Mind the Gap: Models in Multiple Species Needed for Therapeutic Development in Huntington's Disease

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. (C) 2014 International Parkinson and Movement Disorder Society