Cellular pathophysiology of prion-mediated neurodegeneration - a model for understanding protein misfolding disorders

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

Abstract

In the 1990s, scientists made a connection between bovine spongiform encephalopathy (BSE or "mad cow disease") and the fatal brain disorder variant Creutzfeldt-Jakob disease (vCJD) in humans. This discovery raised the profile of prion diseases both in the UK and internationally due to the associated public health and economic concerns. Rather than bacteria or viruses, prion diseases are caused by a rogue form of one our own proteins (prion protein), which accumulates in the central nervous system, leading to progressive brain cell malfunction and ultimately brain cell death. In patients, these changes appear as a rapidly advancing dementia, where memory, movement, balance and personality are all affected. In the absence of any effective treatment for prion disease sufferers, there is a clear need to study how the rogue prion protein leads to irreversible brain damage. It is becoming increasingly clear that the mechanisms underlying prion diseases are also observed in more common dementias such as Alzheimer's disease and Parkinson's disease. Our research therefore aims to investigate these similar pathways with the goal of identifying new drug targets for the treatment of all neurodegenerative conditions.

Previous work in our laboratory has identified that the rogue prion protein is able to block the cell's waste-processing centre (a structure known as the proteasome). Under normal conditions, the proteasome removes old or abnormally folded proteins from nerve cells to ensure they do not accumulate to toxic levels. By monitoring mice infected with prions we have observed that this disruption in cellular waste-processing occurs very early in disease progression. This suggests that drugs aimed at preserving this function in nerve cells could be candidates for future prion disease therapy. Our research therefore aims to answer two important questions: firstly, how do rogue prion proteins enter and move round inside the brain cells to disrupt normal waste-processing and secondly, what are the downstream consequences which lead to brain cell damage? The team uses a wide range of methods to answer these questions, including the detailed study of isolated cells and prion-infected laboratory mice. By furthering our understanding of how rogue prion proteins move around inside and damage the brain cells they infect, we hope to design treatments which aim to slow or prevent the onset of clinical symptoms in patients with prion disease and related neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease and Huntington's disease where similar pathways to nerve cell death exist.

Technical Summary

Prion diseases are fatal neurodegenerative disorders whose pathogenesis is associated with a conformational rearrangement of the normal cellular PrP (PrPC) to abnormal conformers (PrPSc) which causes neurodegeneration via a poorly defined mechanism. Understanding these mechanisms has key relevance to other neurodegenerative proteinopathies where both prion-like mechanisms and dysfunction of the proteostasis networks have been suggested to be important. My laboratory has demonstrated that dysfunction of the ubiquitin proteasome system (UPS) is an early event in prion disease pathogenesis in vivo, and that beta-sheet rich PrP oligomers potently inhibit proteasome activity in vitro. Work from my last MRC grant yielded a novel cell model where PrP knockdown neuroblastoma cells have been engineered to express an epitope-tagged PrP-chimera (PrP-Ala224MYC). This novel chimera is unique since it supports prion replication, and generates bona fide epitope-tagged PrPSc. We have used this model system to study the earliest events in prion infection. This proposal has five main aims directed at extending the understanding of the cellular pathobiology of prion disease. Our existing PrP-Ala224MYC cell model will be used to map the cellular trafficking pathways of PrPSc with a view to defining how it accesses the cytosol. We will reconstitute neuronal stem cells derived from PrP KO mice with PrP-Ala224MYC, to study prion formation, UPS dysfunction and cytotoxicity in neurons. Detailed biochemical studies will refine our molecular understanding of the inhibitory interaction between misfolded PrP and the UPS. Lentiviral-mediated knockdown of PrP in vivo will determine whether UPS activity can be modulated in neurons as a viable therapeutic target. A proteomic study of the ubiquitinated proteome in prion-diseased brain will identify substrate proteins that accumulate as the disease progresses with the aim of uncovering new pathways that may contribute to cellular toxicity.

Planned Impact

Neurodegenerative disease is set to have a serious and long-term impact on UK society, extending from the immeasurable burden on the lives of those affected to the wider social and economic implications of long-term care. The Dementia 2010 report estimated that neurodegenerative disease costs the UK economy £23 billion per year, greater than the cost of cancer (£12 billion/year) and heart disease (£8 billion/year) combined. To limit the inexorable rise in healthcare spending, research into neurodegeneration must uncover the sub-cellular mechanisms of disease to aid the design of rational therapeutics. Due to the irreversibility of neuronal loss, future therapies will need to target the pre-degenerative disease state, which is associated with subtle alterations in cellular function. Our research into the ubiquitin-proteasome system (UPS) has identified it as one of the earliest targets of prion-disease pathology. The proposed research will therefore investigate the relationship between misfolded proteins and the UPS to determine its validity as a therapeutic target. This research is of key interest to the pharmaceutical industry which, despite significant investment, has failed to date to develop effective disease-modifying treatments for patients with neurodegenerative diseases. By guiding the development of treatments for early stage dementia, our findings could help to shift public health policy away from long-term care and towards disease prevention.

