Modelling neurological diseases in large animals: criteria for model selection and clinical assessment

Sam Eaton, Fraser Murdoch, Nina Rzechorzek, Gerard Thompson, Claudia Hartley, Benjamin Blacklock, Chris Proudfoot, Simon Lillico, Peter Tennant, Adrian Ritchie, James Nixon, Paul Brennan, Stefano Guido, Nadia L. Mitchell, David N. Palmer, Bruce Whitelaw, Jonathan D Cooper, Thomas 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 confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Im-proved 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, here 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
Pages (from-to)1-27
JournalCells
Volume11
Issue number17
DOIs
Publication statusPublished - 25 Aug 2022

Keywords

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

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