Neurodegeneration
Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration or death of nerve cells, and include Alzheimer's disease and other dementias, Parkinson's disease, Huntington's disease, Motor Neurone Disease, Creutzfeldt-Jakob disease and Multiple Sclerosis. Of these, the dementias are responsible for the greatest burden of disease, with Alzheimer’s disease representing over 60-70% of the cases. Neurodegenerative diseases are strongly linked with age and the UK and other European countries have an increasingly ageing population. Currently, 16% of the European population is over 65, with this figure expected to reach 25% by 2030. In the UK it has been estimated that dementia alone costs the economy £17 billion a year.
- MRC Strategic Review of Neurodegeneration
- MRC/Wellcome Trust Joint Call in Neurodegeneration
- UK Initiatives
- International initiatives – JPND and COEN
MRC Strategic Review of Neurodegeneration
In 2008 the MRC published its Strategic Review of Neurodegeneration. The central recommendations from this review were to:
- strengthen biological research into disease origins and mechanisms with a view to developing new therapeutic approaches
- improve training and research capacity
- provide support for a strategic co-coordinated network that would address the key barriers to progress in this field.
The review is available here.
MRC/Wellcome Trust Joint Call in Neurodegeneration
The MRC and the Wellcome Trust launched a joint call in neurodegeneration in 2008 to stimulate high-quality, collaborative and multidisciplinary research that would advance our understanding of the biological processes underpinning neurodegenerative diseases.
Three new innovative and collaborative research programmes were supported under this call. These multidisciplinary research programmes are focused on providing a better understanding of the causes of neurodegenerative diseases - Alzheimer's disease, frontotemporal dementia, Parkinson's disease and motor neurone disease - in order to develop better approaches for early diagnosis and therapeutic interventions for these diseases.
The multidisciplinary collaborations bring together leading academic research teams from around the UK, as well as leading international groups and pharmaceutical companies. Details of the programmes are below:
- Mechanisms of neurotoxicity of amyloid aggregates
- PI: P St George-Hyslop, University of Cambridge
The accumulation of one or both of the two proteins amyloid beta and tau is a characteristic feature of a number of neurodegenerative diseases including Alzheimer's disease. Professor St George-Hyslop and colleagues from Cambridge, Bristol, Max-Planck and Toronto aim to understand how this accumulation results in the death of brain cells using novel methods from physics, chemistry and biology. This information will allow the creation of accurate and sensitive diagnostic tests and new ways to treat diseases.
- The role of RNA-processing proteins in neurodegeneration
- PI: C Shaw, MRC Centre for Neurodegeneration, King’s College London
Recent research on motor neurone disease and frontotemporal dementia has shown that RNA-processing proteins are deposited in degenerating nerve cells and that rare mutations in three known genes cause a genetic form of these diseases. Using these discoveries, Professor Shaw and his colleagues from the MRC Centre of Neurodegeneration Research at King's College London, Manchester, University of California San Diego, Cambridge and Dundee will model key aspects of the human disorders, allowing them to explore fundamental disease mechanisms and identify new therapeutic targets.
- Understanding Parkinson's disease - lessons from biology
- PIs: N Wood, J Hardy, A Schapira, University College London
The cause of Parkinson's disease is unknown, although it is clear that it is a disease of ageing and there are now some established genetic risk factors. To understand how these factors combine, Professors Wood, Hardy and Schapira and colleagues from UCL, Dundee and Sheffield aim to dissect and understand the genetic architecture of Parkinson's and to identify and characterise the biochemical pathways involved in the earliest stages of the disease.
UK Initiatives
MRC-DH Summit on Dementia Research
Following the publication of the Department of Health’s National Dementia Strategy in 2009, the MRC and DH jointly convened a Ministerial Summit on Dementia Research, which took place on 21 July 2009. The meeting examined research into cause, cure and care for dementia, highlighting gaps in knowledge and new opportunities for the future. The independent report of the event is now available.
A cross- agency Ministerial Advisory Group on Dementia Research (MAGDR) was set up in 2010 to consider ways to improve the volume and impact of dementia research. The Report of Priority Topics in Dementia Research was published in April 2011 may be found here. Details of the related National Institute for Health Research (NIHR) themed call for research on dementia may be found here: http://www.nihr.ac.uk/research/Pages/Dementia.aspx
International initiatives – JPND and COEN
Joint Programming in Neurodegeneration, and in particular Alzheimer's (JPND)
MRC is a leading partner in a European strategy aimed at co-ordinating national efforts in neurodegenerative research across the biomedical and social spectrum. This is being conducted through a ‘Joint Programming’ approach between the 25 participating member states, which was formally launched in April 2010. The ultimate goal of the Joint Programme on Neurodegenerative Disease (JPND) is to accelerate progress in understanding the causes of these debilitating conditions, leading to not only early diagnosis and the development of new treatments and prevention, but also the provision of more effective medical and social care to improve the quality of life for patients and care givers.
