A Programme for ALS Care in Europe (ALS-CarE)
Lead Research Organisation:
King's College London
Department Name: Clinical Neuroscience
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that strikes in the prime of life. There are currently no effective disease modifying therapies for ALS and death usually occurs within 3 years of symptom onset. Management is palliative and is aimed at maximising quality of life and minimising the burden of disease. The complexity and rapidly progressive nature of ALS requires a responsive multidisciplinary care system that that is built on reliable disease staging and evidence based symptom management.
The purpose of ALS-CarE is to incorporate detailed clinical information drawn from population based sources into a responsive care programme. A standardised staging system will be validated, and quality of life and patient experiences will be measured and management optimised across disease stages from diagnosis to end of life. Health economic analysis will identify key differences in resource utilisation and will be useful for pharmaco-economic analyses of new therapeutics. The completed project will provide a user-friendly best practice framework for ALS that can be modified for management of other neurodegenerative diseases.
The purpose of ALS-CarE is to incorporate detailed clinical information drawn from population based sources into a responsive care programme. A standardised staging system will be validated, and quality of life and patient experiences will be measured and management optimised across disease stages from diagnosis to end of life. Health economic analysis will identify key differences in resource utilisation and will be useful for pharmaco-economic analyses of new therapeutics. The completed project will provide a user-friendly best practice framework for ALS that can be modified for management of other neurodegenerative diseases.
Planned Impact
For an Impact Summary relating to societal and economic impacts, please see the attached document "Pathways to Impact". This is a summary of the Academic Impact.
Although our partners come from six countries with very different health care systems and different cultures, all are members of a highly successful European ALS Consortium (ENCALS), with extensive existing collaborations in basic, translational and clinical aspects of ALS. The strength of this application, underpinned by our collective experience as key European ALS clinician scientists and healthcare researchers, gives us a unique opportunity to study and learn, both from the common elements and the differences between our systems and our services. The benefits of this proposal are further enhanced by existing support provided by the Health Research Board in Ireland to ALS-CarE Partner 1 (Dublin). Thanks to the work already undertaken within this three-year project, much of the infrastructure and methodological approaches needed for ALS-CarE are currently under development and will be readily available to the ALS-CarE consortium at the start of the project, thus expediting the research programme. The outcome will provide an expert-led evidence-based and user-friendly protocol for management of ALS in Europe that can also operate as a guide and
educational tool for non-specialist services and voluntary groups providing care for ALS. Moreover, on completion, the entire programme will be available for adaptation to other neurodegenerative conditions such as Alzheimer's Disease, Parkinson's Disease and frontotemporal dementia.
In order to establish a metric by which care can be measured from a health economic perspective, a strong focus will be placed on the components of the care matrix that are considered most useful by the users (patients and families). This will be achieved by integrating the outcome of a qualitative project currently funded by the Irish Health Research Board to examine user attitudes towards ALS care with the care matrix. As part of this process, patients and carers, (including international stakeholder organizations such as PatientslikeMe http://www.patientslikeme.com/research) will be provided with an opportunity to comment extensively on the usefulness of the care programme, yielding qualitative data that will be analysed to identify core themes that can be incorporated into existing and novel health economic tools.
ALS-CarE will seek regular advice through the Executive Board from eminent Health Services Researchers and Health Economists assembled in the Scientific Advisory Board (SAB) and stakeholders in the Stakeholder Platform. The SAB will provide expert advice on the content, quality of the deliverables, ethical issues, general philosophy and direction of the project, corrective measures in the content of the work if necessary and the dissemination and exploitation of project results. The SAB will be chaired by Dr. Brian Dickie from MNDA. The Consortium has obtained full commitment from ALS patient organisations from all participating countries.
Knowledge exchange within the consortium will be facilitated by yearly consortium meetings and an exchange program. Once every year a consortium meeting will be organised. During this meeting all the partners will discuss the project progress and will exchange other relevant knowledge in their field. For the last consortium meeting representatives of all national funding agencies and policy bodies will be invited to share the final results of the project. The ALSCarE consortium acknowledges that training of young researchers and mobility within the consortium will be beneficial for maximal knowledge transfer. Therefore, all consortium partners will exchange three of their (PhD) students and/or postdoctoral researchers for 2 - 4 months during the duration of this project. The aim will be to exchange knowledge of the main research techniques between different consortium members.
Although our partners come from six countries with very different health care systems and different cultures, all are members of a highly successful European ALS Consortium (ENCALS), with extensive existing collaborations in basic, translational and clinical aspects of ALS. The strength of this application, underpinned by our collective experience as key European ALS clinician scientists and healthcare researchers, gives us a unique opportunity to study and learn, both from the common elements and the differences between our systems and our services. The benefits of this proposal are further enhanced by existing support provided by the Health Research Board in Ireland to ALS-CarE Partner 1 (Dublin). Thanks to the work already undertaken within this three-year project, much of the infrastructure and methodological approaches needed for ALS-CarE are currently under development and will be readily available to the ALS-CarE consortium at the start of the project, thus expediting the research programme. The outcome will provide an expert-led evidence-based and user-friendly protocol for management of ALS in Europe that can also operate as a guide and
educational tool for non-specialist services and voluntary groups providing care for ALS. Moreover, on completion, the entire programme will be available for adaptation to other neurodegenerative conditions such as Alzheimer's Disease, Parkinson's Disease and frontotemporal dementia.
In order to establish a metric by which care can be measured from a health economic perspective, a strong focus will be placed on the components of the care matrix that are considered most useful by the users (patients and families). This will be achieved by integrating the outcome of a qualitative project currently funded by the Irish Health Research Board to examine user attitudes towards ALS care with the care matrix. As part of this process, patients and carers, (including international stakeholder organizations such as PatientslikeMe http://www.patientslikeme.com/research) will be provided with an opportunity to comment extensively on the usefulness of the care programme, yielding qualitative data that will be analysed to identify core themes that can be incorporated into existing and novel health economic tools.
ALS-CarE will seek regular advice through the Executive Board from eminent Health Services Researchers and Health Economists assembled in the Scientific Advisory Board (SAB) and stakeholders in the Stakeholder Platform. The SAB will provide expert advice on the content, quality of the deliverables, ethical issues, general philosophy and direction of the project, corrective measures in the content of the work if necessary and the dissemination and exploitation of project results. The SAB will be chaired by Dr. Brian Dickie from MNDA. The Consortium has obtained full commitment from ALS patient organisations from all participating countries.
Knowledge exchange within the consortium will be facilitated by yearly consortium meetings and an exchange program. Once every year a consortium meeting will be organised. During this meeting all the partners will discuss the project progress and will exchange other relevant knowledge in their field. For the last consortium meeting representatives of all national funding agencies and policy bodies will be invited to share the final results of the project. The ALSCarE consortium acknowledges that training of young researchers and mobility within the consortium will be beneficial for maximal knowledge transfer. Therefore, all consortium partners will exchange three of their (PhD) students and/or postdoctoral researchers for 2 - 4 months during the duration of this project. The aim will be to exchange knowledge of the main research techniques between different consortium members.
Organisations
- King's College London (Lead Research Organisation)
- University of Milan (Collaboration)
- University College London (Collaboration)
- Brighton and Sussex University Hospitals NHS Trust (Collaboration)
- National Institute of Health and Medical Research (INSERM) (Collaboration)
- University College Dublin (Collaboration)
- Karolinska Institute (Collaboration)
- Motor Neurone Disease Association (MND) (Collaboration)
- ENCALS (Collaboration)
- Université Catholique de Louvain (Collaboration)
- Trinity College Dublin (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- University of Turin (Collaboration)
- University of Sheffield (Collaboration)
- MND Scotland (Collaboration)
- Pitié-Salpêtrière Hospital (Collaboration)
- University Medical Center Utrecht (UMC) (Collaboration)
- University of Ulm (Collaboration)
- My Name'5 Doddie Foundation (Collaboration)
- UNIVERSITY OF EDINBURGH (Collaboration)
- University of Massachusetts (Collaboration)
- University of Leuven (Collaboration)
- Cantonal Hospital St. Gallen (Collaboration)
- EU Joint Programme - Neurodegenerative Disease Research (JPND) (Collaboration)
Publications
Agosta F
(2015)
The El Escorial criteria: strengths and weaknesses.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Al Khleifat A
(2019)
Telomere length is greater in ALS than in controls: a whole genome sequencing study.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Al Khleifat A
(2021)
Intuitive Staging Correlates With King's Clinical Stage.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Al-Chalabi A
(2021)
Preventing neurodegenerative disease.
in Brain : a journal of neurology
Al-Chalabi A
(2021)
Clinical staging in amyotrophic lateral sclerosis: analysis of Edaravone Study 19.
in Journal of neurology, neurosurgery, and psychiatry
Al-Chalabi A
(2014)
Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.
in The Lancet. Neurology
Al-Chalabi A
(2016)
Amyotrophic lateral sclerosis: moving towards a new classification system.
in The Lancet. Neurology
Al-Chalabi A
(2017)
Gene discovery in amyotrophic lateral sclerosis: implications for clinical management.
in Nature reviews. Neurology
Aragones JM
(2016)
Amyotrophic lateral sclerosis: A higher than expected incidence in people over 80 years of age.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Balendra R
(2022)
Comparison Of King's Clinical Staging In Multinational Amyotrophic Lateral Sclerosis Cohorts
in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Balendra R
(2014)
Estimating clinical stage of amyotrophic lateral sclerosis from the ALS Functional Rating Scale.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Balendra R
(2019)
A standard operating procedure for King's ALS clinical staging.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Balendra R
(2015)
Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials.
in Journal of neurology, neurosurgery, and psychiatry
Beer AM
(2015)
Intermediate length C9orf72 expansion in an ALS patient without classical C9orf72 neuropathology.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Benigni M
(2016)
Identification of miRNAs as Potential Biomarkers in Cerebrospinal Fluid from Amyotrophic Lateral Sclerosis Patients.
in Neuromolecular medicine
Bento-Abreu A
(2018)
Elongator subunit 3 (ELP3) modifies ALS through tRNA modification
in Human Molecular Genetics
Burke T
(2015)
Caregiver burden in amyotrophic lateral sclerosis: a cross-sectional investigation of predictors
in Journal of Neurology
Chen JA
(2018)
Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases.
in Molecular neurodegeneration
Chen Z
(2023)
The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases.
in Neurobiology of disease
Chen Z
(2017)
Proposed association between the hexanucleotide repeat of C9orf72 and opposability index of the thumb.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Chiò A
(2017)
Pain in amyotrophic lateral sclerosis.
in The Lancet. Neurology
Chiò A
(2016)
ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion.
in Neurobiology of aging
Cooper-Knock J
(2017)
Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants with Synergistic Effect on Clinical Phenotype.
in Frontiers in molecular neuroscience
Crockford C
(2018)
Measuring reliable change in cognition using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Crockford CJ
(2018)
ECAS A-B-C: alternate forms of the Edinburgh Cognitive and Behavioural ALS Screen.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Dolzhenko E
(2017)
Detection of long repeat expansions from PCR-free whole-genome sequence data.
in Genome research
Fang T
(2017)
Comparison of the King's and MiToS staging systems for ALS
in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Fogh I
(2016)
Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis.
in JAMA neurology
Gaastra B
(2016)
Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Gabel MC
(2020)
Evolution of white matter damage in amyotrophic lateral sclerosis.
in Annals of clinical and translational neurology
Galvin M
(2015)
Patient journey to a specialist amyotrophic lateral sclerosis multidisciplinary clinic: an exploratory study.
in BMC health services research
Garcia-Gancedo L
(2019)
Objectively Monitoring Amyotrophic Lateral Sclerosis Patient Symptoms During Clinical Trials With Sensors: Observational Study.
in JMIR mHealth and uHealth
Garson JA
(2019)
Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis.
in Acta neuropathologica communications
Giovannelli I
(2021)
Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2.
in Brain communications
Gold J
(2019)
Safety and tolerability of Triumeq in amyotrophic lateral sclerosis: the Lighthouse trial.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Gould RL
(2015)
Psychotherapy and pharmacotherapy interventions to reduce distress or improve well-being in people with amyotrophic lateral sclerosis: A systematic review.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Goutman SA
(2022)
Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis.
in The Lancet. Neurology
Goutman SA
(2022)
Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis.
in The Lancet. Neurology
Gowland A
(2019)
Predicting the future of ALS: the impact of demographic change and potential new treatments on the prevalence of ALS in the United Kingdom, 2020-2116.
in Amyotrophic lateral sclerosis & frontotemporal degeneration
Greenaway LP
(2015)
Accepting or declining non-invasive ventilation or gastrostomy in amyotrophic lateral sclerosis: patients' perspectives.
in Journal of neurology
Hardiman O
(2017)
The changing picture of amyotrophic lateral sclerosis: lessons from European registers.
in Journal of neurology, neurosurgery, and psychiatry
Hop PJ
(2022)
Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS.
in Science translational medicine
Hu J
(2021)
DGLinker: flexible knowledge-graph prediction of disease-gene associations
in Nucleic Acids Research
Hunt CK
(2021)
Does genetic anticipation occur in familial Alexander disease?
in Neurogenetics
Iacoangeli A
(2021)
SCFD1 expression quantitative trait loci in amyotrophic lateral sclerosis are differentially expressed.
