NIHRDataInsights/HRCSData huggingface dataset:
Title: Defining disease progression in ALS: A novel analytic approach using existing clinical and imaging datasets.
Funder: Motor Neurone Disease Association

Abstract: Amyotrophic Lateral Sclerosis (ALS; also known as Motor Neurone Disease, MND), is a progressive neurodegenerative disease which causes weakness, muscle wasting and breathing difficulties. Most patients die within 2 to 3 years of first symptoms Although conventional brain magnetic resonance imaging (MRI) scans are often normal in people with ALS, more sophisticated MRI techniques have shown changes in the structure of the brain. A limitation of even the most recent MRI techniques is that they provide a snapshot of the brain at a single moment in the course of the illness. Only a description of how these MRI changes evolve over time as the disease advances will tell us how the nerve cell damage is evolving area by area in relation to the individual's symptoms This type of information could be obtained by collecting several MRI scans from the same patients over time, but the nature of the disease makes it challenging to acquire scans over several years in the same patient By contrast, this studentship project will use MRI scans that have already been obtained from many studies at King's MND Centre over the last 16 years. By applying new concepts in medical computing to this data the sutdent will identify how MRI changes evolve in sequence, even using scans done on a single occasion. This will allow the student to integrate imaging information with clinical features, linking insights into the evolution of physical changes in the brain with clinical features to develop a new and objective method to'stage' disease progression and to detect brain abnormalities early in the disease. The student will experience research training within an inter-disciplinary team of ALS clinicians working with experts in medical computing and neuroimaging, providing core skills through which to persue a career in a growing and critically important area of ALS research.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Development of an antisense oligonucleotide based strategy to manipulate RNA editing of AMPA receptor subunits in cell lines and motor neurones
Funder: Motor Neurone Disease Association

Abstract: Understanding the causes of motor neurone death is pivotal for developing treatments against MND/ALS. Glutamate is a chemical released by neurones to stimulate neuronal activity, however high levels of glutamate can kill neurones through a mechanism known as excitotoxicity. Glutamate acts on specific assemblies of proteins at the cell surface known as receptors. These receptors form channels in the cell membrane and the action of glutamate causes the channels to open and allow ions (such as calcium) to pass in and out of the cell. Excessive calcium entry through glutamate receptors (during excitotoxicity) can cause neurones to die. Glutamate receptors exist in different families and we are investigating one called the AMPA receptor or AMPAR. Normally specific components of the AMPAR prevent calcium entry and the cell is able to control this process by editing the short sections of draft message (RNA) before it is used to build proteins. Faulty RNA editing produces unedited AMPARs and allows excessive calcium entry through AMPARs. The result is disastrous for motor neurones. When the efficiency of the RNA editing process is reduced in mice, they show symptoms of motor neurone degeneration and there is a high level of unedited GluA2 in the motor neurones of ALS patients. We propose to use short sequences of DNA (antisense oligonucleotides) to make the RNA editing process in AMPARs run more effectively and reduce the susceptibility of neurones to cell death. This work will involve the use of cell lines and motor neurones grown in the laboratory as model systems to test our antisense oligonucleotides. The three main objectives will investigate whether antisense oligonucleotides targeted at the RNA editing process can: (i) increase the stability of the AMPAR RNA structure for editing. (ii) improve the efficiency of the RNA editing machinery. (iii) reduce the vulnerability of motor neurones to excitotoxic cell death. Importantly, successful outcomes from this work may lead to the development of a new strategy to reduce motor neurone death, support further testing in animal models and lead to potential clinical treatments against MND/ALS.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;5.2 CELLULAR AND GENE THERAPIES
Health categories: NEUROLOGICAL
Title: Pain assessment and management for patients with advanced dementia nearing the end of life
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Dementia is a growing public health problem; increasing numbers of people are living, and dying with this condition. The importance of high-quality care for patients with dementia at the end of life is well-recognised. However, it has been reported that patients with severe dementia may not have their pain assessed and treated properly as they cannot communicate their pain and discomfort effectively. The issues in assessment and management of pain in patients with severe dementia who are approaching the end of life must therefore be examined to enable strategies to be developed which will improve the quality of care these vulnerable patients receive. The proposed study aims to examine the main issues in pain assessment and management for these patients in Northern Ireland. This study will use interviews to determine the views of healthcare professionals (doctors, nurses, nursing home staff) and of carers of people with dementia who have since died. The key issues identified from these interviews will be used along with the previous research which has been conducted in this area to identify model(s) for the assessment and management of pain nearing the end of life tailored to the setting of care (patient’s home, nursing home, hospital or hospice). These models will then be presented at a one day workshop to an audience of healthcare professionals, carers and the dementia and palliative care organisations. The feedback obtained from this workshop will be used to refine and develop the models which will then be tested for patients with severe dementia across the range of care settings. We will obtain feedback from the healthcare professionals and carers involved in piloting these models. Further funding may then be sought to undertake a larger-scale and more detailed evaluation of the developed models.


