Abstract

Professor Sarah Tabrizi is Professor of Clinical Neurology at UCL Institute of Neurology, and an Honorary Consultant Neurologist at the National Hospital for Neurology and Neurosurgery. After undergraduate degrees in Biochemistry and Medicine at the University of Edinburgh, Sarah undertook her PhD at UCL as an MRC Clinical Training Fellow studying the role of mitochondrial dysfunction in cellular neurodegeneration. After clinical training in Neurology, in 2002 she was awarded a 5-year MRC/DH National Clinician Scientist Fellowship, enabling her to establish her own research group, studying cellular mechanisms of neurodegeneration, concentrating on protein misfolding diseases, particularly prion disease and Huntington's disease. In 2006, she was awarded one of the first HEFCE New Blood Senior Lectureships; in 2007 she was promoted to Reader and in 2009 to Professor at UCL. In addition to bench science which focuses on cellular mechanisms of neurodegeneration, Sarah also leads a large translational research programme in Huntington's disease working towards finding treatments for this disease. Sarah is PI of TRACK-HD, a major international research initiative aimed at understanding the neurobiology of the neurodegenerative changes in premanifest and early stage HD gene carriers, which is essential for the development of disease-modifying therapies to treat this disorder. She also first described the role of the immune system as a modifier of Huntington's disease pathogenesis, and has an ongoing research interest in this area. Professor Tabrizi has had funding from the MRC, Wellcome Trust, CHDI/High Q Foundation, EU Framework 7, UK HD association, Brain Research Trust, Dementia and Neurodegenerative Diseases Network (Dendron) and the UCL/UCLH BRC for her research.

Huntington's disease (HD) is a neurodegenerative condition characterised by deterioration of motor and cognitive function as well as neuropsychiatric disturbance. The mean age of onset is 40 years, and progression is slow and inexorable, with death occurring typically 15–20 years later. It is inherited in an autosomal dominant manner, causing devastation to affected families. Currently there are no treatments available which modify disease progression. However, novel therapeutic agents specifically targeting HD pathology are now on the horizon.¹ TRACK-HD is an ongoing, large multi-national observational study which aims to investigate a range of potential biomarkers in premanifest HD gene carriers and early HD subjects which may have utility in clinical trials. Standardised data collection of state-of-the-art 3 T MR imaging and novel cognitive, quantitative motor, oculomotor, and neuropsychiatric assessments across four international sites has been achieved, with minimal dropout of subjects over a 3-year period. Baseline analysis of 123 controls, 120 premanifest gene carriers and 123 early HD subjects identified measures which were able to detect disease effects several years prior to symptom onset.² Follow-up analysis found that imaging measures were the most sensitive to change at all stages of the disease from premanifest to early HD³; these techniques were able to identify subtle changes over just 1 year in this slowly progressive, heterogeneous condition and consequently show promise as potential biomarkers for future therapeutic trials. TRACK-HD is also undertaking genetic, biochemical and epigenetic profiling of all subjects to help identify key modifiers of the pathogenic disease process. Data from TRACK-HD has been presented at meetings of the European Medicines Agency and FDA (8th November 2010 Expert meeting in familial neurodegenerative disorders London) as an example of how international collaborative studies can set the benchmark towards identifying outcomes measures to test novel therapies in subjects many years before symptom onset, or with very early disease. TRACK-HD has advanced our understanding of both the clinical manifestation and underlying pathobiology of HD in the earliest phase of the neurodegenerative disease process, such that we are now better-equipped to enter disease-modifying clinical trials and offer hope to the families affected by this devastating disease.