Targeting the innate immune system in Huntington's disease

Lead Research Organisation: University College London
Department Name: Institute of Neurology

Abstract

Huntington's disease (HD) is a fatal, inherited neurological condition. The earliest symptoms are often subtle problems with mood or cognition, followed by a lack of coordination and an unsteady gait. As the disease progresses, jerky body movements become more apparent, along with a decline in mental abilities and behavioural and psychiatric problems. Affected individuals also suffer progressive weight loss and muscle wasting. The disease typically progresses over several decades until death. There are a few effective treatments for some of the symptoms, but there is no cure that will halt or slow progression of the disease. The inherited nature of HD means that the children of affected individuals have a 50% chance of developing the disease themselves.

The disease is caused by a mutation in a single gene that encodes for a protein called huntingtin (HTT). The only difference between the mutated and normal versions of the gene is an increase in the number of repeats of the DNA sequence CAG close to its beginning. This causes an increase in the number of glutamines (an amino acid, the building blocks of proteins) in the HTT protein. This causes the HTT protein to behave in an aberrant fashion in the cells in which it's made.

HD is primarily thought of as disease of the brain, but the HTT protein (both the mutant and normal forms) is expressed in all the cells of the body. It is becoming increasingly recognised that there are significant changes outside of the brain in HD, including in muscle, heart, fat and, of interest here, the immune system. In fact, people carrying the HD gene show signs of increased inflammation, as shown by elevated levels of certain molecules in their blood. Beyond the urgent need for new therapies, one advantage of studying HD is that genetic testing can establish with 100% accuracy whether an individual carries the mutant gene or not, enabling us to study the disease before an individual develops any symptoms. In doing this, we have discovered that the increased inflammation in HD is observed many years before symptom onset. This suggests that inflammation might have long-term effects that are important in the development of the disease.

We have also discovered that inflammation in HD is probably due to the aberrant behaviour of a particular group of immune cells, called monocytes and macrophages. These cells are hyper-responsive to immune stimulation and produce excessive levels of the inflammatory molecules detected in the blood of HD patients. It is becoming clear that the immune system causes changes in the brain and other tissues. Hence, it is conceivable that elevated inflammation in HD patients might be contributing to some of the changes in the brain and/or other tissues that cause the symptoms of the disease to worsen. There are already safe treatments available that will reduce inflammation in humans, but this strategy has not yet been tried in HD.

Our aims are to determine whether inflammation really does contribute to HD progression and if so, whether we can use specific therapeutic agents to lower the inflammation to help treat the disease. We also want to discover the exact means by which the mutant HTT protein causes monocytes and macrophages to behave aberrantly, which may help identify alternative targets for developing treatments for HD.

To achieve these aims, we will undertake a range of experiments in cells from HD patients and in mouse models. We will determine exactly which genes are altered in HD monocytes and macrophages, and will attempt to discover how mutant HTT causes these changes to occur. We will treat HD mice with various agents that are expected to increase or decrease their levels of inflammation, including drugs that reduce inflammation and are already used for this purpose to treat other diseases. We hope that any positive results from these studies will lead to clinical trials in HD patients.

Technical Summary

Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene, leading to an expanded poly-glutamine tract in the HTT protein. Considerable evidence suggests that HD is associated with increased systemic inflammation that may contribute to progression of the disease. We have shown previously that myeloid cells from HD patients are hyper-responsive to stimulation and that this is due to the intrinsic expression of the mutant HTT protein in these cells.

Our hypothesis is that mHTT primes myeloid cell hyper-reactivity to immune stimulation and that the resultant low-level systemic inflammation contributes to HD progression. We aim to determine the mechanisms by which mHTT affects myeloid cells isolated from the blood of HD patients as compared to those from non-HD individuals, by means of full-transcriptome sequencing and methods to monitor transcription factor activation and binding.