in Brain communications
| Title | Livestream of talk |
| Description | Livestream video of a talk |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| Impact | The video has been widely viewed and remains available for patients and the public. |
| URL | https://www.youtube.com/watch?v=KRb1HWv08gQ |
| Title | PPI video for MND Association |
| Description | Video interview by MND Association for Twitter |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| Impact | Viewed many times by symposium attendees and the public |
| URL | https://twitter.com/mndassoc/status/1201961917117583362 |
| Title | YouTube educational video on ALS |
| Description | Educational video on ALS research available on YouTube |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2018 |
| Impact | Patient information and understanding about ALS and research |
| URL | https://www.youtube.com/watch?v=7KVSbwe7bHo |
| Description | An analysis of survival by symptom burden in ALS showed that disease burden confined to a neurological segment is associated with a worse prognosis than more diffuse disease. Quantitative and qualitative analyses of the factors influencing patient decision-making at different clinical stages emphasize the need for a precision medicine, individualised approach. Clinical staging has been applied retrospectively to two clinical trial datasets, showing that clinical stage has a role in clinical trial design. A combined staging system has been proposed incorporating both the Kings Clinical Staging System and the MiTOS Staging System to more meaningfully represent the illness throughout its complete course. Factors influencing decision making for gastrostomy and non-invasive ventilation show that person, care-giver and clinician-centred factors interact in a complex way requiring multi-professional input and a personalised approach to care. The patient's evaluation of quality of life, the desirability of prolonging life, and acceptance of the disease and its progression by both patient and caregiver were the most important factors in decision making about gastrostomy or non-invasive ventilation. A mapping review of international guidance on the management and care of ALS found that certain domains in ALS care, mainly disease-specific domains such as breathing and swallowing, are extensively addressed in the literature whereas other subjects, such as care coordination, receive little attention. This mapping review provides a scientific basis for targeting and developing the clinical content of a quality improvement intervention for the management of ALS. In an analysis of the clinical characteristics and palliative approaches in ALS patients a low ALSFRS-R, high incidence of ophthalmoplegia and extended ventilator dependency were found before withdrawing from long-term ventilation (WLTV). The key finding was that the presence or absence of ventilator-free tolerance determined the approach to the management of symptoms, the setting for immediate end-of-life care and the course of dying in WLTV. Clinical staging is now being included as an end-point in ALS clinical trials and in international consensus guidelines for ALS. |
| Exploitation Route | These findings can be used by pharmaceutical industry to inform clinical trial design, by multidisciplinary health care teams to inform care given to patients, how information should be given to patients, caregivers and health professionals, and palliative care and communication specialists in understanding communication needs and other interventions at end of life. In addition, new technologies for communication for example, need to be developed. These outcomes are the result of our findings in understanding phenotypic presentations and their relationship to the disease journey, our findings on clinical staging, our findings on understanding decision making factors, and our findings on end of life changes and interventions. |
| Sectors | Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | The findings from this study allowed me to provide evidence to government over two years, influencing government policy and resulting in a pledge from the Secretary of State for Health, Sajid Javid, and the Secretary of State for Business, Kwasi Kwarteng, to fund a national coordinated programme of work for £50m over 5 years to accelerate the search for a cure for MND. We developed an ALS staging system which is being refined within the ALS-CarE programme and applied within the STRENGTH programme. ALS Staging systems have been used for harmonised clinical trials training across Europe, for analysis of the timing of cognitive change in ALS, and for consultancy and advisory work for multiple pharmaceutical companies. The staging systems are now included as endpoints in commercial clinical trials and in international consensus ALS guidelines. |
| First Year Of Impact | 2021 |
| Sector | Healthcare,Government, Democracy and Justice,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal,Economic,Policy & public services |
| Description | Advisory Committee for large pharmaceutical company |
| Geographic Reach | North America |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | A new drug for ALS is now available, an outcome influenced by this advisory panel. The drug influences quality of life. |
| Description | Advisory committee for a small pharmaceutical company |
| Geographic Reach | Europe |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Description | Airlie House ALS Clinical Trials Guidelines |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | This was an international consultation on best practice for clinical trials in ALS, facilitated through a Delphi process. The best practice guidelines are still in review but almost finalized. |
| Description | Association of British Neurologists Genetics Advisory Committee |
| Geographic Reach | National |
| Policy Influence Type | Membership of a guideline committee |
| Description | COVID guidance for patients |
| Geographic Reach | National |
| Policy Influence Type | Membership of a guideline committee |
| Impact | Worked with the Motor Neurone Disease Association to provide national advice to patients with MND during the COVID pandemic, improving quality of life and reducing risk of infectiob, hospitalization and death. |
| URL | https://www.mndassociation.org/about-mnd/coronavirus-and-mnd/ |
| Description | COVID guidelines for shielding |
| Geographic Reach | National |
| Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
| Impact | Advice given to the Chief Medical Officer (via the DCMO's office) regarding shielding for people with motor neuron disease. As a result, communications were put in place through the Royal College of General Practitioners and training made available to GPs. |
| Guideline Title | Guideline on clinical investigation of medicinal products for the treatment of amyotrophic lateral sclerosis (ALS) |
| Description | Citation in European Medicines Agency (EMA) Guidelines |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | Clinical staging is being used as an endpoint for clinical trials improving understanding of the timing of treatment impact, health economics impact of treatment, and making trials more efficient. |
| URL | https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicin... |
| Guideline Title | Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry |
| Description | Citation of ALS clinical staging in FDA guidelines for clinical trials |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | Recommendation for commercial and academic-led trials in ALS to consider disease stage for inclusion and outcome |
| URL | https://www.regulations.gov/document?D=FDA-2013-N-0035-0973 |
| Guideline Title | A proposal for new diagnostic criteria for ALS |
| Description | Gold Coast Criteria for the Diagnosis of ALS |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | These are new diagnostic criteria for ALS and improve the way in which the diagnosis is given, simplify the route to making a diagnosis (therefore speeding it), improve access to clinical trials and clarify the diagnosis for patients, improving understanding. |
| URL | https://www.sciencedirect.com/science/article/pii/S1388245720301383?via%3Dihub |
| Description | Guidance on prevention strategies for ALS |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Membership of a guideline committee |
| Description | Guidelines for pain management in MND/ALS |
| Geographic Reach | National |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | As a result of a study of pain in MND/ALS, we have published advice for patients and for health care professionals for the management of pain, and this has been adopted by the patient organisation, the Motor Neurone Disease Association |
| URL | https://www.mndassociation.org/forprofessionals/mndmanagement/pain/ |
| Description | Influencing government policy on Continuing HealthCare (CHC) |
| Geographic Reach | National |
| Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
