UCL HUNTINGTON’S DISEASE RESEARCH

INFORMATION FOR SCIENTISTS, CLINICIANS, PATIENTS, RELATIVES AND CARERS

UCL HUNTINGTON’S DISEASE RESEARCH

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.

Latest Huntington’s disease research news, provided by HDbuzz

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UCL Huntington’s Disease Research Fund

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.

 

Latest news

18th November, 2016 - Bates Lab

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.

Professor Gillian Bates FMedSci FRS

Professor Gillian Bates FMedSci FRS

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.

18th November, 2016 - The UCL Huntington’s Disease Centre

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 unparalled team of experts will spearhead a new era of disease-modifying therapeutics for HD.

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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.

15th July, 2016 - Dr Ed Wild talks about Huntington’s disease on Woman’s Hour

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).

womanshour

9th June, 2016 - Professor Sarah Tabrizi, Director of UCL’s Huntington’s Disease Centre, gives keynote speech at Google’s Zeitgeist event

Professor Sarah Tabrizi, Director of UCL’s Huntington’s Disease Centre, recently gave a keynote speech at Google’s Zeitgeist event. Zeitgeist events are high-profile gatherings, attended by some of the finest global leaders and thinkers. The theme of this year’s event was ‘The Next Giant Leap’ and Professor Tabrizi’s speech focused on how research on a genetic dementia, like Huntington’s disease, may not only offer hope to those who carry the Huntington’s gene, but also unlock treatments for other more complex dementias such as Alzheimer’s disease. The event, which was attended by approximately 200 people and available to stream online, was an excellent opportunity to bring significant attention to Huntington’s disease and the research being conducted by Professor Tabrizi and the HD Centre. You can watch Sarah’s inspirational speech on Zeitgeist Minds, here – https://www.zeitgeistminds.com/talk/6067962410696704/sarah-tabrizi-the-human-revolution-sarah-tabrizi.

17th February, 2016 - Major Wellcome Trust award to UCL boosts Huntington’s disease research

UCL today announced that a team of researchers from UCL and the University of Cambridge led by Professor Sarah Tabrizi, Director of UCL’s Huntington’s Disease Centre, have been granted a prestigious Wellcome Trust Collaborative Award in one of the largest investments in Huntington’s Disease (HD) ever given by a public funding body in the UK (see http://www.ucl.ac.uk/ion/articles/news/20160216 and www.wellcome.ac.uk/Funding/Biomedical-science/Funding-schemes/Science-collaborative-awards/index.htm). The 5-year, £3.4 million investment will support research to help our understanding of disease mechanisms in HD and, importantly, their response to treatment. This valuable work will in turn provide insights into other more common neurodegenerative diseases.

Huntington’s disease is a devastating inherited neurodegenerative condition for which there is currently no effective treatment to slow down the disease process. It is caused by a single faulty gene resulting in the build-up of a toxic protein – mutant huntingtin – which damages brain cells, leading to abnormal involuntary movements, psychiatric symptoms and dementia. In September 2015, a ground-breaking ‘gene silencing’ trial started, with Professor Tabrizi as the Global Chief Clinical Investigator working in partnership with Ionis Pharmaceuticals (http://hdresearch.ucl.ac.uk/2015/10/first-patients-treated-with-gene-silencing-drug-isis-httrx-for-huntingtons-disease-2/). The drug is an antisense oligonucleotide (ASO) and is designed to instruct neurons to make less huntingtin protein.

Many of the harmful processes which are involved in HD are also important in other more common neurodegenerative conditions such as Alzheimer’s disease. For this reason, HD provides an ideal model for general neurodegenerative mechanisms, with the potential to benefit a huge number of patients worldwide. The Wellcome Trust Collaborative Award provides a unique opportunity to link with this first human gene silencing trial in HD to understand neurodegeneration and in particular how it is modified by treatment. It builds on key collaborations with co-applicants Professor Geraint Rees at the Wellcome Trust Centre for Neuroimaging, Dr Gary Zhang (UCL Department of Computer Science and Centre for Medical Image Computing) and Professor Henrik Zetterberg (UCL and University of Gothenberg). ‘This is an exciting opportunity to link cutting edge neuroscience with the novel development of therapies in HD to better understand mechanisms of neural recovery in humans’ said Professor Rees.

Working in parallel, co-applicant Professor Gillian Bates – who will be moving to UCL in 2016 to be the co-director of the UCL HD centre – will explore alternative ASO treatments to provide the next generation of therapies for HD patients. She will use mouse models of HD to develop and test novel compounds targeting the most toxic forms of the protein. These approaches could potentially slow down the disease process.

The ultimate aim of HD research is to prevent the disease developing by treating gene carriers from the very earliest stage. The third strand of the WT award will examine young adult gene carriers, decades before expected disease onset, in order to identify the best time to intervene with therapy. The collaborative team will use brain imaging and novel cognitive tests (CANTAB and EMOTICOM), developed by co-applicants Professors Trevor Robbins and Barbara Sahakian at the University of Cambridge, to determine when the first signs of the disease can be detected.

‘For the first time we have a realistic chance of finding treatments which actually slow down the disease process. Ideally we aim to administer the most successful therapies to gene carriers years before widespread damage has occurred, with the hope that we can prevent or at least significantly delay disease onset,’ said Prof Tabrizi.

This ambitious project will be one of the first to be conducted in the newly-established Huntington’s Disease Centre, led by Professor Tabrizi and Professor Bates. This facility is well-placed at the UCL Institute of Neurology to benefit from links within UCL to the Leonard Wolfson Experimental Neurology Centre, the Wellcome Trust Centre for Neuroimaging and the Centre for Medical Imaging Computing, collaborations with the Universities of Cambridge and Iowa and support from industrial partners Ionis Pharmaceuticals, Evotec, Cambridge Cognition and IXICO plc as well as the charitable organisation, CHDI Foundation Inc.

Professor Tabrizi has strong links with the HD community and is passionate about the critical role they play in research. ‘It is an extremely exciting time to be involved in HD research and an important factor in getting to this point has been the tireless devotion of our fantastic HD families’ she said. Cath Stanley, Chief Executive of the Huntington’s Disease Association, welcomed the news saying ‘I am delighted that Professor Tabrizi has received this important award. This study will deliver much-needed insights into the mechanisms underlying Huntington’s disease. The opportunity to link with the hugely important gene silencing trial will also help our understanding of how treatment may slow disease progression which will be of great benefit to the HD community worldwide.’