Genetically modified rodent models of Huntington's disease (HD) have been especially valuable to our understanding of HD pathology and the mechanisms by which the mutant HTT gene alters physiology. However, due to inherent differences in genetics, neuroanatomy, neurocircuitry and neurophysiology, animal models do not always faithfully or fully recapitulate human disease features or adequately predict a clinical response to treatment. Therefore, conducting translational studies of candidate HD therapeutics only in a single species (i.e. mouse disease models) may not be sufficient. Large animal models of HD have been shown to be valuable to the HD research community and the expectation is that the need for translational studies that span rodent and large animal models will grow. Here, we review the large animal models of HD that have been created to date, with specific commentary on differences between the models, the strengths and disadvantages of each, and how we can advance useful models to study disease pathophysiology, biomarker development and evaluation of promising therapeutics.

CHDI Management CHDI Foundation Princeton NJ USA

Diplomate MedVet American College of Veterinary Internal Medicine Neurology Columbus OH USA

Horae Gene Therapy Center and RNA Therapeutics Institute at The University of Massachusetts Medical School Worcester MA USA

Institute of Animal Physiology and Genetics Libechov Czech Republic

Oregon National Primate Research Center at The Oregon Health and Science University Portland OR USA

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Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington's Disease and Human Blood Plasma