Sarah J Tabrizi
BSc (Hons) MBChB (Hons) FRCP PhD FMedSci
Professor of Clinical Neurology
This site aims to bring together information about our research projects in Huntington’s disease (HD) for patients, family members and health professionals.
Through the Huntington’s Disease Multidisciplinary Clinic of the National Hospital for Neurology and Neurosurgery, we offer expert care and involvement in cutting-edge research, including clinical trials and work to understand HD and develop new treatments.
Our group is the largest and most productive clinically-focused HD research group in the UK.
We are delighted to accept donations to support our research, to help us understand and treat Huntington’s disease. Please donate via our UCL fundraising page.
We are delighted to announce that the UCL Huntington’s Disease Centre, UCL Institute of Neurology, was officially opened on 1 March by UCL President and Provost Professor Michael Arthur.
Directed by Professor Sarah Tabrizi FMedSci and co-directed by Professor Gill Bates FRS, and bringing together expertise from many disciplines, the Centre is uniquely placed worldwide to translate mechanistic insights into first-in-human studies in HD.
The Centre will answer important questions of early diagnosis and mechanistic understanding which will help refine and redefine disease, preparing for precision medicine and driving therapeutic innovation.
Professors Tabrizi and Bates, who together are world leaders in bench-to-bedside Huntington’s disease (HD) research, will be working alongside Dr Ed Wild, a new Principal Investigator in the Centre.
Tabrizi and Bates have already made considerable contributions to every aspect of HD research, from gene identification, underlying molecular mechanisms, animal modelling, therapeutic target validation and experimental medicine. Their basic science research programmes are focussing on the identification and validation of therapeutic targets that are proximal to the HD mutation and one of the first screening assays to be established by the ARUK DDI at UCL will be based on their work.
“I am delighted to have been recruited to UCL to establish the HD Centre with Prof Tabrizi. Our combined research programmes underpin all aspects of the translational pipeline, and will enable the HD Centre to make a significant contribution to the development of treatments for HD”. Professor Gill Bates, Co-Director of UCL Huntington’s Disease Centre
It is this translational research approach that will underpin the Centre’s overarching aim to develop and test effective therapies for HD, and to set the ground work to eventually prevent the clinical disease occurring completely
Linking with the Leonard Wolfson Experimental Neurology Centre (LWENC), the Centre is able to conduct first in man and proof-of-concept studies in patients prior to initiating larger phase 2 and 3 clinical trials, including their novel huntingtin-lowering trials.
“The creation of the UCL HD centre comes at a key time in HD research with potential disease modifying gene silencing trials in phase 1 with more in the pipeline. This bench-to-bedside research approach will underpin our aim to develop and test effective therapies for HD that prevent the clinical disease occurring. We believe we are pivotally placed to be able to translate effective therapies to patients affected by this terrible disease”. Professor Sarah Tabrizi, Director of UCL Huntington’s Disease Centre
“The lessons taken from the Centre’s impressive work will also help our wider understanding of neurological diseases and dementia, and link with the aims of the Institute of Neurology and the UCL led UK Dementia Research Institute: to transform the pace and power of research to find treatments for neurological diseases”. Professor Mike Hanna, Director of the UCL Institute of Neurology
Image: Provost Michael Arthur and HD family member Amanda Staveley
Professor Flaviano Giorgini has been named an Honorary Professor of University College London in the Institute of Neurology and UCL Huntington’s Disease Centre. The appointment – which will be in effect for 5 years – builds upon joint MRC-funded studies with Professor Gillian Bates and collaborative work with Professor Sarah Tabrizi and Dr Edward Wild.
Giorgini is Professor of Neurogenetics at the Department of Genetics, University of Leicester, and his research is focused upon understanding the molecular mechanisms underlying neurodegenerative disorders such as HD, with the goal of using this information to inform novel therapeutic strategies. His current HD-related work explores the contributions of the kynurenine pathway, mitochondrial dysfunction, and vesicle trafficking alterations to disease pathogenesis. He is also interested in the role of the Parkinsonian protein DJ-1 in neurodegeneration and alpha-synuclein mediated vesicle trafficking defects in Parkinson’s disease. He is chair of the Science and Bioethics Advisory Committee of the European HD Network and a member of Parkinson’s UK Grant Assessment Panel.
Professor Gillian Bates joins the Institute of Neurology, University College London.