Each of the specific research aims outlined in the scientific case for support will promote the development of new and innovative methodologies. For instance, the proposed research will continue to develop our novel engineered PrP chimera by using it to generate post-mitotic primary neuronal cultures which express a tagged PrPSc. Successful generation of this cell line will allow researchers to track the earliest sources of cellular toxicity following protein-misfolding - a key question which currently remainsanswered. Altered trafficking of misfolded proteins has been suggested to be of importance in several neurodegenerative diseases (e.g. Alzheimer's, Huntington's and Parkinson's diseases) and therefore the experiments designed to dissect key trafficking pathways in prion toxicity will have relevance to these more common diseases. Thus despite being rooted in the basic mechanisms of prion disease, the research has the potential to influence academic research groups investigating other neurodegenerative diseases. In vivo models of AD, PD and HD require the expression of human mutant proteins, often with variable recapitulation of the human disease phenotype. In contrast, laboratory mice infected with prions genuinely succumb to prion disease, allowing us to identify which pathological mechanisms may be relevant to disease progression. Advances in understanding prion pathophysiology could therefore have major implications for other protein-misfolding disorders through the elucidation of common cellular mechanisms.

The stimulating research environment at the Institute of Neurology will train and deliver highly skilled researchers with the expertise and knowledge to investigate cellular mechanisms of pathology across a wide spectrum of neurodegenerative conditions. We recognise that there is an increasing demand to communicate research progress to the general public, in particular patients and their families. Through our public communication plans (see Pathways to Impact), we hope to provide reassurance that current research efforts are successfully dissecting complex disease aetiologies to identify new treatment options.

Publications

10 25 50
 
Description Molecular Characterization of FAN1 Variation in Huntington's disease
Amount £163,169 (GBP)
Organisation CHDI Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2017 
End 06/2018
 
Description Phenotypic Characterisation of normal and pathogenic human HTT-over-expressing NSC lines for Huntington's Disease.
Amount £6,620 (GBP)
Funding ID 097815/Z/11/B0 
Organisation Wellcome Trust 
Department Wellcome Trust Institutional Strategic Support Fund
Sector Charity/Non Profit
Country United Kingdom
Start 09/2014 
End 06/2015
 
Description Dr Maria Bjorkqvist 
Organisation Lund University
Country Sweden 
Sector Academic/University 
PI Contribution Intellectual contribution and reagents
Collaborator Contribution Intellectual contribution and reagents
Impact 18625748
Start Year 2006
 
Description Nico Dantuma Group 
Organisation Karolinska Institute
Department Department of Cell and Molecular Biology
Country Sweden 
Sector Academic/University 
PI Contribution Intellectual contribution and reagents
Collaborator Contribution Intellectual contribution and reagents
Impact Sarah has a paper with Nico Dantuma.  She says she has been collaborating with him from 2006: M Kristiansen, P Deriziotis, D Dimcheff, GS. Jackson, H Ovaa, H Naumann, F Leeuwen, V Benito, AR Clarke, NP Dantuma, JL Portis, J Collinge, SJ Tabrizi.  Disease associated prion protein oligomers inhibit the 26S proteasome. Molecular Cell. 2007 Apr 27;26(2):175-88. 
Start Year 2006
 
Description Professor Alfred Goldberg 
Organisation Harvard University
Department Harvard Medical School
Country United States 
Sector Academic/University 
PI Contribution Intellectual contribution and reagents
Collaborator Contribution Intellectual contribution and reagents
Impact Co-author of published paper in EMBO Journal, 2011 (Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition of substrate entry).
Start Year 2007
 
Description Professor Giampietro Schiavo 
Organisation Cancer Research UK
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Intellectual contribution and reagents.
Collaborator Contribution Intellectual contribution and reagents.
Impact Co-author of paper in Nature Communications, published in 2011 Goold R, Rabbanian S, Sutton L, Andre R, Arora P, Moonga J, Clarke AR, Schiavo G, Jat P, Collinge J, Tabrizi SJ. Rapid cell-surface prion protein conversion revealed using a novel cell system. Nature Communications. 2011;2:281. Goold R, McKinnon C, Rabbanian S, Collinge J, Schiavo G, Tabrizi SJ. Alternative fates of newly formed PrPSc upon prion conversion on the plasma membrane. Journal of Cell Science. 2013 Aug 15; 126(Pt 16):3552-62.
Start Year 2007
 
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 Michael Glickman 
Organisation Technion - Israel Institute of Technology
Department Faculty of Biology
Country Israel 
Sector Academic/University 
PI Contribution Intellectual contribution and reagents
Collaborator Contribution Intellectual contribution and reagents.
Impact Co-author of paper in EMBO Journal 2011 (Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition substrate entry).
Start Year 2007
 
