NIHRDataInsights/HRCSData huggingface dataset:
Title: Structure-function studies on ALS associated C9orf72 protein
Funder: Motor Neurone Disease Association

Abstract: The C9orf72 gene provides instructions for making a protein that is found in many tissues but whose function is unknown. The C9orf72 protein is produced in many regions of the brain. Within nerve cells (neurones), the protein is found in the fluid surrounding the nucleus (the cytoplasm). Additionally, the C9orf72 protein seems to be located in specialized structures called presynaptic terminals, found at the tips of neurons. Mutations in the C9orf72 gene have been shown to be the cause of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). It is a genetic (autosomal dominant) neurodegenerative disorder characterized by adult onset of ALS and/or FTD in an affected individual. There is high intra-familial variation. ALS is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTD is characterized by frontal and temporal lobe degeneration associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. The defect in the C9orf72 gene can be caused by a large expansion (single or multiples times) of six building blocks (hexanucleotides) in the region which controls the production of the protein and hence likely to cause disruption in cell function. It is unclear how decreased or altered C9orf72 protein causes the signs and symptoms of ALS or ALS-FTD. In the proposed project, we intend to determine the three-dimensional molecular structure of the C9orf72 protein in order to understand the molecular function. This study could lead on to decipher the interacting partners responsible for the control of the disease and the long term possibility for the design of compounds to halt the progression of the disease using a rational ‘molecular structure-based drug design’ approach and ‘protein engineering’ techniques.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL
Title: ASSFAP: A seven stepped facilitated action planning process for recognising and meeting the spiritual needs of people with advanced dementia.
Funder: Arts and Humanities Research Council

Abstract: In 2010 the applicant completed a piece of work funded by the AHRC which looked at the spiritual needs and lives of people with profound learning disability. Understanding the spiritual lives of people with profound and complex learning disabilities: a community oriented action research approach. AH/F011482/1. A product that came unexpectedly out of this study was the ASSFAP: a seven stepped facilitated action plan. This educational and process tool/system was specifically designed to be used by communities to explore, understand and respond to the spiritual needs of people with severe intellectual and cognitive impairments through the use of an action planning system of spiritual care development and delivery. Whilst there are recognisable differences between the two populations, it was felt that this process could be transferred and applied to other settings and that it could provide for the needs of a wide range of people with profound communication difficulties. People with advanced dementia are a group of people, like those with profound learning difficulties, who are often overlooked and can be the subject of poor care through a lack of knowing what to do and how to be with them. This resource provides a method of "doing and being" for those who care for them professionally and within families, which enhances the quality of life of both the carers and the people with communication difficulties. The project presented here focuses on making this resource (ASSFAP) available to the community of carers who look after people with advanced dementia; either those who live either at home, in residential care or in hospital. It comes at a time when the care of frail elderly people has been spotlighted by The Care Inspectorate (formerly the Care Commission) as requiring urgent attention. There is growing concern that care of older people, particularly those with advanced dementia, is being reduced to what has been called "bed and body work" to the enormous detriment of the older person and shame of our society.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: NEUROLOGICAL
Title: Dementia and imagination:connecting communities and developing well-being through socially engaged visual arts practice
Funder: Arts and Humanities Research Council

Abstract: Although people are living longer than ever before, the number of people with dementia is increasing, and 1 in 5 people over 80 will have dementia by 2021. People with dementia and their families often become disconnected from society through the stigmatizing effect dementia has on taking part in everyday activities. Added to this, the current economic climate has meant reductions in many services, and there is often a lack of meaningful activity available to this population. Yet many people with dementia wish to remain within their communities, in the home of their choice, near their family, carers and friends, with the support of health and social care services. This research aims to address the disconnection and marginalisation of people with dementia and explore how the vision for dementia supportive communities might benefit from creative activities. Specifically, it will use a visual art intervention as the catalyst for change for understanding community connectivity, challenging attitudes and promoting well being. Research to date, although limited, suggests a number of potential benefits of arts participation to the quality of life, health and well-being of people with dementia. This project wishes to build on this to address a new area, which will maximise the involvement of, and potential benefit to communities. It will look at how participation in community arts interventions can increase well-being and connectedness between the dementia community and wider society. It will also examine another new area, to further understand the underlying processes that create the connection between arts participation and good outcomes. To realise the aims, the research will be set within three areas of the UK. These consist of ethnically and geographically diverse communities to contextualise the research. In each area our project partners will deliver the same visual arts intervention over a 12 month period to different groups. To understand the impact, the research will assess changes over time in the well-being and social connectedness of people with dementia, and how these changes can in turn have positive effects in communities (facilitate change in societal attitudes and promote participation and inclusion) through social contagion. The processes and outcomes of the research will be assessed using a range of quantitative and qualitative approaches, and will use art, both as a tool for analysis and for visual, creative representations of the results. The research builds on existing relationships and develops new ones with community and policy partners, such as arts organisations, museums, galleries, health and social care practitioners, charities and local government. This will ensure full engagement and maximum benefit and impact for research, policy and practice. It will also contribute towards building future sustainability.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: The arts in dementia care - A Critical Review of cultural and arts practices in dementia care in the UK
Funder: Arts and Humanities Research Council

