Neurodegeneration
Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration or death of nerve cells. They 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
- Trans-national 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.
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
UK Brain Banks network
The MRC has led the establishment of an independent and coordinated UK Brain Banks Network. It will provide high quality brain tissue to scientists and clinicians to carry out cutting edge research into neurodegenerative diseases as well as supporting research in psychiatric conditions and other major neurosciences research.
MRC-DH/NIHR
Following the launch of the Department of Health’s National Dementia Strategy in 2009, the MRC and DH jointly convened a Ministerial Summit on Dementia Research in July 2009. The meeting examined research into cause, cure and care for dementia, highlighting gaps in knowledge and new opportunities for the future, (see the independent event report). Inter-agency working continued and in April 2011 a Ministerial Advisory Group on Dementia Research (MAGDR) published a Report which recommended ways to improve the volume and impact of dementia research with work-streams channelled to topic-specific Action Groups for implementation. MRC led the development of the report on research priorities. This work now comes under the umbrella of the Prime Minister’s Challenge on Dementia which was launched in March 2012 order to push further and faster progress in the prevention, treatment and cure of dementia.
The Challenge focuses on three key strands: i) improvements in health and care; ii) research; and iii) dementia friendly communities that understand how to help. A Champion’s Group has been established in each, reporting to the DH National Dementia Strategy Implementation Programme Board, with MRC contributing to the research group.
The PM Challenge entails a commitment to more than double overall Government funding for dementia research to over £66m by 2015, through the combined efforts of MRC, the National Institute for Health Research (NIHR) and Economic and Social Research Council (ESRC). MRC has identified four key activities that will help ensure a doubling of spend from £16.6m in 2010/11 to £33.2m by 2014/15, in the context of our CSR target of > £150M investment in neurodegeneration research between 2011/12 to 2014/15. These encompass enhanced investment in the Neuroscience division of the MRC Laboratory of Molecular Biology, the establishment of a brain imaging programme in UK Biobank, support for the donation of brain tissue to the UK Brain Banks network, and investment in the trans-national collaborative programmes JPND and COEN (see below).
Trans-national initiatives – JPND and COEN
In 2011 MRC provided £2m to fund UK participation in 8 cross-border projects under the transnational JPND and CoEN initiatives, and in July this year allocated a further £3m for new calls for these collaborative efforts in dementia and neurodegeneration research.
An overview of these two initiatives follows. Specific details, including of funded projects, are available through the JPND and CoEN initiative web sites.
The EU Joint Programme – Neurodegenerative Disease Research (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 27 participating member states, which was formally launched in April 2010. JPND aims to increase coordinated investment between participating countries in research aimed at finding causes, developing cures, and identifying appropriate ways to care for those with neurodegenerative diseases.
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. JPND partners are now engaged in implementation of this agenda by proposing innovative ways of pooling expertise and resources to address the fragmentation and duplication of current research efforts across Europe. Review the first phase of the plan, which covers both calls for proposals and other forms of trans-national collaborative activity. Three JPND calls have been launched to date.
Centres of Excellence Network in Neurodegeneration (CoEN)
The COEN initiative was established in June 2010 between MRC, the Canadian Institutes of Health Research (CIHR) and the Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE, Germany). The initiative was subsequently joined by Flanders, Ireland, Italy, Spain and the Slovak Republic.
The overall aim of the initiative is to build collaborative research activity in neurodegeneration research across borders, focusing on adding value to the expertise and critical mass already established within national centres of excellence (CoE). COEN is aligned with the broader Joint Programming Initiative in Neurodegeneration (JPND), although it operates as an independent entity.
The first phase of the initiative involved a call for pilot projects to address barriers to progress in the field, linking CoEs in two or more countries. Eight collaborative projects totalling £3.7m (€4.6m) were funded, including research projects which spanned the development of new disease models, the identification of biomarkers and the harmonization of methodologies for clinical studies.
The second phase of COEN is calling for ‘pathfinder’ grants seeking innovative approaches to better understand disease mechanisms and provide new avenues for therapeutic development, with the potential for “programme” level support to take forward successful pathfinders.