Grasping premanifest Huntington's disease - shaping new endpoints for new trials

Future clinical trials in subjects with premanifest Huntington's disease (preHD) may depend on the availability of biomarkers. It was previously shown in symptomatic HD that, the grip force variability coefficient-of-variation (GFV-C) in a grasping paradigm was correlated to the Unified-Huntington's-Disease-Rating-Scale-Total-Motor-Score (UHDRS-TMS) and increased in a 3 year follow-up study. To further elucidate its potential as a biomarker, we investigated whether GFV-C is able to detect a motor phenotype in preHD and is correlated to the genotype assessed by a disease-burden-score. The ability of preHD (n = 15) and symptomatic HD subjects (n = 20) to maintain stable grip forces, while holding an object (250 g and 500 g), was measured and compared with the controls (n = 19). GFV-C was increased in preHD at 500 g, in symptomatic subjects at both weights and was correlated to the disease-burden-score and UHDRS-TMS. GFV-C may be a useful objective and quantitative marker of motor dysfunction across genetically diagnosed premanifest and symptomatic HD subjects.