Abstract

Biomarkers in HD

Rachael Scahill, Senior Research Associate, Microscience Ltd

Huntington’s disease (HD) is a devastating inherited neurodegenerative disease for which there are currently no effective disease-modifying treatments. However, considerable progress is being made towards this goal with encouraging results from in vitro studies and animal models; consequently robust outcome measures to assess therapeutic efficacy are urgently needed.Current clinical rating scales lack sensitivity and are subject to floor or ceiling effects, particularly early in the disease process. Large observational multi-site studies such as TRACK-HD and PREDICT-HD are investigating a variety of potential biomarkers such as cognitive, motor and neuropsychiatric measures as well as novel imaging methodologies. Neuroimaging is becoming increasingly used as an FDA-approved outcome measure for trials in a range of neurodegenerative conditions such as Alzheimer’s disease. High resolution structural imaging allows in vivo assessment of the macroscopic effects of underlying neuropathology. In accordance with neuropathological evidence, imaging has demonstrated volume reduction in the striatum, as well as widespread grey and white matter loss and cortical thinning in early HD and even in gene-positive carriers prior to overt symptom onset. More recently, diffusion-tensor imaging has revealed disease-related degeneration of white matter tracts and functional imaging studies have also highlighted early neuronal dysfunction. A range of PET ligands are also being investigated in HD, with the aim of identifying disease-specific processes which may suitable targets for drug development.These studies are providing essential information on the utility of these imaging methods across sites and their relationship with clinical measures, thereby informing the design of future therapeutic trials for HD.