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Title: Identification and evaluation of biomarkers for Huntington's disease
Author: Wild, E. J.
ISNI:       0000 0004 2732 3045
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2009
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Huntington’s disease (HD) is a devastating, incurable inherited neurodegenerative disorder that commonly affects adults in mid-life. Despite encouraging results from in vitro and animal trials, disease-modifying therapeutic trials in HD are limited by a lack of tools to track disease progression. HD is clinically heterogeneous, and current clinical rating scales lack sensitivity and specificity, particularly over relatively short time periods. Improvements in the precision of objective measurement of disease progression in HD could lead to state markers (biomarkers) better able to predict onset, detect progression and measure the effects of therapeutic intervention. Biomarkers capable of detecting disease-related changes in premanifest gene carriers will be essential for clinical trials of treatments to delay onset. Imaging, clinical and cognitive assessment as well as laboratory markers have all been proposed as biomarkers, but few measures have been quantified over short time intervals or shown to be predictive of clinical change over longer periods. A robust panel of biomarkers from a number of modalities will be necessary to progress to interventional clinical trials of disease-modifying therapies in HD, using biomarkers to measure the success or failure of an intervention. Such cross-validation requires simultaneous multimodal biomarker evaluation within a suitable cohort of subjects studied longitudinally. This thesis describes a multi-modal approach to the discovery and evaluation of potential biomarkers for Huntington's disease in a large cohort of human volunteers. After reviewing the relevant features of Huntington's disease and current state of biomarker research in Huntington's disease, several approaches to, and outcomes from, biomarker discovery and evaluation are described, including proteomic profiling, targeted ELISA, multiplex inflammatory profiling and measurement of whole-brain atrophy by longitudinal magnetic resonance imaging. The thesis draws together these different approaches and summarises the contributions to both biomarker research and our understanding of the neurobiology of HD that the work has generated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available