We also aim to establish the extent to which components of the peripheral innate immune system contribute to HD and to determine whether systemic inflammation can be targeted to modify disease progression. We will specifically target cells and pathways by genetic and/or pharmacological means in ways that might ameliorate aspects of disease, allowing us to dissect the contribution of specific cell populations, signalling pathways and molecules to HD progression. We hope this will form the basis of further work seeking therapeutic intervention that targets in peripheral innate immune system and systemic inflammation in HD.

Understanding the contribution that systemic inflammation makes to pathogenesis is essential in determining whether targeting it might be a viable therapeutic strategy in HD. A complete mechanistic understanding of these events may identify targets that lead to the development of novel therapies.

Planned Impact

The potential beneficiaries of our research include Huntington's disease patients and families, scientists and clinicians working on HD and/or neuroinflammation, as well as biotechnology and pharmaceutical companies with research and development and/or commercial interests in these areas.

For researchers, an improved understanding of neuroinflammatory events will aid all researchers with an interest in the pathogenic basis of HD. It will also have important implications for the potential development a new therapeutic strategy in HD. To that end, if results are positive, we expect to receive the active support of the CHDI Foundation (whose letter of support is enclosed), a not-for-profit research organisation that works with scientists internationally to discover therapies that slow the progression of HD. The discovery of such therapies will be of considerable commercial interest to companies working in this area.

For patients, we hope the work will form the basis of developing treatments for those who have developed or are likely to develop the disease. HD is a devastating disease that places an intolerable burden on those who suffer from the disorder and their families. The inherited nature of the disease means that family members who act as carers may be doing so with the absolute knowledge that they themselves are going to develop the disease later in life. There are currently no disease-modifying treatments for HD. Significant breakthroughs in our understanding of the pathogenesis of the disease conveys hope to patients and families, and will encourage participation in clinical trials. Understanding the mechanistic underpinnings of the disease will assist in the development of treatments for the benefit of patients.

More widely, the discovery of underlying pathogenic processes and/or therapeutic targets in one neurodegenerative disorder offers hope for researchers working on and patients affected by many others. Neurodegenerative disease is having a serious and long-term impact on an aging UK population, with effects extending from the immeasurable burden on the lives of those affected, to the wider social and economic implications of long-term care. Studies estimate that neurodegenerative disease already costs the UK economy more than cancer and heart disease combined. Due to the likely irreversible nature of the neuronal loss during neurodegeneration, therapies need to target the pre-degenerative disease state. Research in HD, for which there is predictive genetic test that can establish with absolute certainty whether a person will develop the disease later in life, may form the basis of the development of preventative treatments in other neurodegenerative disorders.

Finally, this grant will provide Ralph Andre with the resources to capitalise on his work to date on neuroinflammation as a modifier of disease in HD. He has made a large contribution to the preparation of this grant application; this funding will allow him to build a highly competitive CV from which he can launch his independent career. It will benefit the field by ensuring that a highly capable young investigator is committed to work on HD for the foreseeable future.

Publications

10 25 50
 
Description EXPLORING THE ROLE AND THERAPEUTIC POTENTIAL OF RAB GTPASES IN HUNTINGTON'S DISEASE
Amount £759,052 (GBP)
Funding ID MR/R011621/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2018 
End 02/2021
 
Description High Content Screening (HCS) platform for HD drug discovery
Amount £381,185 (GBP)
Organisation Takeda Pharmaceutical Company 
Sector Private
Country Global
Start 12/2017 
End 12/2019
 
Title Patient-derived cell lines 
Description Fibroblasts, lymphoblasts and stem cells 
Type Of Material Biological samples 
Year Produced 2017 
Provided To Others? No  
Impact Ongoing research into genetic modifiers and inflammation in HD 
 
Title RNA sequencing 
Description Primary human monocyte RNAseq from HD patients. RNAseq performed by deCODE, available within the NeurOmics consortium. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Published in Human Molecular Genetics 
 
Description Andreas Weiss 
Organisation Evotec
Country Germany 
Sector Private 
PI Contribution Intellectual contribution and reagents
Collaborator Contribution Intellectual contribution and reagents
Impact None as yet
Start Year 2011
 
