Mind the gap: models in multiple species needed for therapeutic development in Huntington's disease

Mov Disord. 2014 Sep 15;29(11):1397-403. doi: 10.1002/mds.26008. Epub 2014 Aug 22.


Unraveling the pathophysiology and testing candidate therapeutics in neurodegenerative disorders is, necessarily, highly dependent on model systems. Because Huntington's disease (HD) is caused by a single (expanded CAG tract) mutation in the huntingtin (HTT) gene, a richness of model systems, particularly mice, have been engineered to both dissect disease mechanisms and test potential therapeutics. Even so, as with other neurodegenerative diseases, very little success has been achieved in translating HD mouse model drug testing results to the clinic. Because of the considerable costs-human, opportunity, and financial-there is a pressing need to improve the use of existing HD models and also to develop models in higher species beyond rodent, such as sheep, minipig, and nonhuman primate, to bridge the translational gap from preclinical to clinical testing of candidate therapeutics.

Keywords: animal model; huntingtin; minipig; nonhuman primate; sheep.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / therapy*
  • Nerve Tissue Proteins / genetics
  • Species Specificity
  • Translational Medical Research / methods*
  • Trinucleotide Repeats / genetics


  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins