Major Wellcome Trust award to UCL boosts Huntington’s disease research
17 February 2016
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.
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.’