Abstract
Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Nonetheless, more often than not mouse models do not reproduce the pathophysiology of the human conditions they are designed to mimic. Naturally occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. In particular, numerous models have been discovered in dogs and have a fundamental role in bridging proof of concept studies in mice to human clinical trials. The present article is a review that highlights current canine models of human diseases, including Alzheimer's disease, degenerative myelopathy, neuronal ceroid lipofuscinosis, globoid cell leukodystrophy, Duchenne muscular dystrophy, mucopolysaccharidosis, and fucosidosis. The goal of the review is to discuss canine and human neurodegenerative pathophysiologic similarities, introduce the animal models, and shed light on the ability of canine models to facilitate current and future treatment trials.
Highlights
The utility of canine models of neurodegenerative diseases has increased over the last decade
Clinical trials of novel therapeutics for Alzheimer’s disease (AD) have not been tested in Canine Cognitive Dysfunction (CCD) dogs to our knowledge, and this is likely due to the complexities associated with conducting client owned animal clinical trials and/or a lack of a comprehensive natural history study of CCD
Even if the pathophysiology of degenerative myelopathy (DM) mimics only a fraction of Amyotrophic lateral sclerosis (ALS) cases, DM may remain a useful animal model for ALS insofar as it could afford us insights into the interplay between the unfolded protein response (UPR) of microglia and astrocytes and the spinal cord inflammation seen in the two diseases
Summary
Gray-Edwards HL (2020) Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases. Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. The present article is a review that highlights current canine models of human diseases, including Alzheimer’s disease, degenerative myelopathy, neuronal ceroid lipofuscinosis, globoid cell leukodystrophy, Duchenne muscular dystrophy, mucopolysaccharidosis, and fucosidosis. The goal of the review is to discuss canine and human neurodegenerative pathophysiologic similarities, introduce the animal models, and shed light on the ability of canine models to facilitate current and future treatment trials
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