| Guideline Title | Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials |
| Description | King's Clinical ALS Staging |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | The clinical staging system is now recommended for ALS clinical trials, and is required by the FDA for future trials. |
| Guideline Title | Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials |
| Description | King's clinical staging - in consensus guidelines for clinical trials in ALS |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| URL | https://n.neurology.org/content/neurology/early/2019/03/08/WNL.0000000000007242.full.pdf |
| Description | Staging for clinical practice and clinical trials |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The influence is a clinical staging system for ALS. This has been used by 12 European countries, all trained in assessment and certified. It has also been used for research and clinical practice in at least one US ALS clinic. |
| Description | Standard operating procedure for King's ALS clinical staging |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | King's ALS clinical staging is now widely used in clinical practice and in clinical trials and other clinical research. This standard operating procedure ensures practice is uniform worldwide. |
| URL | https://www.ncbi.nlm.nih.gov/pubmed/30773950 |
| Description | Standardised method for application of ALSFRS-R |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The ALSFRS-R is a rating scale for assessing function in ALS. The influence is a standardised method for application of the ALSFRS-R, trained and certified across 12 European countries, ensuring standardised assessment and harmonised outcomes. |
| Description | Timing of Riluzole use by clinical stage of ALS |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | We showed that Riluzole extends the last stages of life with ALS. It has since also been shown that it extends the very early stages too by replicating our methods applied to a different dataset. These findings have impact on the advice given to patients, and mean that RIluzole should be started early, but also its use in late stage needs discussion with the patient, since it will simply extend life at a stage where health related quality of life is poor. |
| URL | https://www.ncbi.nlm.nih.gov/pubmed/29525492 |
| Description | UK MND Translational Research Institute |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| Impact | Multiple institutions nationally have worked with four charities, several patients, and industry partners to produce a vision for motor neuron disease research nationally. The government agreed to fund our vision in full. A pilot proposal has been submitted and is in peer review. This brought together 6 institutions, 6 funders and 3 industry partners to accelerate research into a cure for motor neuron disease. |
| URL | https://www.mndassociation.org/get-involved/campaigning/take-action/united-to-end-mnd/ |
| Description | JPND ALS-CarE |
| Amount | £78,400 (GBP) |
| Organisation | JPND Research |
| Sector | Academic/University |
| Country | Global |
| Start | 02/2014 |
| End | 01/2017 |
| Description | MNDA Project Grant (The UK National MND Registry) |
| Amount | £277,101 (GBP) |
| Organisation | Motor Neurone Disease Association (MND) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2014 |
| End | 09/2019 |
| Description | NIHR Healthcare |
| Amount | £9,237 (GBP) |
| Organisation | National Institute for Health Research |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2014 |
| End | 09/2017 |
| Description | Programme Grant (MIROCALS) |
| Amount | £387,723 (GBP) |
| Funding ID | 633413 |
| Organisation | European Commission |
| Department | Horizon 2020 |
| Sector | Public |
| Country | European Union (EU) |
| Start | 09/2015 |
| End | 08/2019 |
| Description | Research Grant (ALSoD) |
| Amount | £102,469 (GBP) |
| Organisation | The ALS Association |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 02/2017 |
| End | 01/2020 |
| Description | Research Grant (ALSoD) |
| Amount | £40,000 (GBP) |
| Organisation | Motor Neurone Disease Association (MND) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2017 |
| End | 01/2020 |
| Description | Research Grant (ATXN2 penetrance) |
| Amount | £134,207 (GBP) |
| Organisation | Motor Neurone Disease Association (MND) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 11/2015 |
| End | 08/2019 |
| Description | Research Grant (Bioinformatics) |
| Amount | £171,749 (GBP) |
| Organisation | Motor Neurone Disease Association (MND) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2014 |
| End | 09/2017 |
| Description | Research Grant (COMMEND) |
| Amount | £1,373,735 (GBP) |
| Organisation | National Institute for Health Research |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2012 |
| End | 05/2022 |
| Description | Research Grant (JPND BRAIN-MEND) |
| Amount | £2,044,052 (GBP) |
| Funding ID | MR/R024804/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2018 |
| End | 01/2021 |
| Description | Research Grant Fellowship |
| Amount | £265,000 (GBP) |
| Organisation | Motor Neurone Disease Association (MND) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2016 |
| End | 02/2019 |
| Description | Research Grant Studentship |
| Amount | £95,574 (GBP) |
| Organisation | Motor Neurone Disease Association (MND) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2018 |
| End | 06/2021 |
| Title | ENCALS Survival Model for ALS |
| Description | This mathematical tool allows a personalized survival prediction for patients. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | The tool allows a personalized survival prediction for any individual patient. This is used in clinic by neurologists to counsel patients, but is particularly useful for the design of clinical trials, and is now being used as an inclusion criterion in trials. |
| URL | http://encalssurvivalmodel.org/ |
| Title | King's Clinical Staging for ALS |
| Description | King's Clinical Staging is a system for describing ALS disease stage using simple clinical parameters. It was first published in 2012, but as a result of the award ALS-CarE, has been developed further, validated, used by multiple other research groups, and implemented into clinical practice internationally. It has also been used and developed for analysis of genetic outcomes in the award STRENGTH. |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | 1. Multiple other research groups have used this method for analysis (eg Association between estimated total daily energy expenditure and stage of amyotrophic lateral sclerosis. Lee J et al. Nutrition. 2017 Jan;33:181-186. PMID: 27544003; Amyotrophic lateral sclerosis: a comparison of two staging systems in a population-based study. Ferraro D et al. Eur J Neurol. 2016 Sep;23(9):1426-32. PMID: 27238551; Neuropsychological assessment in different King's clinical stages of amyotrophic lateral sclerosis. Trojsi F et al. Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(3-4):228-35. PMID: 26905940 and others). 2. Several pharmaceutical companies have started to use the method as an outcome measure in clinical trials for ALS 3. An academic led clinical trial is using ALS staging as an outcome measure 4. ALS Staging is now included as a formal outcome measure in international consensus guidelines from the World Federation of Neurology (see section 3 in URL below) |
| URL | https://www.rarediseasesnetwork.org/cms/Portals/5/Final%20Draft%20of%20ALS%20CT%20Guidelines%20for%2... |
| Title | Latent class cluster analysis |
| Description | Patients are stratified into clinical subgroups based on latent class cluster analysis of variables ascertained at first clinic visit. This strongly predicts survival, may predict genetic subgroups and can be replicated in multiple populations |
| Type Of Material | Model of mechanisms or symptoms - human |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | This method is now used across European ALS research groups to stratify patients for research, and is being studied in two different programme grants as a stratification method. |
| Title | Multistage model of ALS |
| Description | We have applied a model derived from the cancer field to neurodegeneration. We have shown that ALS is a 6-step process rather than a dose-dependent process. |
| Type Of Material | Model of mechanisms or symptoms - human |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | This represents a large change in the prevailing disease model and will allow new approaches for identification of risk factors and prevention strategies. |
| URL | http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(14)70219-4/fulltext |
| Title | Standard Operating Procedure for King's ALS Clinical Staging |
| Description | Clinical staging method for people with ALS. The King's system is now widely used internationally in clinic, research and clinical trials. |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | Clinical trial design now incorporates King's staging to understand the timing of treatment benefit, for analysis as an outcome measure, and for health economics analysis. |