Abstract: It is generally accepted that the 'arts' improve the lives of those who live with a dementia. Consequently there has been a proliferation of arts based activities for people with dementia. However, there has been little or no critical evaluation of these initiatives. Similarly there has been little work exploring the views of people with a dementia who participate in arts activities. This lack of research has resulted in an uncertainty regarding the approaches that may be most effective. The proposed review will provide a corrective to this lack of clarity. The work will supply an analytical overview of the existing arts and cultural interventions that are used in dementia care. It will map some of the approaches being used and the gaps in research and knowledge concerning the use of the arts for dementia care. Above all, it will seek the views of people living with a dementia and integrate these in the final report. The major outputs arising from the review will include a critical report on current arts based approaches to dementia care that will contribute towards a new critical paradigm for the assessment of arts and culture based approaches to dementia care. In addition, the review will articulate the perceptions of people living with a dementia concerning the value of arts and cultural interventions to their well-being and health and these views will be central to the re-appraisal of prevalent assumptions about the benefits of arts and culture in the lives of those living with a dementia. An additional major output from the 6 month project will be the development of a dedicated website that disseminates findings in accessible language and therefore reaches beyond academic boundaries to people living with a dementia, their carers and the dementia care workforce. The project will benefit from a uniquely qualified inter-disciplinary team comprising: the PI - dr. Hannah Zeilig (a research fellow at both the University of the Arts, London and the University of East Anglia) who has over two decades of experience as a gerontologist and has used numerous arts based approaches with people living with a dementia; Chris Fox who will provide clinical/research guidance and is a leading international dementia researcher and consultant old age psychiatrist and the input of the innovator and pioneer of arts based approaches to dementia care: John Killick.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: NEUROLOGICAL
Title: Corticospinal motor neuron developmental control genes as candidates for human ALS susceptibility
Funder: Motor Neurone Disease Association

Abstract: On average, more than half the risk of developing ALS comes from the particular genetic variations a person carries. This is perhaps surprising since the genetic make-up someone is born with does not change, but ALS comes on in adulthood, not at birth. The reason is likely to be in part because of the way those gene variations lead to variations in the early developmental maturation, growth, and wiring of each person's nervous system, and even subtle variations in that wiring (e.g. reduced number of connections; complexities of the connections; even early age advantages) might make someone more vulnerable to degeneration of those “imperfect” or especially complex but vulnerable neurons and connections in ALS. Genes controlling the development, growth, connections, and refinement of corticospinal motor neurons, the “upper motor neurons” that degenerate along with spinal motor neurons in ALS (and degenerate uniquely in the related motor neuron diseases Hereditary Spastic Paraparesis and Primary Lateral Sclerosis), are therefore strongly motivated candidates as genes for ALS, and even seemingly minor variations in those genes (whether deleterious or even those that might be beneficial early) are likely to affect whether someone is at increased risk for developing ALS. Identifying such ALS association genes might lead to approaches to prevent, slow, or reverse ALS. In a collaboration between Prof. Jeffrey Macklis’ developmental neurobiology lab at Harvard University (who have discovered an increasing set of corticospinal motor neuron developmental control genes in mice) and Prof. Ammar Al-Chalabi’s human ALS genetics lab at King's College London, we will investigate genes already identified (published and unpublished) as controlling the development of the corticospinal motor neuron system, and genes already identified as candidate corticospinal developmental control genes. We will screen those genes for combinations of common variations in 15000 people with ALS and compare this with the results in 30000 people who do not have ALS. We will also screen those genes for rare variations in 1000 people with ALS and compare the results with a similar number of sequences from people without ALS. We will interactively connect the human ALS genetic findings to what is known or can be discovered in mouse corticospinal motor neuron (and related neuron) development. Understanding how variation in these genes modifies risk for ALS will help us to understand what leads to ALS, and to design effective therapies.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: The use of smartphone technology to reduce morbidity and mortality in ALS
Funder: Motor Neurone Disease Association

