Modelling Neurological Diseases in Large Animals: Criteria for Model Selection and Clinical Assessment

Samantha L. Eaton, Fraser Murdoch, Nina M. Rzechorzek, Gerard Thompson, Claudia Hartley, Benjamin Thomas Blacklock, Chris Proudfoot, Simon G. Lillico, Peter Tennant, Adrian Ritchie, James Nixon, Paul M. Brennan, Stefano Guido, Nadia L. Mitchell, David N. Palmer, C. Bruce A. Whitelaw, Jonathan D. Cooper, Thomas M. Wishart

Research output: Contribution to journalReview articlepeer-review

Abstract

Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models.

Original languageEnglish
Article number2641
JournalCells
Volume11
Issue number17
DOIs
StatePublished - Sep 2022

Keywords

  • clinical assessment
  • large animal model
  • model selection criteria
  • neurological disease

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