Description AGM & family Conference, invited Guest Lecturer, Telford, Birmingham 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact Very well attended

Very useful for my research
Year(s) Of Engagement Activity 2012
 
Description 12th International Symposium on Neural Transplantation and Restoration (INTR12) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact 12th International Symposium on Neural Transplantation and Restoration (INTR12) held in Cardiff, UK

NO
Year(s) Of Engagement Activity 2013
URL http://www.nectar-eu.net/?q=node/28
 
Description 2013 World Congress on Huntington's Disease - WCHD - 13 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invitations and talks of this nature serve to enhance engagement with my research

Various
Year(s) Of Engagement Activity 2013
URL http://www.wchd2013.com/
 
Description 25th International Symposium on ALS/MND, Brussels 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented educational talk on HD to MNDA members
Year(s) Of Engagement Activity 2014
 
Description Article in the Lancet by Priya Shetty, Vol 379 June 2, 2012 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Articles of this nature serve to enhance engagement with my research

Various
Year(s) Of Engagement Activity 2012
URL http://www.thelancet.com
 
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 CAG Triplet Repeat Disorders, Tuscany, Italy 
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 on HD research to scientific peers and healthcare professionals
Year(s) Of Engagement Activity 2015
 
Description CHDI 10th Annual HD Therapeutics Conference 
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 on HD studies to researchers, healthcare practitioners and students.
Year(s) Of Engagement Activity 2015
 
Description Festival of Neuroscience - BNA meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Invitations and talks of this nature serve to enhance engagement with my research

Various
Year(s) Of Engagement Activity 2013
URL http://www.bna2013.com/207037
 
Description First Scientific Conference of International Progressive Multiple Sclerosis Collaborative 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Health professionals
Results and Impact First Scientific Conference of International Progressive Multiple Sclerosis Collaborative held in Milan in February 2013

No
Year(s) Of Engagement Activity 2013
URL http://www.msif.org/global-ms-news/msif-news/progressive-ms-meeting-in-milan.aspx
 
Description GSK Huntington's Disease Network Advisory meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Health professionals
Results and Impact very well attended

Good for sharing views
Year(s) Of Engagement Activity 2012
 
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 HSG 7th Annual HD Clinical Research Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invitations and talks of this nature serve to enhance engagement with my research

Various
Year(s) Of Engagement Activity 2013
URL http://www.huntington-study-group.org/Events/HSG2013/tabid/274/Default.aspx
 
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 Invitation to Guest Lecture at Edinburgh Clinical Neurosciences Academic Lecture Series, October 2012, Edinburgh. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Well attended

Very good
Year(s) Of Engagement Activity 2012
 
Description Key Advances in Neurodegenerative Disorders Meeting, Royal Society of Medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented education talk on HD to healthcare professionals
Year(s) Of Engagement Activity 2014
 
Description Leonard Wolfson UCL-BRU Biomarker Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact My talk was very well received

No aware of any
Year(s) Of Engagement Activity 2013
URL http://events.ucl.ac.uk/event/event:odi-h864377g-p7dq89/
 
Description MRC Centre for Neuromuscular Diseases Seminar Series 2015 
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 on therapeutic strategies in HD to students and professional practitioners alike. The talk generated lot's of interest and questions.
Year(s) Of Engagement Activity 2015
 
Description Marie-Curie Neuromodel Symposium, King's College, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Well attended

Good talks by other speakers
Year(s) Of Engagement Activity 2012
 
Description NIND Workshop on HD Biomarkers 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact NIND Workshop on HD Biomarkers held in Maryland, USA in February 2013

Various
Year(s) Of Engagement Activity 2013
URL http://www.ninds.nih.gov/
 
Description North Thames UK Dementia & Neurodegenerative Disease network 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact Well attended

Good for work
Year(s) Of Engagement Activity 2011
 
Description Oxford Neuroscience Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Invitations and talks of this nature serve to enhance engagement with my research

Well attended and my talk was very well received and appreciated
Year(s) Of Engagement Activity 2013
URL http://www.medsci.ox.ac.uk/events/4th-annual-oxford-neuroscience-symposium
 
Description Plenary Lecture - CIBERNED Annual Meeting co-organized by the Reina Sofia Foundation, Madrid 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Invitations and talks of this nature serve to enhance engagement with my research

Various
Year(s) Of Engagement Activity 2013
URL http://www.nadproject.eu/events-a-news.html
 
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 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 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 Scientific Seminar at the Department of cell and Molecular Biology (CMB) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Health professionals
Results and Impact Scientific Seminar at the Department of cell and Molecular Biology (CMB), Karolinska Institute, Stockholm held on 31st May 2013

No
Year(s) Of Engagement Activity 2013
URL http://ki.se/ki/jsp/polopoly.jsp?d=27084&a=25977&l=en
 
Description UCL Rare Disease Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Various
Year(s) Of Engagement Activity 2013
URL http://www.treat-nmd.eu/events/408/