Abstract: Many people with MND require non-invasive ventilation treatment. In spite of this intervention, they could still have breathing difficulties or other reasons for emergency admission to hospital. Treatment of an MND patient is very specific, and they have different requirements to people with other respiratory difficulties. This grant funds the development of a smartphone app which will self-activate if the phone's owner is admitted to an A&E department. The app will automatically text details of the owner and their location to a relevant medical expert, selecting the texts' recipients from an database which shows who is present in the hospital or 'on call out of hours'. On receipt of such a text, the MND expert can phone the A&E department and provide their advice. A further aim is to develop other app functionality for collection of research and clinical data related to communication and mobility as MND progresses.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: Development of a high throughput gene, environment and epigenetics database and analysis system for international ALS research
Funder: Motor Neurone Disease Association

Abstract: Genetic technology is advancing rapidly. We now have the ability to quickly and cheaply collect huge amounts of genetic information, and because of close collaboration between research groups, to do this in tens of thousands of people. The problem is how to store, handle and easily share this information. For example, the genetic information from just one person will fill a 1Tb hard drive. The information collected across research groups internationally is vast. This cannot be emailed, and most computers are completely unable to open such large files. This makes it difficult to use the information in a constructive way. This project is a collaboration between researchers working in motor neuron disease, and computer scientists working with biological information. We aim to develop a computerized system (a bioinformatics pipeline) that will let researchers easily use genetic, clinical and lifestyle information that has already been collected, and add new information as it is produced. The system will make it easy to see patterns in the relationship between clinical features, lifestyle, and gene variations, to compare genetic variations between groups of people, and to share the information between research groups. The computerized system will be developed in collaboration and consultation with the ENCALS European research group, and the NEALS US-based research group, as well as research consortia within the US, Europe, and internationally, to make sure that it provides solutions that everyone finds useful, and will be widely used. This will make it far easier to find new gene variations affecting motor neuron disease risk, or the pattern of disease a person experiences, to understand how these relate to lifestyle, and to answer new research questions much more quickly than is the case now. This will improve our understanding of motor neuron disease and help in the design of new treatments.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: NEUROLOGICAL
Title: A new conditional BAC transgenic model of C9ORF72-linked Motoneuron Disease to allow direct visualisation and analysis of impaired RNA cellular pathways
Funder: Motor Neurone Disease Association

Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating related diseases without any effective treatment. Recently, a very important discovery demonstrated that an inheritable abnormality in one molecule which exists in all the cells of the brain and spinal cord called C9orf72 causes a large proportion of cases of both diseases. Although we all have two copies of this molecule per cell, one from each of our parents, the inheritance of a single copy of the anomalous C9orf72 is enough to cause ALS, FTD, or both in patients. This suggests that the abnormal C9orf72 molecule has a toxic effect in some brain and spinal cord cells causing them to die and leading to permanent symptoms and eventually death of the patients. In this project we will reproduce these diseases by inserting the abnormal C9orf72 molecule into the cells of the brain and spinal cord of mice. We will label the C9orf72 molecule with different fluorescent tags to enable us to track the toxic molecule as it causes damages in the animal tissues. We will study the tissues of these animals under the microscope to determine how the toxic C9orf72 molecule kills the cells. In addition, due to the different label tags we will put in the C9orf72 molecule, we will determine which other molecules that interact with C9orf72 contribute to its toxic effects. Finally, the design of our model will allow us to halt the expression of the toxic C9orf72 and study if it is possible to recover from the disease usig a therapy targeted at destroying the abnormal C9orf72 molecule.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Using quality adjusted life years in MS
Funder: Multiple Sclerosis Society

