Copyright 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society

DOI: doi:10.1111/gbb.12282

Abstract

Canine fucosidosis in English Springer spaniels is the only animal model of the neurovisceral lysosomal storage disease fucosidosis available for preclinical therapeutic trials. For this reason, it is crucial to identify critical time points in disease progression, and if there are particular lesions associated with specific aspects of neurologic dysfunction. Historical records of 53 canine fucosidosis cases from 1979 to 2009 containing a neurologic dysfunction score assessing motor, behavioral and sensory dysfunction were interrogated by statistical analysis. Motor and behavioral dysfunction scores assessing gait deficits and apprehensive behavior first significantly increased at 12-17 months, and increased at each 6-month interval thereafter. Sensory dysfunction scores, assessing hearing loss, balance and vision deterioration, did not significantly increase until 18-23 months, and coincided with a rapid decline in neurologic function. Regression analysis incorporating published neuropathology data, measured by image analysis, identified neuroinflammation and apoptotic cell death as significant informative predictors of increasing neurologic dysfunction. These findings indicate that the level of neuropathology required to induce consistent and conspicuous clinical signs in canine fucosidosis is reached by approximately 12 months of age in the absence of other disease processes. Significant association between neuroinflammation and apoptotic cell death also suggests that specifically targeting these lesions combined with enzyme replacement in future studies may reduce disease burden in fucosidosis. Overall, examining this historical clinical data to identify associations between the extent of neuropathology and degree of clinical dysfunction provides a useful reference tool for monitoring disease and evaluating therapeutic trials conducted in canine fucosidosis.

Item Details

Item Type:Refereed Article
Keywords:lysosomal storage disease, animal model, demyelinating disease, CNS, clinical scoring system, fucosidosis, lysosomal storage disease, neuropathology
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Fletcher, JL (Dr Jessica Fletcher)
ID Code:147214
Year Published:2016
Web of Science® Times Cited:4
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-10-19
Last Modified:2021-11-16
Downloads:0

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