Description Dr Paul Lavender 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual contribution and reagents
Collaborator Contribution Intellectual contribution and reagents
Impact None as yet
Start Year 2014
 
Description Dr Vincent Plagnol 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual contribution and data analyis
Collaborator Contribution Intellectual contribution and data analysis
Impact None as yet
Start Year 2015
 
Description Professor David Greaves 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual contribution
Collaborator Contribution Intellectual contribution and reagents
Impact None as yet
Start Year 2014
 
Description Professor Flaviano Giorgini 
Organisation University of Leicester
Department Department of Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-application for funding
Collaborator Contribution Co-application for funding
Impact Award of funding, MRC:Research Grant EXPLORING THE ROLE AND THERAPEUTIC POTENTIAL OF RAB GTPASES IN HUNTINGTON'S DISEASE Professor Flaviano Giorgini:University of Leicester MR/R011621/1
Start Year 2018
 
Description Professor Gillian Bates 
Organisation King's College London
Department School of Medicine KCL
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual Contribution and Reagents. Running in vivo aspects of the project.
Collaborator Contribution I was co-applicant on this grant. As well as funding there was intellectual contribution and reagents
Impact Gill Bates - she has been collaborating with Gill Bates since 2000 and is co-applicant on another MRC grant with Gill Bates: 3 papers from 2006 are: Tsang T, Woodman B, McGloughlin G, Griffin J, Tabrizi SJ, Bates GP, Holmes E. Metabanomic Characterisation of the R6/2 Transgenic Mouse Model of Huntington's Disease by High-Resolution MAS 1H NMR spectroscopy. Journal of Proteome Research. 2006 Mar;5(3):483-92. Alexandra Zourlidou, Tali Gidalevitz , Mark Kristiansen , Ben Woodman, Dominic J. Wells, David S. Latchman, Jackie de Belleroche, S. J. Tabrizi, Richard I. Morimoto and Gillian P. Bates. Hsp27 overexpression in the R6/2 mouse model of Huntington's Disease: Chronic Neurodegeneration does not Induce Hsp27 Activation. Human Molecular Genetics. Epub 2007 Mar 14. 2007 May 1;16(9):1078-90. Annette Dalrymple, Edward J Wild, Richard Joubert, Kirupa Sathasivam, Maria Björkqvist, Åsa Petersén, Jeremy Isaacs, Mark Kristiansen, Gillian P Bates Blair R Leavitt, Geoff Keir, Malcolm Ward, S. J Tabrizi. Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and candidate biomarkers Journal of Proteome Research. 2007 Jul;6(7):2833-40. 2008 -2011 Identification and Cross-validation of Early Stage Phenotypes in Mouse Models of Huntington's disease. Ref G0800846 - MRC - Models of Disease grant. Co-applicant with Professor Gillian Bates (PI) and Dr Michael Modeo (co-applicant). £910,736
Start Year 2008
 
Description Professor Lesley Jones 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual contribution
Collaborator Contribution Intellectual contribution and reagents
Impact None as yet
Start Year 2015
 
Description Professor Neil Aronin 
Organisation University of Massachusetts
Country United States 
Sector Academic/University 
PI Contribution Intellectual contribution and reagents
Collaborator Contribution Intellectual contribution and reagents
Impact Träger U, Andre R, Lahiri N, Magnusson-Lind A, Weiss A, Grueninger S, McKinnon C, Sirinathsinghji E, Kahlon S, Pfister EL, Moser R, Hummerich H, Antoniou M, Bates GP, Luthi-Carter R, Lowdell MW, Björkqvist M, Ostroff GR, Aronin N, Tabrizi SJ. HTT-lowering reverses Huntington's disease immune dysfunction caused by NF?B pathway dysregulation. Brain. 2014 Mar; 137 (Pt 3):819-33.
Start Year 2012
 
Description Professor Peter Holmanns 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual contribution and reagents
Collaborator Contribution Intellectual contribution and reagents
Impact None as yet
Start Year 2015
 
