Abstract

Canine degenerative myelopathy (DM), recognized as a spontaneous model of amyotrophic lateral sclerosis, is known as a late-onset progressive degenerative disease of the spinal cord. Because of the progressive nature of DM, many dogs are elected to be euthanized, resulting in limited information on the end-stage clinical presentation. We investigated the long-term clinical course from diagnosis to natural death to further deepen our understanding of the entire clinical picture of this disease. Because curcumin was administered in some cases, the therapeutic effect of curcumin on DM was also examined. Forty dogs included in this study were client-owned Pembroke Welsh Corgis with a definitive diagnosis of DM by necropsy and histopathology. Dogs were excluded from this study if they died from another disease or were elected to be euthanized. Information on the long-term clinical symptoms of DM was investigated based on a questionnaire, which was collected from the dog owners. Urinary incontinence and respiratory disorder were observed in most dogs, as was respiratory impairment-correlated death. In contrast, signs consistent with brainstem dysfunction were noticed at the terminal stage in a small portion of dogs. Although further studies with more cases are needed, the results of this study suggest that administration of curcumin is effective in slowing the progression of DM.

Highlights

  • Canine degenerative myelopathy (DM) is a slowly progressive fatal neurodegenerative disorder that affects the spinal cord [1]

  • All dogs were homozygous for the c.118G>A mutation in the superoxide dismutase 1 (SOD1) gene

  • This study indicated that urinary and fecal incontinence was present in a high percentage of dogs with DM, which was similar to what was noted in patients with amyotrophic lateral sclerosis (ALS) [19]

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Summary

Introduction

Canine degenerative myelopathy (DM) is a slowly progressive fatal neurodegenerative disorder that affects the spinal cord [1]. DM-affected dogs are homozygous for the A allele of a SOD1 missense mutation, SOD1: c.118G>A and c.52A>T, which predicts a p.E40K and T18S amino acid substitution [2,3]. DM has been recently considered a spontaneous model of familial amyotrophic lateral sclerosis (ALS) [4]. ALS is a neurodegenerative disorder characterized by progressive muscle weakness, and 20% of patients with familial ALS have SOD1 gene mutations similar to those found in DM-affected dogs [5,6,7]. In DM and ALS, the exact molecular mechanisms underlying mutant SOD1-mediated neurodegeneration are unclear

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