Abstract

Since 2008 TRACK-HD has chronicled the earliest stages of the neurodegenerative disease processes in premanifest and mild to moderately symptomatic individuals who carry the Huntington's disease expansion mutation. TRACK-HD was designed to observe natural disease progression in premanifest and early stage HD with the aim to establish sensitive and specific clinical and biological markers of disease progression. Such markers potentially serve as a basis for eventually defining outcome measures for future disease-modifying therapeutic trials. We recently reported longitudinal effect sizes for disease-progression in early stage Huntington's disease over 24 months. Some of these 24 month data will be presented in this talk in more detail, including insights into what we have learnt about predictors of Huntington's disease progression in both premanifest and early stage subjects. Analysis of the 36 month data is ongoing; this new data will also be presented including a range of novel clinical measures that now show significant change in the premanifest group over this period. We have also identified baseline predictors of disease progression which may help enrichment for future disease-modifying clinical trials. We are also now in a position to model progression in a range of functional and imaging measures across the spectrum of disease. Finally I will briefly introduce our new study – Track-On HD – which aims to identify neural compensatory networks that may occur in the premanifest phase of neurodegeneration in HD. This study will test the hypothesis that functional reorganisation of networks may precede widespread structural loss in premanifest HD, and that symptom onset may reflect a decompensation of these neural compensatory networks.