Professor Gillian Bates has joined the Sobell Department of Motor Neuroscience from King’s College London where she was Head of the Division of Genetics and Molecular Medicine. She has been at the forefront of Huntington’s disease research for many years and has joined UCL to Co-Direct the Huntington’s Disease Research Centre with Professor Sarah Tabrizi.
The research of the Bates lab is focused on understanding the molecular basis of Huntington’s disease (HD) and developing therapeutic interventions. Toward this aim, we work closely with the research group of Professor Tabrizi, within the Huntington’s Disease Research Centre (www.hdresearch.ucl.ac.uk). Huntington’s disease is a devastating inherited neurodegenerative disorder that affects movement and cognition and is ultimately fatal. For more information about the Huntington’s disease multidisciplinary clinic, led by Professor Tabrizi, please visit http://hdresearch.ucl.ac.uk/hd-clinic/ and for an overview of research into HD please visit HDBuzz (http://en.hdbuzz.net/).
The mutation that causes Huntington’s disease is the expansion of a CAG repeat in the huntingtin (HTT) gene that leads to an abnormally long polyglutamine tract in the huntingtin protein (HTT). We are particularly interested in the direct effect of the mutation on HTT expression. We have found that the presence of the mutation results in the incomplete splicing of HTT resulting in the production of a small mRNA that encodes an exon 1 HTT protein. Exon 1 HTT has been shown to be highly pathogenic in a wide range of model systems. One programme of our research is directed toward understanding the molecular basis of the incomplete splicing event and determining the extent to which exon 1 HTT contributes to disease pathogenesis. We are conducting a preclinical assessment of approaches by which the generation of this small mRNA species could be prevented.
We use genetic and pharmacological approaches to validate therapeutic targets in mouse models of Huntington’s disease and over the past 10 years, have published a number of in vivo experiments which indicate that Huntington’s disease is caused by an aggregated, and not a soluble, form of the HTT protein. We are specifically interested in targeting the early stages of HTT aggregation, however, very little is known about the structure of the seeding competent aggregates that form in vivo. We are currently working with Prof. Erich Wanker (Berlin) and Dr. Gabriele Kaminski Schierle (Cambridge) to better understand the seeding and aggregation process.
The UCL Huntington’s Disease Centre
A Huntington’s Disease Centre has been established at University College London and will officially open in March 2017. It is directed by Professor Sarah Tabrizi and co-directed by Professor Gillian Bates, who has recently been recruited to UCL. Professor Tabrizi and Professor Bates will be working alongside Dr Ed Wild, a Principal Investigator in the Centre with a research group supported by an MRC Clinician Scientist Fellowship and CHDI Foundation.
The new UCL Huntington’s Disease Centre is uniquely placed world-wide to translate mechanistic insights to ‘first in human’ studies, led by Professors Tabrizi and Bates who together are world leaders in bench-to-bedside HD research. Within a single purpose-built facility, the Centre will bring together expertise from many disciplines, combining sophisticated cell-based systems, animal work, translational research and clinical trials. The Centre will answer important questions of early diagnosis and mechanistic understanding which will help refine and redefine disease, preparing for precision medicine and driving therapeutic innovation. Linking with the Leonard Wolfson Experimental Neurology Centre (LWENC), the HD Centre is able to conduct small proof-of-concept studies in patients prior to initiating larger phase 2 and 3 clinical trials, including novel huntingtin-lowering trials. In this way we anticipate that our unparalleled team of experts will spearhead a new era of disease-modifying therapeutics for HD.
The Huntington’s Disease Research Centre logo depicts a human figure composed from two intertwining strands, evoking the DNA we inherit from each parent. The figure is leaping forwards – a reference to the dance-like involuntary movements seen in people with Huntington’s disease – into a hope-filled future free from the disease.
Our own Dr Ed Wild appeared on BBC Radio 4 today, talking on Woman’s Hour about Huntington’s disease with Jenni Murray and a brave and inspiration HD family member, Susan Fletcher. Ed, who is a senior researcher in the HD team and a consultant neurologist at the National Hospital for Neurology and Neurosurgery, talked about Huntington’s, living with risk, talking to kids about HD, genetic testing and some of the exciting research that we are doing to fight Huntington’s. Listen to the full piece on the BBC iPlayer (starts at 8min 15sec).