Description 2018 UCL Neuroscience Symposium, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact 2018 UCL Neuroscience Symposium, London, UK (June). Presented talk 'Antisense oligonucleotide therapy for Huntington's disease - results from the first HTT lowering clinical trial'. Generated questions and interest in HD trials
Year(s) Of Engagement Activity 2018
 
Description Brains Talk Seminar at Roche 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Presented seminar on Hutington's Disease to Roche Pharmaceuticals to aid company strategic planning
Year(s) Of Engagement Activity 2015
 
Description Cotzias Prize Lecture - LXX Annual Meeting of the Spanish Society of Neurology (SEN 2018), Gran Sevilla Events Center, Seville, Spain 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk on to Spanish Neurological Society: 'Huntington's disease: natural history, biomarkers and novel therapeutic horizons'
Year(s) Of Engagement Activity 2018
 
Description Discussion leader at 'Molecules to Humans' session at CAG Triplet Repeat Disorders Gordon Research Conference (GRC) Conference, USA 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented talk titled: 'Molecules to Humans'. Generated questions from audience members
Year(s) Of Engagement Activity 2017
 
Description Distinguished Lecture Series, University of Leuven, Belgium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Distinguished Lecture Series, University of Leuven, Belgium. Talk titled: Meeting the therapeutic challenge of Huntington's disease. Generated questions and further interest in research
Year(s) Of Engagement Activity 2019
 
Description FIL Brain Meeting, UCL, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact FIL Brain Meeting, The Wellcome Centre for Human Neuroimaging, UCL London, UK. Presented talk 'meeting therapetic challenge of Huntignton's disease'. Talk generated discussion and lively debate.
Year(s) Of Engagement Activity 2018
 
Description Genetic Therapies in Neurodegeneration: Cohorts, Targets and Approaches Symposium, UCL London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Genetic Therapies in Neurodegeneration: Cohorts, Targets and Approaches Symposium, UCL, London, UK (May). Talk titled' Huntington's disease, results from the IONIS HTT Rx CS1 study - the first HTT lowering clinical trial'. Generated questions and interest in HD trials.
Year(s) Of Engagement Activity 2018
 
Description Great Ormond Street Hospital Neurosciences Meeting, London, UK (October) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Great Ormond Street Hospital Neurosciences Meeting, London, UK. Talk titled: Meeting Therapuetic Challenge of Huntington's Disease. Sparked questions and interest in involvement in clinical trials
Year(s) Of Engagement Activity 2018
 
Description HD Website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Articles of this nature serve to enhance engagement with my research

Positive feedback from patients and healthcare professionals
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Interview/profile in Lancet Neurology 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Professor Sarah Tabrizi completed a profile interview in the Lancet Neurology. Helps raise the profile of her research and the UCL HD Centre.
Year(s) Of Engagement Activity 2017
URL http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(17)30303-4/abstract
 
Description Lecture at the Young European Scientists meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact Approximately 400 young scientists from across Europe at a conference to discuss a wide range of topics in the biological and medical sciences
Year(s) Of Engagement Activity 2017
 
Description Medicine at the Crick Inaugural Event - Gene and Genome Editing Therapy: A new challenge and opportunity in Clinical Medicine, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Medicine at the Crick Inaugural Event - Gene and Genome Editing Therapy: A new challenge and opportunity in Clinical Medicine, London, UK. Talk titled: 'Huntington's disease: RNA targetting therapy and prospects of gene therapy'. Talk generated questions and widened interest in HD research
Year(s) Of Engagement Activity 2018
 
Description Observer news article on Huntington diseae trials 03/03/2019 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article on Huntington's disease therapies at current clinical trail. https://www.theguardian.com/science/2019/mar/03/huntingtons-disease-new-drug--families. Increased awareness of HD and generated interest in trial.
Year(s) Of Engagement Activity 2019
URL https://www.theguardian.com/science/2019/mar/03/huntingtons-disease-new-drug--families
 
