The UK GENetic Frontotemporal dementia Initiative (UK GENFI)

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

Abstract

Frontotemporal dementia (FTD) is a common cause of young onset dementia. Its effect on people of working age with young families represents a major health and economic burden on society. The only known risk factors for FTD at present are genetic with abnormalities (mutations) in three genes accounting for the majority of familial FTD, called progranulin, tau and chromosome 9 open reading frame 72. There are now promising avenues for treatment of these disorders but we still do not know when drugs should be started or how we should measure the response to treatment. This study investigates people who have genetic (inherited) FTD, including both people who have developed symptoms and also their first-degree relatives who are at 50% risk of carrying the genetic mutation and therefore developing symptoms in the future. By studying individuals who carry the disease mutation and are thus destined to develop the disease we can understand the development from the very earliest changes, which would be the best time to start any treatment whilst the person remains well. A pilot phase of the study between 2011 and 2014 has created a common platform for studying genetic FTD and a standardized testing protocol. This study builds on the pilot phase by creating a UK-wide study of genetic FTD (at University College London, University of Cambridge, University of Manchester and the University of Oxford) over the next five years. It is expected that 200 participants will be seen, being assessed three times in total. Study participants will have psychology testing (tests of memory, language, behaviour etc.), brain imaging, blood tests and spinal fluid collection (by lumbar puncture) in order to investigate the patterns of change in these different tests at different stages of the disorder. The key outcomes of the study are to (1) improve understanding of how brain systems break down in genetic FTD and how this breakdown relates to the underlying behavioural and cognitive symptoms, (2) develop markers which help identify the disease at its earliest stage, and (3) develop markers that allow the progression of the disease to be tracked. The eventual aim will be to use these markers in future clinical trials of drugs in genetic FTD. The results of this project will also lead to improvement in the recognition and diagnosis of genetic FTD as well as provide improved information about prognosis for patients and members of their family.

Technical Summary

Frontotemporal dementia (FTD) is a common cause of young onset dementia, approximately equal in frequency to Alzheimer's disease in people below the age of 65. Its effect on people of working age with young families represents a major health and economic burden on society. The only known risk factors for FTD are genetic, and around a third of FTD is familial. There are currently no treatments that can delay the onset or prevent the progression of genetic FTD but there are now potential disease-modifying therapies in development. However, there are still no biomarkers of genetic FTD that can confidently predict when disease-modifying therapy should be initiated or how the response to it should be monitored. By studying participants who carry a mutation and are thus destined to develop the disease we can explore the entire disease pathway, using mutation negative first-degree relatives as controls. A pilot study has created a common methodological platform to study genetic FTD. This follow-on study aims to capitalize on the work of the pilot, extending both the platform and expertise generated to a UK-wide study of genetic FTD. Specifically, we will establish a UK-wide familial FTD cohort of 200 participants which will (1) lead to greater understanding of the biological underpinning of the cognitive and behavioural deficits seen in FTD; (2) permit large-scale cohesive and integrated longitudinal biomarker studies of familial FTD with the specific remit of informing clinical trial design; and (3) provide a "readiness" cohort of patients for disease-modifying drug trials. The experimental plan includes longitudinal clinical and neuropsychological assessments, neuroimaging and both blood and spinal fluid sampling, with the key outcomes including improved understanding regarding the selective vulnerability of the specific neural systems affected in FTD, robust biomarkers of disease onset and progression, and estimation of sample sizes required for trials.

Planned Impact

The outcomes of UK GENFI will lead to improvement in the recognition and diagnosis of genetic FTD as well as provide improved prognostic information for patients and members of their family in the first instance. UK GENFI will provide a platform for clinical trials in genetic FTD, likely to occur in the next five years: finding a disease-modifying therapy in this disorder will be hugely beneficial both for the patient and their families at risk of the disorder, as well as improving the nation's health and wealth by altering a disease process that affects people generally of working age. Based on the current understanding of the pathophysiology of the disease, it is probable that effective interventions for genetic FTD due to progranulin mutations will become available either by repurposing or from novel agents. Rapid evaluation will support the G8 declaration of a treatment for dementia by 2025. This would have significant UK political benefit building on the UK lead internationally in the G8 dementia summit.

The outcomes of UK GENFI in terms of biomarkers of disease onset and progression will feed into pharmaceutical industry-led studies, providing the knowledge required to identify the primary and secondary outcomes used in clinical trials and the timing of when the trials should take place.

Publications

10 25 50
 
Description Development of a methodological framework of presymptomatic clinical trials
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description Bluefield Project Grants - Developing a GENFI Biobank
Amount $148,222 (USD)
Organisation Bluefield Project 
Sector Charity/Non Profit
Country United States
Start 04/2016 
End 04/2018
 
Description JPND - Working Groups to Inform Cohort Studies in Neurodegenerative Disease Research
Amount € 34,178 (EUR)
Organisation EU Joint Programme - Neurodegenerative Disease Research (JPND) 
Sector Public
Country European Union (EU)
Start 10/2014 
End 05/2015
 
Description Novel fluid biomarkers of progranulin-associated FTD
Amount $219,999 (USD)
Organisation Bluefield Project 
Sector Charity/Non Profit
Country United States
Start 01/2019 
End 12/2020
 
Title GENFI XNAT database 
Description Database of biomarker data from the GENFI 1 and GENFI 2 projects (presymptomatic and early symptomatic genetic FTD). 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact 30 current analyses ongoing across multiple centres within GENFI. 
 
Description GENFI2 
Organisation August Pi i Sunyer Biomedical Research Institute
Department Hospital Clinic of Barcelona
Country Spain 
Sector Hospitals 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation Brescia Fatebenefratelli
Country Italy 
Sector Hospitals 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation Carlo Besta Neurological Institute
Country Italy 
Sector Public 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation Erasmus University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation Ludwig Maximilian University of Munich (LMU Munich)
Department University Clinic of Munich
Country Germany 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation McGill University
Country Canada 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation Pitié-Salpêtrière Hospital
Country France 
Sector Hospitals 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation UZ Leuven, Belgium
Country Belgium 
Sector Hospitals 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University Hospital Donostia
Country Spain 
Sector Hospitals 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University Hospital Tuebingen
Country Germany 
Sector Hospitals 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Brescia
Country Italy 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Coimbra
Country Portugal 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Florence
Country Italy 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Laval
Country Canada 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Lille
Country France 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Limoges
Country France 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Lisbon
Country Portugal 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Rouen
Country France 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Toronto
Country Canada 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation University of Ulm
Country Germany 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description GENFI2 
Organisation Western University
Country Canada 
Sector Academic/University 
PI Contribution I have led this multicentre international biomarkers study of genetic frontotemporal dementia, which has been co-ordinated from UCL.
Collaborator Contribution Partners are recruiting sites within the study.
Impact Publications - Lancet Neurology 2015; Annals of Clinical and Translational Neurology 2016; Presentations - International Conference on FTD 2014; International Conference on FTD 2016
Start Year 2015
 
Description Annual FTD support group seminar 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Seminar chaired by Jonathan Rohrer (supervisor) with talk by Elizabeth Gordon (PhD studentship) about her PhD work.
Year(s) Of Engagement Activity 2016
 
Description British Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Talk on young onset dementia and presymptomatic neurodegenerative disease highlighting the work of the GENFI project as part of the national British Science Festival - around 70 people attended with both a panel discussion and personal questions afterwards.
Year(s) Of Engagement Activity 2015
URL https://thelittleboxoffice.com/bsa/event/view/26635
 
Description Contribution to online learning module about dementia (MOOC) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Videoed talk and written information provided for an online learning tool about dementia - highlighting my research and work on GENFI project. Over 10,000 people currently signed up for course (official start March 2016).
Year(s) Of Engagement Activity 2016
URL https://www.futurelearn.com/courses/faces-of-dementia
 
Description FTD support group meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact ~70 people attended, mainly carers but also professionals, to hear about the latest research, with a question and answer session afterwards including discussion of patient involvement in future study design.
Year(s) Of Engagement Activity 2018
 
Description FTD talk website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I have set up and run a public engagement website dedicated to frontotemporal dementia (FTD talk) - it aims to provide information to the public about FTD, and particularly lay updates about research.
Year(s) Of Engagement Activity 2014,2015,2016,2017
URL http://www.ftdtalk.org
 
Description Familial FTD support group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Talk to around 100 people as part of the familial FTD support group annual day - discussion about GENFI and current research; questions and discussion about research from family members and those at risk of developing genetic FTD.
Year(s) Of Engagement Activity 2015
URL https://www.ucl.ac.uk/drc/support-groups/fFTD-support-group
 
Description Meet the researcher Youtube video 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Video made to inform people about research at UCL - interview about work on FTD.
Year(s) Of Engagement Activity 2014,2015,2016,2017
URL https://www.youtube.com/watch?v=8oMe4bgSHoY&feature=youtu.be
 
Description Pint of Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Around 100 people attended an event as part of the national Pint of Science Festival - discussion regarding young onset dementias and the work we are doing to find biomarkers and an evidence base for clinical trials - lots of questions and discussion afterwards and personal feedback from audience regarding how much they learned about the area.
Year(s) Of Engagement Activity 2015
 
Description Talk at FTD support group annual seminar 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Increased awareness of FTD research and the work we are doing to FTD support group consisting mainly of carers.
Year(s) Of Engagement Activity 2017
 
Description Talk to event for UK magistrates 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Talk on frontotemporal dementia to a UK magistrates event to inform them about forensic nature of symptomatology of FTD and how our research is exploring this further - long discussion afterwards about how this might inform the work of magistrates, particularly in considering dementia as a underlying problem with people who have been involved in crimes and therefore may change their practice.
Year(s) Of Engagement Activity 2015
 
Description The Science Museum - Science Lates - Dementia 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Organised and presented at a section of the Science Museum 'Science Lates' evening in April 2016. My section had 5 stands (manned by 10 of my team) each focused on different parts of clinical and imaging dementia research that represented our current research work, particularly focusing on young onset and genetic dementias. >4000 people attended the event. Many people said that their views and understanding about dementia changed as a result of visiting our section.
Year(s) Of Engagement Activity 2016