| URL | https://www.ncbi.nlm.nih.gov/pubmed/30773950 |
| Title | ALSoD |
| Description | The ALS Online Database is a genetic database showing all ALS related genetic variations with their evidence and various tools for understanding phenotype, penetrance, publications and credibility. |
| Type Of Material | Database/Collection of data |
| Provided To Others? | Yes |
| Impact | Currently, data from this database is being used to inform commercial gene therapy studies in ALS. It is also widely accessed internationally and therefore used in multiple research projects. |
| URL | http://www.alsod.ac.uk |
| Title | Latent Class Cluster Analyses (LCCA) |
| Description | A latent class cluster analyses is a latent variable model where the latent variable is a categorical variable with k possible latent classes and the observed items are either categorical or continuous. It is used to classify ALS patients on the basis of the described variables into symptom clusters. In our study the cluster solution needs to be controlled for country. This is done by multi-group latent cluster modelling, which compares the structure of measurement models across groups (in this case: countries) and allows to control for differences between countries. It is similar to factorial invariance assessment in factor analyses. Multi-group latent class cluster analyses were performed by including "country" as a categorical predictor variable of the latent class in the model (Kuha 2013). |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | For each cluster solution the measurement model equivalence with latent cluster probabilities varying between countries (proportion of clusters can differ between countries) but the same measurement model between countries (the relationship between items and latent variables is the same between countries) fits data best. After selecting the specification of the multi-group latent variable model the number of classes was determined by comparing goodness of fit measures. Figure 2 shows the information criteria (smaller is better model) for the different number of clusters. It can be seen that information criteria decrease with increasing number of clusters but decrease slows down after 4 to 5 clusters. After 5 clusters, clusters split in smaller ones or new clusters become extremely small. We therefore decided to select the 5 cluster solution which is similar to the previous studies. The entropy of the selected model was very good (0.95). |
| Title | National MND Register |
| Description | A national population register capturing every case of ALS in the UK with clinical information |
| Type Of Material | Database/Collection of data |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | The database will be used as the basis of a funded research programme, AMBROSIA, designed to identify biomarkers for ALS |
| Title | Project MinE databrowser |
| Description | Summary statistics and output from the Project MinE whole genome sequencing consortium |
| Type Of Material | Database/Collection of data |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | Increased ability for researchers to identify ALS genes or interpret their own findings. Increased collaboration. |
| URL | http://databrowser.projectmine.com/ |
| Title | Survival prediction model for ALS |
| Description | A comprehensive survival prediction tool for ALS |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | Use of the model by pharmaceutical company analyzing clinical trial data |
| URL | http://encalssurvivalmodel.org/ |
| Description | ALS-CarE |
| Organisation | Trinity College Dublin |
| Country | Ireland |
| Sector | Academic/University |
| PI Contribution | Epidemiology, cognitive and phenotyping data |
| Collaborator Contribution | Epidemiology, cognitive and phenotyping expertise, as well as qualitative expertise |
| Impact | See form under publications. Multidisciplinary including health services research, environmental studies and phenotyping. |
| Start Year | 2014 |
| Description | BRAIN-MEND |
| Organisation | EU Joint Programme - Neurodegenerative Disease Research (JPND) |
| Country | European Union (EU) |
| Sector | Public |
| PI Contribution | Coordinator. Samples, expertise, data, infrastructure |
| Collaborator Contribution | Samples, expertise, data, infrastructure |
| Impact | None yet |
| Start Year | 2018 |
| Description | MIROCALS consortium |
| Organisation | Brighton and Sussex University Hospitals NHS Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We have helped design the project, recruited patients to a clinical trial, and we are now performing whole genome sequencing on the samples to determine responder genotypes |
| Collaborator Contribution | Setup of the study, recruitment of patients, basic science research in RNA and immunology |
| Impact | Publications: https://www.tandfonline.com/doi/full/10.1080/21678421.2018.1562553 https://www.tandfonline.com/doi/full/10.1080/21678421.2017.1349151 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558284/ https://link.springer.com/article/10.1186/s40478-019-0724-4 https://eprints.soton.ac.uk/430197/1/Telomere_length_is_greater_in_ALS_than_in_controls_a_whole_genome_sequencing_study.pdf |
| Start Year | 2015 |
| Description | MIROCALS consortium |
| Organisation | Pitié-Salpêtrière Hospital |
| Country | France |
| Sector | Hospitals |
| PI Contribution | We have helped design the project, recruited patients to a clinical trial, and we are now performing whole genome sequencing on the samples to determine responder genotypes |
| Collaborator Contribution | Setup of the study, recruitment of patients, basic science research in RNA and immunology |
| Impact | Publications: https://www.tandfonline.com/doi/full/10.1080/21678421.2018.1562553 https://www.tandfonline.com/doi/full/10.1080/21678421.2017.1349151 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558284/ https://link.springer.com/article/10.1186/s40478-019-0724-4 https://eprints.soton.ac.uk/430197/1/Telomere_length_is_greater_in_ALS_than_in_controls_a_whole_genome_sequencing_study.pdf |
| Start Year | 2015 |
| Description | Precision ALS |
| Organisation | University College Dublin |
| Country | Ireland |
| Sector | Academic/University |
| PI Contribution | We are contributing clinical data from a population register of ALS |
| Collaborator Contribution | A large data handling and storage infrastructure, able to link multiple forms of data internationally |
| Impact | None yet |
| Start Year | 2022 |
| Description | Project MinE |
| Organisation | Trinity College Dublin |
| Department | Neurology |
| Country | Ireland |
| Sector | Academic/University |
| PI Contribution | This is an international whole genome sequencing consortium possible because of the infrastructure derived from the MRC/JPND programme STRENGTH - we have contributed 2000 ALS and control samples as well as funding and a template for other teams to obtain funding |
| Collaborator Contribution | The partners have contributed whole genome sequences and negotiated with us for infrastructure. See http://www.projectmine.com |
| Impact | Various genetics papers listed under STRENGTH programme |
| Start Year | 2014 |
| Description | Project MinE |
| Organisation | University Medical Center Utrecht (UMC) |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | This is an international whole genome sequencing consortium possible because of the infrastructure derived from the MRC/JPND programme STRENGTH - we have contributed 2000 ALS and control samples as well as funding and a template for other teams to obtain funding |
| Collaborator Contribution | The partners have contributed whole genome sequences and negotiated with us for infrastructure. See http://www.projectmine.com |
| Impact | Various genetics papers listed under STRENGTH programme |
| Start Year | 2014 |
| Description | Project MinE |
| Organisation | University of Massachusetts |
| Department | University of Massachusetts Medical School |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | This is an international whole genome sequencing consortium possible because of the infrastructure derived from the MRC/JPND programme STRENGTH - we have contributed 2000 ALS and control samples as well as funding and a template for other teams to obtain funding |
| Collaborator Contribution | The partners have contributed whole genome sequences and negotiated with us for infrastructure. See http://www.projectmine.com |
| Impact | Various genetics papers listed under STRENGTH programme |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | Cantonal Hospital St. Gallen |
| Country | Switzerland |
| Sector | Hospitals |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | Catholic University of Louvain |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | Karolinska Institute |
| Country | Sweden |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | National Institute of Health and Medical Research (INSERM) |
| Department | Nimes (INSERM) |
