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Oral presentations
A15 MRI brain imaging as a potential marker for Huntington's disease
  1. RI Scahill
  1. UCL Institute of Neurology, University College London, London, UK

Abstract

As disease-modifying treatment trials for HD become a realistic possibility, there is an urgent need to establish robust markers of disease progression with the potential to assess the efficacy of future neuroprotective agents. Such measures need to be sensitive to disease-related change in early HD and ideally premanifest subjects, have the ability to track disease progression over time and be reproducible across sites. Current clinical rating scales lack sensitivity and are subject to floor or ceiling effects, particularly in premanifest subjects. However, neuroimaging techniques are showing promise for detecting disease-related changes in the brain even in the very earliest premanifest stages. Structural MRI allows in vivo assessment of the macroscopic effects of underlying neuropathology, namely neuronal damage and ultimately brain atrophy. Large-scale multi-site studies such as TRACK-HD and PREDICT-HD have identified reliable measures such as striatal and white-matter atrophy with the ability to track disease progression in both early HD and even the premanifest stages, over timescales which are feasible for clinical trials. Such measures have already been applied to trials of novel therapies in conditions such as Alzheimer's disease and multiple sclerosis. I will discuss imaging metrics which might prove useful for future clinical trials in HD, together with the quality control and validation measures necessary for multi-site studies. I will present effect sizes and sample size estimates and also discuss the relationship of imaging measures to functional readouts.

Funding Rachael Scahill is supported by the CHDI Foundation, a not for profit organisation dedicated to finding treatments for HD.

  • MRI
  • imaging
  • biomarkers

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