Abstract: What is the project about? _x000D_ A quality-adjusted life year (QALY) is a health economic tool used to compare different treatments and interventions â€“ so that the NHS can make decisions on which treatments to fund._x000D_ _x000D_ QALYâ€™s are a generic measurement, however, and donâ€™t take specifics about how MS can impact on a personâ€™s life into account. This means that some treatments and services that could be helpful to people with MS might not be available on the NHS._x000D_ _x000D_ Dr Green will lead a three year project aiming to develop a QALY measurement specifically for people with MS._x000D_ _x000D_ He will:_x000D_ _x000D_ - adapt the Multiple Sclerosis Impact Scaleâ€“29 (MSIS-29), a scale used to assess the physical and psychological impact of MS, to ensure it covers the full impact of MS _x000D_ - develop a QALY specific to MS _x000D_ - conduct a web-based survey of 1000 people in the general population â€“ comparing various measures of quality of life with those of people with MS _x000D_ _x000D_ How will it help people with MS?_x000D_ _x000D_ People with MS face specific challenges that can be poorly understood. A new QALY measurement will take these specific challenges associated with MS into account._x000D_ _x000D_ We hope this will help professionals to make more informed decisions about what treatments and services to fund on the NHS.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: NEUROLOGICAL
Title: What controls the blood brain barrier in MS?
Funder: Multiple Sclerosis Society

Abstract: What is the project about? Under normal circumstances cells and molecules are prevented from entering the brain by the blood brain barrier._x000D_ _x000D_ During an MS attack, the blood brain barrier opens and allows immune cells to enter the brain â€“ where they can attack myelin. Little is understood about what causes the blood brain barrier to open and close â€“ but there is some indication that a class of small molecules called microRNAs may play a role in controlling the blood brain barrier._x000D_ _x000D_ In this three year study, the researchers will:_x000D_ _x000D_ - determine if microRNAs play a role in controlling the blood brain barrier using tissue samples from the MS Society Tissue Bank _x000D_ - use laboratory models of MS to see if changing the levels of specific microRNAs will change the way the blood brain barrier works _x000D_ _x000D_ How will it help people with MS?_x000D_ _x000D_ This is an early laboratory study that will help researchers find out how the blood brain barrier works â€“ and what changes occur in people with MS that cause it to open. Knowledge gained from this study may lead researchers to develop treatments that prevent the blood brain barrier from opening in people with MS.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Long-term effects of bone marrow stem cell transplantation in people with MS
Funder: Multiple Sclerosis Society

Abstract: What is the project about? _x000D_ Bone-marrow transplantation is an experimental treatment for people with severe forms of MS, but we donâ€™t fully understand how it changes peopleâ€™s immune system, and how that affects MS in the long term._x000D_ _x000D_ This three year research project will look at the balance of immune cells before and after bone marrow transplantation in samples taken from around 90 participants in several different clinical trials from around the world._x000D_ _x000D_ Dr Muraro and his team will analyse how the immune systems of participants have changed as a result of bone-marrow transplantation._x000D_ _x000D_ How will it help people with MS?_x000D_ _x000D_ Stem cells are considered a promising potential therapy for some people with MS but there are still so many unanswered questions we have. This research will help us answer some of the very important questions that researchers have about how bone marrow transplantation impacts on people with MS in the long term.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: NEUROLOGICAL
Title: How do mesenchymal stem cells from people with secondary progressive MS differ?
Funder: Multiple Sclerosis Society

Abstract: What is the project about? _x000D_ The aim of this 3 year project is to increase our knowledge about a type of stem cell called mesenchymal stem cells._x000D_ _x000D_ These cells are thought to have the ability to repair and limit damage to nerve fibres of the brain and spinal cord in people with MS._x000D_ _x000D_ To do this mesenchymal stem cells from people with secondary progressive MS will be compared with cells from people without MS._x000D_ _x000D_ How will it help people with MS?_x000D_ _x000D_ Experts believe that transplantation of mesenchymal stem cells could be a good potential therapy for the treatment of secondary progressive MS and that their effectiveness should be tested in a clinical trial._x000D_ _x000D_ A greater understanding of mesenchymal stem cells will be valuable for the design of clinical trials to test these stem cells as a potential therapy for secondary progressive MS.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL