A team of researchers from UCL and the University of Cambridge led by Professor Sarah Tabrizi, Director of the Huntington’s Disease Centre, UCL Institute of Neurology, 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.

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. The drug is an antisense oligonucleotide (ASO) and is designed to instruct neurons to make less huntingtin protein.

The Wellcome Trust Collaborative Award 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 Gothenburg). ‘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.

The Wellcome Trust Award has three key aims, each working in parallel:

Aim 1

To understand the way in which brain cells recover and respond to ‘gene silencing’ treatment in Huntington’s disease.

The Award provides a unique opportunity to link with this first human ASO trial in HD to understand neurodegeneration, and in particular, how it is modified by treatment.

Aim 2

To develop a new generation of ASO treatments.

Co-applicant and co-director of the UCL HD Centre – Professor Gillian Bates – 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.

Aim 3

To determine when such therapies should be given to patients through the Huntington’s Disease Young Adult Study (HD-YAS).

We 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. See Current Studies HD-YAS for more information.

‘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, the Centre for Medical Imaging Computing and the FARR Institute of Health Informatics Research, 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.

Want to find out more?

Please contact Jessica Lowe, Jessica.lowe@ucl.ac.uk or call 0203 108 7539


Updated May 5, 2017