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A10 HD minipigs – behavioural and imaging protocols transitioning into preclinical trials
  1. Ralf Reilmann1,2,3
  1. 1George Huntington Institute, Münster, Germany
  2. 2Department of Radiology University of Muenster, Section for Neurodegeneration, Germany
  3. 3Hertie Institute for Clinical Brain Research, University of Tuebingen, Germany

Abstract

The role of large animal models in HD is currently under discussion and intense investigation. It is hoped that large animal models may improve the translational reliability of preclinical studies and deliver new perspectives for safety studies. Given several therapeutic approaches under development for HD that result in modifications which are not reversible this is of particular importance. In this talk we will review currently available transgenic and knock-in HD minipig models. Body size and metabolism are very similar to humans. The minipig brain size and anatomy allows for simulation of neurosurgical delivery pathways and assessment of vector distribution under more suitable conditions than, eg available in rodents. Longevity of the tgHD minipig model allows for follow-up studies of several years duration if desirable. Tests developed to assess motor, cognitive and behavioural phenotype of minipigs are introduced and data obtained from the tgHD Libechov minipig is discussed. MRI scans including anatomical, spectroscopic and diffusion weighted imaging (DWI) sequences will be presented including an initiative to generate a brain atlas for this model. The data obtained to date suggests that behavioural and comprehensive MR assessments are feasible with the Libechov tgHD minipig including long term follow-up studies with repetitive annual or bi-annual assessments. Several preclinical studies with the tgHD minipig model are ongoing or about to start. The scope, limitations and future perspectives of HD minipig models will be discussed.

  • minipig
  • MRI

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