| Country | France |
| Sector | Public |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | Trinity College Dublin |
| Country | Ireland |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | University Medical Center Utrecht (UMC) |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | University of Leuven |
| Department | laboratory for cognitive neurology |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | University of Milan |
| Country | Italy |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | University of Sheffield |
| Department | Sheffield Institute for Translational Neuroscience (SITraN) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | University of Turin |
| Country | Italy |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | STRENGTH |
| Organisation | University of Ulm |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | This is a JPND Consortium for which I am coordinator |
| Collaborator Contribution | We provide genetics, statistical, bioinformatics, epigenetics, epidemiology and complex disease expertise. |
| Impact | Please see form publications. The collaboration is multidisciplinary including genetics, epidemiology, epigenetics, statistics and bioinformatics |
| Start Year | 2014 |
| Description | TRICALS |
| Organisation | ENCALS |
| Country | Netherlands |
| Sector | Private |
| PI Contribution | Expertise in setting up a Europe wide clinical trials consortium. Training of staff in King's clinical ALS staging |
| Collaborator Contribution | Access to data from large pan-European population ALS registers. Expertise in setting up a clinical trials consortium |
| Impact | Training programme for TRICALS at https://www.encals.eu/meetings/tricals-workshop/ |
| Start Year | 2016 |
| Description | UK MND Research Institute |
| Organisation | MND Scotland |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | I am the scientific lead for a national programme for MND research. The collaboration was to ask government for £50M for MND research over 5 years, with matched industry and charity funding. A government announcement was made confirming we were successful in September. |
| Collaborator Contribution | This has been a team effort, with fortnightly meetings for two years. |
| Impact | AS a result of this campaign, public knowledge of MND is far greater than before. We achieved a parliamentary debate, repeated national news coverage (which continues), policy change from government, policy change from the Welsh Senedd in progress, meetings with government ministers and advisers, and a pledge of funding from government. |
| Start Year | 2020 |
| Description | UK MND Research Institute |
| Organisation | Motor Neurone Disease Association (MND) |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | I am the scientific lead for a national programme for MND research. The collaboration was to ask government for £50M for MND research over 5 years, with matched industry and charity funding. A government announcement was made confirming we were successful in September. |
| Collaborator Contribution | This has been a team effort, with fortnightly meetings for two years. |
| Impact | AS a result of this campaign, public knowledge of MND is far greater than before. We achieved a parliamentary debate, repeated national news coverage (which continues), policy change from government, policy change from the Welsh Senedd in progress, meetings with government ministers and advisers, and a pledge of funding from government. |
| Start Year | 2020 |
| Description | UK MND Research Institute |
| Organisation | My Name'5 Doddie Foundation |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | I am the scientific lead for a national programme for MND research. The collaboration was to ask government for £50M for MND research over 5 years, with matched industry and charity funding. A government announcement was made confirming we were successful in September. |
| Collaborator Contribution | This has been a team effort, with fortnightly meetings for two years. |
| Impact | AS a result of this campaign, public knowledge of MND is far greater than before. We achieved a parliamentary debate, repeated national news coverage (which continues), policy change from government, policy change from the Welsh Senedd in progress, meetings with government ministers and advisers, and a pledge of funding from government. |
| Start Year | 2020 |
| Description | UK MND Research Institute |
| Organisation | University College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am the scientific lead for a national programme for MND research. The collaboration was to ask government for £50M for MND research over 5 years, with matched industry and charity funding. A government announcement was made confirming we were successful in September. |
| Collaborator Contribution | This has been a team effort, with fortnightly meetings for two years. |
| Impact | AS a result of this campaign, public knowledge of MND is far greater than before. We achieved a parliamentary debate, repeated national news coverage (which continues), policy change from government, policy change from the Welsh Senedd in progress, meetings with government ministers and advisers, and a pledge of funding from government. |
| Start Year | 2020 |
| Description | UK MND Research Institute |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am the scientific lead for a national programme for MND research. The collaboration was to ask government for £50M for MND research over 5 years, with matched industry and charity funding. A government announcement was made confirming we were successful in September. |
| Collaborator Contribution | This has been a team effort, with fortnightly meetings for two years. |
| Impact | AS a result of this campaign, public knowledge of MND is far greater than before. We achieved a parliamentary debate, repeated national news coverage (which continues), policy change from government, policy change from the Welsh Senedd in progress, meetings with government ministers and advisers, and a pledge of funding from government. |
| Start Year | 2020 |
| Description | UK MND Research Institute |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am the scientific lead for a national programme for MND research. The collaboration was to ask government for £50M for MND research over 5 years, with matched industry and charity funding. A government announcement was made confirming we were successful in September. |
| Collaborator Contribution | This has been a team effort, with fortnightly meetings for two years. |
| Impact | AS a result of this campaign, public knowledge of MND is far greater than before. We achieved a parliamentary debate, repeated national news coverage (which continues), policy change from government, policy change from the Welsh Senedd in progress, meetings with government ministers and advisers, and a pledge of funding from government. |
| Start Year | 2020 |
| Description | UK MND Research Institute |
| Organisation | University of Sheffield |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am the scientific lead for a national programme for MND research. The collaboration was to ask government for £50M for MND research over 5 years, with matched industry and charity funding. A government announcement was made confirming we were successful in September. |
| Collaborator Contribution | This has been a team effort, with fortnightly meetings for two years. |
| Impact | AS a result of this campaign, public knowledge of MND is far greater than before. We achieved a parliamentary debate, repeated national news coverage (which continues), policy change from government, policy change from the Welsh Senedd in progress, meetings with government ministers and advisers, and a pledge of funding from government. |
| Start Year | 2020 |
| Description | United2EndMND Research Group |
| Organisation | University College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am the scientific lead for a national campaign for funding MND Research over 5 years through a national programme of research. With colleagues, I have successfully lobbied for funding. We have developed a scientific vision for the programme. An initial pilot scheme using £4.25M is described here. |
| Collaborator Contribution | Colleagues have helped develop the vision and written the programme of work, leading various work packages. |
| Impact | None yet |
| Start Year | 2021 |
| Description | United2EndMND Research Group |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am the scientific lead for a national campaign for funding MND Research over 5 years through a national programme of research. With colleagues, I have successfully lobbied for funding. We have developed a scientific vision for the programme. An initial pilot scheme using £4.25M is described here. |
| Collaborator Contribution | Colleagues have helped develop the vision and written the programme of work, leading various work packages. |
| Impact | None yet |
| Start Year | 2021 |