Description Plenary Lecture at 15th Annual Update Conference on Clinical Neurology and Neurophysiology, Tel Aviv, Israel (February) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary Lecture at 15th Annual Update Conference on Clinical Neurology and Neurophysiology, Tel Aviv, Israel. Talk title: Meeting the therapeutic challenge of Huntington's Disease. Form genetic modifiers to the first trial of antisense therapy. Talk presented by Prof Lanwehermeyer due Prof Tabrizi illness. Additional talk presented to patient and family groups. Generate questions and further interest in HD research trials.
Year(s) Of Engagement Activity 2019
 
Description Plenary Lecture at British Society for Genetic Medicine Annual Conference - UK Clinical Genomics 2018, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Plenary Lecture at British Society for Genetic Medicine Annual Conference - UK Clinical Genomics 2018, London. Talk entitled: `Meeting the therapeutic challenge of Huntington's disease'. Generated questions and interest in research and trials
Year(s) Of Engagement Activity 2018
 
Description Plenary Lecture at the 10th EHDN Plenary Meeting, Vienna, Austria 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary Lecture at the 10th EHDN Plenary Meeting, Vienna, Austria. Presented results of ongoing HTT lowering trials to scientists, patients, industy. Generated questions and interest in developing/participating the clinical trial
Year(s) Of Engagement Activity 2018
 
Description Plenary Lecture at the ABN 2018 Annual Meeting, Birmingham, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Plenary Lecture at the ABN 2018 Annual Meeting, Birmingham, UK. Talk titled: 'Antisense oligonucleotide therapy for Huntington's disease - results from the first HTT lowering clinical trial'. Generated questions and interest in HD trials
Year(s) Of Engagement Activity 2018
 
Description Plenary Lecture at the Alzheimer's Society Annual Conference, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Plenary Lecture at the Alzheimer's Society Annual Conference, London, UK. Presented talk entitled: Meeting the therapeutic challenge in Huntington's disease and other forms of dementia'
Year(s) Of Engagement Activity 2018
 
Description Plenary Lecture at the UK-Japan Neuroscience Symposium, Royal Society, London, UK (March) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary Lecture at the UK-Japan Neuroscience Symposium, Royal Society, London, UK; Presented talk titled: 'Meeting the therapeutic challenge in Huntington's disease'
Year(s) Of Engagement Activity 2018
 
Description Present talk at European Huntington's Disease Network Conference 2016, The Hague 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented talk entitled 'Gene targeting therapies for Huntington's disease'. Generated talk questions and audience discussion
Year(s) Of Engagement Activity 2016
 
Description Presented Seminar to Vertex Pharmaceuticals, Oxford 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Presented talk titled 'Huntington's Disease: An overview' providing overview of HD in the clinic, developments in the field, and insights into potentially fruitful avenues for future therapies.
Year(s) Of Engagement Activity 2017
 
Description Presented poster at European Huntington's Disease Network 2016 Conference, The Hague 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented poster titled: 'Abnormal bioenergetics in inclusion-containing mutant HTT exon 1 primary human neurons. Alison Wood-Kaczmar, Rhia Ghosh, Janos Kriston-Vizi, Edward Smith, Wayne Chadwick, Iain Hargreaves, Simon Heales, Andrey Abramov, Sarah Cole, Robin Ketteler, Gillian Bates, Ralph Andre, Sarah J Tabrizi.
Poster generated questions from attendees and discussions about future research plans.
Year(s) Of Engagement Activity 2016
 
Description Presented poster at European Huntington's Disease Network 2016 Conference, The Hague 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presentation of a poster titled 'Innate transcriptional dysregulation is associated with proinflammatory pathway activation in Huntington's disease myeloid cells. Ralph Andre, James RC Miller, Kitty K Lo, Davina J Hensman Moss, Ulrike Träger, Timothy C Stone, Peter McErlean, Lesley Jones, Peter Holmans, Paul Lavender, Vincent Plagnol and Sarah J Tabrizi
Generated questions from attendees and discussions about future plans
Year(s) Of Engagement Activity 2016
 
