A Rapid Neurobehavioral Assessment Reveals that FK506 Delays Symptom Onset in R6/2 Huntington's Disease Mice
S. Ditzler, J. Stoeck, M. LeBlanc, C. Kooperberg, S. Hansen, L. Coppin, and J.M. Olson

Abstract
Numerous drugs improve survival of R6/2 Huntington's disease mice by 10%-20%. The use of survival as the primary endpoint for these preclinical trials is problematic because one would not wish to prolong the symptomatic phase of Huntington's disease. Additional measures of weight maintenance, rotarod performance, and pathologic leg clasping capture only a fraction of the information about the well-being of mice. To improve the ability to identify drugs that delay onset of neurologic symptoms, we developed a rapid neurobehavioral phenotype assessment that scores for tremors, grooming, spontaneous activity, and locomotor activity in addition to rotarod performance and pathologic clasping. Prospective utilization of this assessment as the primary endpoint for preclinical efficacy studies revealed that the neuroprotective agent, FK506, delayed symptom onset in R6/2 mice without prolonging the symptomatic phase of disease.

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