| Description | United2EndMND Research Group |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am the scientific lead for a national campaign for funding MND Research over 5 years through a national programme of research. With colleagues, I have successfully lobbied for funding. We have developed a scientific vision for the programme. An initial pilot scheme using £4.25M is described here. |
| Collaborator Contribution | Colleagues have helped develop the vision and written the programme of work, leading various work packages. |
| Impact | None yet |
| Start Year | 2021 |
| Description | United2EndMND Research Group |
| Organisation | University of Sheffield |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am the scientific lead for a national campaign for funding MND Research over 5 years through a national programme of research. With colleagues, I have successfully lobbied for funding. We have developed a scientific vision for the programme. An initial pilot scheme using £4.25M is described here. |
| Collaborator Contribution | Colleagues have helped develop the vision and written the programme of work, leading various work packages. |
| Impact | None yet |
| Start Year | 2021 |
| Title | Lighthouse Trial |
| Description | Phase 2 trial of Triumeq in ALS now complete and published. Seeking Phase 3 start. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2019 |
| Development Status | Actively seeking support |
| Clinical Trial? | Yes |
| Impact | Increased collaboration internationally on ALS clinical trials |
| URL | https://www.tandfonline.com/doi/full/10.1080/21678421.2019.1632899 |
| Title | Lithium PRELUDE trial |
| Description | We have shown that Lithium carbonate, while ineffective in ALS as a whole, is effective in people with a poor prognosis genetic variant in the UNC13A gene (homozygosity for the CC genotype). We are now seeking funding for a trial of lithium in patients with ALS who carry this poor prognosis variant. This will be a precision medicine approach in ALS. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2019 |
| Development Status | Actively seeking support |
| Impact | The initial findings have been published, and if the trial confirms the analysis, this will become a new treatment for ALS. |
| URL | https://www.ncbi.nlm.nih.gov/pubmed/28978660 |
| Title | MIROCALS |
| Description | A clinical trial of low-dose interleukin-2 for amyotrophic lateral sclerosis, currently in a Phase 2 clinical trial, funded by Horizon 2020 and the MND Association |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2015 |
| Development Status | Under active development/distribution |
| Impact | The trial includes an assessment of Riluzole therapy, the first of its kind |
| URL | http://www.mirocals.eu/en/ |
| Title | Survival model for ALS |
| Description | A tool for predicting survival in ALS |
| Type Of Technology | Webtool/Application |
| Year Produced | 2018 |
| Impact | Use of the prediction tool for analysis of clinical trial phase 2 data |
| URL | http://www.encalssurvivalmodel.org |
| Title | Unique global ID for ALS research |
| Description | We have developed a tool to convert clinical information into a unique global ID using SHA2 encryption. The method allows sharing of IDs between research groups to identify duplicates or match participants, without breaking anonymisation. It uses a salt to protect against brute force breaking of anonymity. |
| Type Of Technology | Webtool/Application |
| Year Produced | 2016 |
| Impact | This method is now being used across Europe in several studies including ALS-CarE, STRENGTH, the UK National MND Register and others, including retrospective application of the system to previous studies such as LiCALS and the UK MND DNA Bank, allowing further analyses to take place. |
| Description | 25th International Symposium on ALS/MND (Brussels) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | At the International Symposium on ALS/MND this year over 800 people came together to hear the latest research findings. The 26th annual event was a truly international affair, with scientists and health professionals from over 30 countries attending. The clinical trials session was a great example of this and featured presentations from Japanese, American and South Korean researchers. Everyone who attended the Symposium was encouraged by the biomedical and care research that was discussed, including interesting conversations on how we classify MND, and how MND originates and spreads from one part of the body to another. There was a particularly thought provoking session on the way neurologists communicate a diagnosis of MND, put very eloquently by Juliet Jacobsen as 'delivering the horrible information in a hopeful way'. |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.mndassociation.org/research/international-symposium/ |
| Description | 26th International Symposium on ALS/MND (Orlando) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The symposium is the largest medical and scientific conference specific to MND and is the premier event in the MND research calendar for discussion on the latest advances in research and clinical management. Each year, the symposium attracts over 800 delegates, representing the energy and dynamism of the global MND research community. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://www.encals.eu/past-meeting/encals-satellite-meeting-2015-orlando/ |
| Description | Addressing the All Party Parliamentary Group on MND |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Presentation to the APPG on MND regarding our campaign for a step change in the quantity and nature of research funding for MND. Presented on 3 occasions. Attended by multiple politicians on each occasion. As a result, parliamentary questions were asked on our behalf and government policy was changed. |
| Year(s) Of Engagement Activity | 2021,2022 |
| URL | https://www.mndassociation.org/get-involved/campaigning/take-action/united-to-end-mnd/ |
| Description | Amsterdam City Swim 2015 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Professor Ammar Al-Chalabi took part in the 2 km Amsterdam City Swim 2015 which took place on Sunday, 06 September in Amsterdam's Central Canal and successfully raised £540.00 for the Motor Neurone Disease Association. |
| Year(s) Of Engagement Activity | 2015 |
| URL | https://www.justgiving.com/AmmarAl-Chalabi |
| Description | Ask the Experts Panel at International Symposium |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | A live audience and online audience watched a presentation and then asked questions on ALS research |
| Year(s) Of Engagement Activity | 2015 |
| URL | https://www.youtube.com/watch?v=U98WU4Zzu8s |
| Description | ENCALS meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | About 50 people attended the European Network for the Cure of ALS satellite meeting at the International ALS Symposium in Dublin. There was significant discussion around clinical staging, multistep models, and genetics of ALS |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.encals.eu/wp-content/uploads/2016/09/20161206-program-ENCALS-satellite-Dublin.pdf |
| Description | ENCALS meeting 2014 Leuven |
| 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 | ENCALS is a network of ALS centres in Europe. It was established to help develop the standards of clinical and biomedical MND research across Europe and create a more collaborative environment for researchers, industry, funding agencies and Patient Associations. However, the meeting had a very transatlantic flavour, thanks to the participation of several of the leading researchers from North America. With around 40 speakers, as well as numerous poster presentations, there is too much to cover in a few hundred words, so I'll focus on just a few of the key themes that were covered. |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.encals.eu/past-meeting/encals-meeting-2014-leuven/ |
| Description | ENCALS meeting 2015 Dublin |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | The ENCALS meeting is an important forum for the European MND community. The aim of the meeting is to encourage younger researchers to present their data, and to meet and interact with more established members of the community. The program highlighted state-of the-art science and clinical practice in the field of ALS. The focus was on Genes and Genomics, Cognition, C9orf72 and Novel Therapeutics, Imaging, TDP: RNA Metabolism and Disease Pathogenesis, Disease Models and Pathogenesis and Novel Biomarkers. Top international speakers provided cutting edge overviews. The meeting in Dublin was a great success with over 30 oral presentations and 80 poster presentations and many opportunities for young researchers to enhance their network. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://www.encals.eu/news/encals-meeting-2015-dublin/ |
| Description | General research dissemination videos on YouTube |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Multiple videos on YouTube, responding to interviews on ALS research |