Description Presented poster at European Huntington's Disease Network 2016 Conference, The Hague 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented poster:
Ralph Andre1, James RC Miller1, Kitty K Lo2, Davina J Hensman Moss1, Ulrike Träger1#, Timothy C Stone3, Peter McErlean4, Lesley Jones3, Peter Holmans3, Paul Lavender4, Vincent Plagnol2 and Sarah J Tabrizi1. Innate transcriptional dysregulation is associated with proinflammatory pathway activation in Huntington's disease myeloid cells

Generated questions from attendees and discussions about future research plaans
Year(s) Of Engagement Activity 2016
 
Description Presented poster at European Huntington's Disease Network 2016 Conference, The Hague 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Preseented poster titled 'ASSESSMENT OF IMMUNE SYSTEM ACTIVATION STATUS DURING THE COURSE OF HUNTINGTON'S DISEASE IN HD MOUSE MODELS. Jeffrey Pido-Lopez, Ralph Andre, Agnesska Benjamin, Sophie A. Franklin, Sarah J. Tabrizi and Gillian P. Bates'
Poster generated questions and discussions about future research plans
Year(s) Of Engagement Activity 2016
 
Description Presented poster at Hereditary Disease Foundation Conference 2016, Boston 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented poster entitled 'Abnormal bioenergetics in inclusion containing mutant HTT exon 1 primary human neurons'. Generated questions from attendees.
Year(s) Of Engagement Activity 2016
 
Description Presented talk a Lancet Neurology Conference 2017, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented talk entitled 'Gene silencing approaches for Huntington's disease'. Generated questions and audience discussions.

Prof Tabrizi also organised this meeting
Year(s) Of Engagement Activity 2016
 
Description Presented talk at "20th International Congress of Parkinson's Disease and Movement Disorders, Berlin" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented talk entitled 'Complex phenotypes and genotypes - seeing the wood for the trees, presentation titled Huntington's disease and HD-like disorders'. Generated audience discussion and questions
Year(s) Of Engagement Activity 2016
 
Description Presented talk at 11th Warsaw International Medical Congress for Young Scientists, Medical University of Warsaw 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presented talk entitled ''Meeting the therapeutic challenge in Huntington's disease'. Generated questions and discussion with audience
Year(s) Of Engagement Activity 2016
 
Description Presented talk at 28th Cambridge Neuroscience Seminar, Cambridge University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Presented talk entitled 'Meeting the therapeutic challenge in Huntington's disease'
Year(s) Of Engagement Activity 2016
 
Description Presented talk at Association of British Neurologists Special Interest Group Meeting 2017, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented talk entitled "Silencing abnormal proteins". Generated discussion and questions from the audience
Year(s) Of Engagement Activity 2017
 
Description Presented talk at Division of Brain Sciences, Imperial College London, Charing Cross Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presented talk entitled "Meeting the Therapeutic Challenge in Huntington's disease". Talk generated questions and audience participation
Year(s) Of Engagement Activity 2016
 
Description Presented talk at Hereditary Disease Foundation, The Milton Wexler Celebration of Life Symposium 2017, Massachusetts 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented talk entitled 'Early Clinical Development of IONIS-HTTR'. Talk generated questions and audience discussion
Year(s) Of Engagement Activity 2016
 
Description Presented talk at Huntington Study Group Conference and Satellite Symposium, Nashville 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented talk entitled "Neuroimaging endpoints for HD studies and Track-HD data". Talk generated questions and audience discussion
Year(s) Of Engagement Activity 2016
 
Description Presented talk at Imperial College Neuroscience Society's Conference 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Presented talk titled 'Meeting the therapeutic challenge in Huntington's disease'. Generated questions and audience discussion
Year(s) Of Engagement Activity 2017
 
