Tapping in Huntington disease

The development of therapeutics aimed at delaying the onset or slowing progression of neurodegenerative diseases has been elusive. This is largely related to the challenges of identifying a homogenous cohort, the long time horizons associated with disease onset and progression, and the ability to identify outcome measures that reflect the underlying neuropathology of disease. Huntington disease (HD) is a prototypical adult-onset neurodegenerative disease that allows one to identify with 100% certainty a homogenous population years before the onset of clinical symptoms and therefore represents an ideal disease to explore therapeutic strategies aimed at delaying the onset of illness. However, even in HD, the ability to determine accurately whether a treatment has a meaningful effect on delaying disease onset remains challenging due to the low incidence of onset over relatively short study periods and the difficulty of measuring clinical signs in a population that is not yet ill. In this issue of Neurology®, Bechtel et al.¹ describe a quantitative motor task that links function and structure and distinguishes healthy controls from gene-positive individuals prior to disease onset through early stages of manifest HD. These findings suggest a path forward to designing therapeutic trials aimed at showing an effect on delaying onset in preHD or in …