In early 2012 the JPND published a strategic research agenda for neurodegenerative diseases encompassing basic, clinical and socio-economic research. The downloadable JPND Research Strategy was developed under the leadership of MRC. The next step is to seek to implement this agenda by proposing innovative ways of pooling expertise and resources to address the fragmentation and duplication of current research efforts across Europe.
In May 2011 a call was announced for multi-national, collaborative research projects of up to 3 years that will add value to existing research by developing novel approaches to improve and harmonise the use of biomarkers for neurodegenerative disorders. Full details of the transnational call including the results are available through the JPND website.
Centres of Excellence Network in Neurodegeneration (CoEN)
In June 2010 MRC joined forces with the German Centre for Neurodegenerative Diseases (DZNE) and the Canadian Institutes of Health Research (CIHR) to launch a new joint initiative to develop productive links between their respective centres of excellence of neurodegenerative research. These founding members were joined by VIB (Flanders Institute for Biotechnology), the Health Research Board/Science Foundation Ireland (HRB/SFI), and the Ministry of Health Italy (Ministero della Salute, MDS) in October 2010. The aim of the initiative is to build productive links between research groups within centres of excellence in neurodegeneration, in partner countries, in order to add value to investments and accelerate progress in understanding neurodegenerative diseases and help identify new approaches for treatment.
The first call for pilot proposals under this initiative was launched in February 2011, with a view to addressing key barriers to progress in the field and to provide a platform for future collaborative studies. Each pilot would be up to 24 months in duration. In July this year eight collaborative projects, totalling £3.7m, were funded for research spanning the development of new disease models, the identification of biomarkers and the harmonisation of methodologies for clinical studies. These projects bring together a wealth of resources and expertise from a number of large research institutes in different countries to tackle scientific questions that are key to the advancement within the field.
Of the eight proposals funded five involved teams from the UK. Further information on the call and CoEN can found on the initiative website www.coen.org
Plans for the second phase of CoEN are underway.
Funded Projects
Standards for determining the vascular contribution to neurodegeneration
Lead: Joanna Wardlaw (MRC Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK)
Martin Dichgans (DZNE, Munich, Germany)
Eric Smith (University of Calgary, Canada)
The GENetic Frontotemporal Dementia Initiative (GENFI): a new multi-centre platform for the study of frontotemporal lobar degeneration
Lead: Martin Rossor (University College London, UK)
Giovanni B. Frisoni (IRCCS, Brescia, Italy)
Torik Ayoubi (VIB, Leuven, Flanders)
Mario Masellis (University of Toronto, Canada)
Identification of generic supressors of proteinopathies
Lead: David Rubinsztein (University of Cambridge, UK)
Joerg Gsponer (University of British Columbia, Canada)
Mitochondrial dysfunction and susceptibility to Parkinson’s disease: New models of pathogenetic interactions
Lead: Donato A. Di Monte (DZNE, Bonn, Germany)
Anthony H.V. Schapira (University College London, UK)
David S. Park (University of Ottawa)
Fabio Blandini (IRCCS, Milan, Italy)
C. elegans models of mitochondrial deficiency in the nervous system
Lead: Daniele Bano (DZNE, Bonn, Germany),
Mario de Bono (MRC Laboratory of Molecular Biology, Cambridge, UK)
Siegfried Hekimi (McGill University, Canada)
Early synaptic plasticity and network dysfunction in transgenic (tg) rat models of Alzheimer’s disease (AD)
Lead: Michael Rowan (Trinity College, Dublin, Ireland)
Claudio Cuello (McGill University, Canada)
Martin Fuhrmann (DZNE, Bonn)
Immune subtype in Parkinson disease
Lead: Thomas Gasser (DZNE, Tubingen, Germany)
Antonio P. Strafella (University of Toronto, Canada)
Integrated approach to identify novel genes for frontotemporal lobar degeneration
Lead: Marc Cruts (VIB, Antwerp)
Christian Haass (DZNE, Munich, Germany)