Description Presented talk at Oxford University Departmental Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Presented talk entitled 'Meeting the Therapeutic Challenge in Huntington's disease'. Generated questions from audience and discussion
Year(s) Of Engagement Activity 2017
 
Description Presented talk at UCL Clinical Genetics Society Spring Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented talk entitled 'An update on Huntington's disease and therapy development' to practitioners and post-grad students
Year(s) Of Engagement Activity 2009,2017
 
Description Presented talk at UCL SLMS 2016 Clinical Academic Trainees Symposium, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presented talk entitled 'Gene silencing approaches for Huntington's disease'. Talk generated questions and audience discussions.
Year(s) Of Engagement Activity 2016
 
Description Presneted talk at CASMI / UCLH BRC / UCL Personalised Medicine Domain Symposium 2017, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Presented talk entitled 'Cellular and gene therapies'. Generated questions and discussion with audience
Year(s) Of Engagement Activity 2017
 
Description Press conference at American Academy of Neurology Conference, Los Angeles following presentation of HTT lowering phase 1/2a clinical trial results. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Press conference at American Academy of Neurology Conference following presentation of HTT lowering phase 1/2a clinical trial results. Conference generated questions from media an a plethora of subsequent scientific news articles
Year(s) Of Engagement Activity 2018
 
Description Prof Raymund Roos Farewell Symposium - From bed to bench and back to the future: Huntington's disease, Leiden, The Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Prof Raymund Roos Farewell Symposium - From bed to bench and back to the future: Huntington's disease, Leiden, The Netherlands. Presented talk entitled 'The future clinics of Huntington's disease'. Generated questions and sparked debate,
Year(s) Of Engagement Activity 2018
 
Description Royal Society and Academy of Medical Sciences Conference `Delivering Novel Therapies in the 21st Century', London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Royal Society and Academy of Medical Sciences Conference `Delivering Novel Therapies in the 21st Century', London, UK. Presented talk entitled 'ASO Therapies for Huntington's Disease. Results from the first HTT lowering trial'. Talk generated discussion and further interest in clinical trial
Year(s) Of Engagement Activity 2018
 
Description Royal Society of Medicine 17th Medical Innovations Summit, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Royal Society of Medicine 17th Medical Innovations Summit, London, UK. Presented talk entiteld 'Meeting the therapeutic challenge of Huntington's disease'. Generated questions and interest in Huntington's disease reserach and trials
Year(s) Of Engagement Activity 2018
 
Description Seminar at UCB Pharma, Belgium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Talk and roundtable discussion at UCB Pharma on their potential involvement in Huntington's disease research and potential future collaboration.
Year(s) Of Engagement Activity 2018
 
Description Teaching to UCL MSc students 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Teaching to UCL post-graduate students
Year(s) Of Engagement Activity 2015,2016
 
Description UCL Medical Society, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact UCL Medical Society, London, UK. Presented talk entitled 'meeting therapeutic challenge of Huntington's disease'. Sparked lively debate and widen knowldege and interest in clinical trial
Year(s) Of Engagement Activity 2018
 
Description Wellcome Researcher Meeting: Neuroscience and Mental Health, Coventry, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Wellcome Researcher Meeting: Neuroscience and Mental Health, Coventry, UK. Talk titled: 'Antisense oligonucleotide therapy for Huntington's disease - results from the first HTT lowering clinical trial'.. Generated questions re HD research trials
Year(s) Of Engagement Activity 2018
 
Description Women in Science Seminar Series, University of Sussex Falmer, Brighton, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Women in Science Seminar Series, University of Science, Falmer, Brighton, UK. Presented talk titled 'meeting therapeutic challenge of Huntignton's disease'. Talk generated questions and interest in HD research
Year(s) Of Engagement Activity 2018
 
Description • DZNE Lecture Series 2018, Bonn, Germany 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact DZNE Lecture Series 2018, Bonn, Germany (June). Presented talk titled: Meeting the therapeutic challenge in Huntington's disease'. Generated interest in HD trials and questions about further collaboration
Year(s) Of Engagement Activity 2018