| Year(s) Of Engagement Activity | 2014,2015,2016 |
| URL | https://www.youtube.com/results?search_query=ammar+al-chalabi+als |
| Description | JNNP Podcast |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I was interviewed for a podcast about our recent finding that genetic variants that increase ALS risk, also lower the age of onset. Our paper was Editor's Choice. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Joint JPND Consortia Meeting, London Heathrow |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | Joint JPND Consortia Meeting, 06 - 07 October 2014, London Heathrow: In October 2014 a 1.5-day Joint JPND Consortia Meeting was organized by Project Coordinator (UK1) in London Heathrow, UK. The new format of involving four different JPND-funded project consortia (STRENGTH, SOPHIA, ALS-CarE and NEEDS in ALS) and compiling a meeting programme out of thematic sessions across four projects was a great success and all project coordinators are willing to continue this in the future. Fifty stakeholders including project coordinators, project partners, external collaborators, as well as special guests attended the sessions over two days in London. |
| Year(s) Of Engagement Activity | 2014 |
| Description | Keynote presentation at International Symposium of ALS/MND Associations |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Extensive discussion of the content Invitations to speak at further conferences, two invitations to write reviews for Nature Reviews Neurology (both taken up), invitation to submit paper to Lancet Neurology and to visit the offices. |
| Year(s) Of Engagement Activity | 2012 |
| Description | Lecture tour for researchers, patients and clinicians to South America |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Lectures and Question and Answer sessions were held at several locations in Uruguay and Argentina, including a university in Montevideo, 3 universities in Buenos Aires region, and a hotel in Buenos Aires city. The sessions included simultaneous translation Spanish and English and were live streamed on Facebook, as well as remaining available now. The question and answer session was with patients and carers, and lasted nearly two hours. The entire trip was coordinated by the ELA Association, a South American ALS association, which is now affiliated with the international alliance of ALS/MND Associations. |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://www.asociacionela.org.ar/index.php/pregunta-a-los-expertos-1 |
| Description | MND Connect |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Patient-researcher-clinician question and answer session also live-streamed |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.youtube.com/watch?v=KRb1HWv08gQ |
| Description | MNDA Legacy Event 2019 |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Tour of labs and clinics with talks by researchers and clinicians |
| Year(s) Of Engagement Activity | 2019 |
| Description | MNDA Legacy Event September 2018 |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Supporters |
| Results and Impact | The event was to educate the general public and those engaged with the MND Association about the research done that is funded by the MNDA, with the aim of increasing knowledge and encouraging a legacy to such research, |
| Year(s) Of Engagement Activity | 2018 |
| Description | MNDA Legacy Event at King's College London |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Between 40 and 70 people attended each event, consisting of research presentations, a tour of the labs, and an Ask the Experts session. The events were to raise awareness of our research, to improve donations to the patient organisation (MNDA), and to improve public understanding of our clinical and research programme. Increased donations have been reported, and feedback shows a high demand for future events. |
| Year(s) Of Engagement Activity | 2017,2018 |
| Description | MNDA Legacy Video |
| 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 | During the MNDA legacy event a video was shot with the purpose of engaging with the public as much as possible. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://youtu.be/gbESPsGZyZo |
| Description | MNDA information video on our research |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | A YouTube video posted also on the Motor Neurone Disease Association website, describing our research. |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://youtu.be/tKz81aFVB04 |
| Description | Media campaign over months for an MND Translational Research Institute |
| 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 | Media (as a channel to the public) |
| Results and Impact | An orchestrated campaign with multiple interviews on BBC Breakfast (three interviews), BBC radio channels, and the Sunday Express (was the Express campaign for several months, until success). The campaign was to influence government policy on research into motor neuron disease. Government agreed to fund a £50m 5 year vision for coordinated MND research nationally. The campaign has also been seen and copied in other countries and was described by Business Secretary Kwasi Kwarteng, as "a textbook parliamentary campaign". An example URL is given below but many exist. |
| Year(s) Of Engagement Activity | 2020,2021,2022 |
| URL | https://twitter.com/BBCBreakfast/status/1330796880888999938 |
| Description | Ministerial Roundtable on MND |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | This was a ministerial roundtable on MND convened by NIHR as a result of a parliamentary debate, itself a result of a petition and media campaign to improve MND research to a cure. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Mitsubishi Tanabe Pharma workshop on clinical staging measures in ALS |
| 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 | A formal workshop on different outcome measures for clinical trials in ALS, and specifically the benefits of clinical staging systems. Clinical staging (and specifically King's Clinical Staging for ALS) was regarded as a major benefit for clinical trials and the basis of a research output (two poster presentations and a platform presentation) from the pharmaceutical company at the December International ALS Symposium in Dublin. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.als.net/news/global-als-research-progress-a-report-from-2016-international-symposium-in-d... |
| Description | NIHR MND Engage |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | A study day on PPI |
| Year(s) Of Engagement Activity | 2019 |
| Description | New Zealand Inaugural MND Talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | I gave the plenary talk at the inaugural MND New Zealand research symposium which sparked multiple questions and disussions |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://anzasw.nz/events/motor-neuron-disease-mnd-new-zealand-research-conference-2019/ |
| Description | Parliamentary Debate on MND Research |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | On 12 July 2021, a parliamentary debate was held on our vision for a UK MND Translational Research Institute. This was a vision initially started by two patients with me, and developed by a coalition of patients, patient charities, scientists and industry partners. The debate was one component of a campaign which led to agreed government funding of £50m over 5 years. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.youtube.com/watch?v=SgE1JfFrl20 |
| Description | Scientific Advisory Board and Workshop for Platform Trials at the MGH Healey Center |
| 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 | Current clinical trials are performed sequentially in ALS, which is a very slow method for a devastating fatal disease. Platform trials offer a perpetual trial design, with 3:1 active to placebo participation, and multiple simultaneous trials, greatly accelerating drug discovery and improving patient participation. This board and series of workshops aims to make such trials a reality in ALS. |
| Year(s) Of Engagement Activity | 2018,2019 |
| Description | Staging presentation at Cytokinetics meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | About 220 participants attended in person, with more attending online. This was a set of three presentations on outcome measures for ALS clinical trials, with major audience participation, including voting on different measures. The number of people stating they would incorporate clinical staging as a routine part of their everyday practice increased from 5% to 25% by the end of the discussion. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://alsmndmeasures.com/ |
| Description | TRICALS training |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Training in clinical staging for ALS for members of the TRICALS consortium. An analysis of responses from the training has been submitted for publication. |
| Year(s) Of Engagement Activity | 2014,2015,2016 |
| URL | https://www.tricals.org/#1487071717028 |