Research activity codes: 7.2 END OF LIFE CARE;7.3 MANAGEMENT AND DECISION MAKING
Health categories: NEUROLOGICAL
Title: Promoting informed decision making and effective communiction through advance care planning for people living with dementia and their family carers
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: The patient’s right to self-determination has become a key ethical principle in dementia care. Advance Care Planning (ACP) is in line with the principle of self-determination where an ACP document is a written or verbal record of a person’s choices about their future medical care. Regrettably, given the relative importance of ACP for people living with dementia, the available research demonstrates that the provision of ACP for persons living with dementia is poor. In Western countries a substantial number of individuals living with dementia are admitted to a Nursing Home before death and are often transferred to hospitals where aggressive and overly burdensome treatments are provided. In this situation family carers are often required to make many difficult and emotionally burdensome decisions about whether or not to proceed with life sustaining treatments which may lead to death when they are not prepared to make such decisions. The purpose of this study is to evaluate the application of a best-practice ACP model for individuals living with dementia in a sample of nursing homes in Northern Ireland. Specific outcomes examined will include family carer satisfaction in decision making regarding options for care; family carer’s overall satisfaction with nursing home care; assessment of comfort care in nursing homes for persons living with dementia; and, impact the ACP model has on the use of acute care services. As part of this study, the lived experience of family carers required to make treatment decisions on behalf of a family member living with dementia will be explored. It is anticipated that this study will provide evidence towards the development of practice in nursing homes that will support family carers in decisions that will promote person-centred care for individuals living with dementia


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: NEUROLOGICAL
Title: Risk Communication in Dementia Care
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: A major issue in dementia care in Northern Ireland is the high number of people being admitted to long-term residential and nursing home care. One of the main challenges in addressing this issue is a tendency to avoid risk on the part of the Prof.essionals and family members, whereas many people with mild to moderate dementia would prefer to remain in their own homes, facing the risks involved. A practice issue underpinning this problem is lack of clear risk communication. Prof.essionals, family members and those with dementia may conceptualise risks in various ways and may use the word ‘risk’ differently. This study addresses this issue by (1) identifying concepts of risk used by Prof.essionals, family carers and people with mild to moderate dementia; (2) identifying the risk factors that they encounter and address most commonly in dementia care decisions about long term care; and (3) exploring in details how Prof.essionals communicate about the likelihood of some ‘risks’ (undesirable outcomes) using words, numbers and visual methods for presenting probabilities. As well as addressing a high priority policy and practice issue for health and social care in Northern Ireland, this study will build on the international expertise of the Harding Centre for Risk Literacy and the Centre for Adaptive Behaviour and Cognition at the Max Planck Institute for Human Development in Berlin (MPIB) in relation to risk communication. MPIB is world-leading in the study of risk and decision making and a number of studies have been undertaken on risk communication in health care. The project will develop collaboration between the Max Planck Institute for Human Development and the University of Ulster on risk and decision making in health and social care with future benefit for the service and research in Northern Ireland.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: NEUROLOGICAL
Title: The development of a comprehensive medicines management approach for persons with dementia in primary care
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: The term 'medicines management' usually means the prescribing, review, administration and adherence (compliance) associated with medicines. We already know that older people may continue to receive medicines that may not be appropriate, without any review and their adherence (compliance) with treatment may be poor. However, in persons with dementia (PWD), very little is known about the type of medicines they are prescribed, the quality of the prescribing and adherence with medicines. The little research which has been done has been conducted in care homes. In this project, we will examine the prescribing, review and administration of medicines (including adherence) in PWD who live in their own homes. We will do this by undertaking a three-phase project. The first phase will look at what medicines are used by PWD who are being prescribed for by a general practitioner (GP). This information will be taken from a database that is held by Business Services Organisation (BSO), which processes all prescriptions that are dispensed by community pharmacists in N. Ireland. We will look at what is being prescribed and we will use a tool that will help us assess the quality of that prescribing. In the second phase, we will invite PWD carers, GPs and community pharmacists to take part in an interview to discuss medicines management and what is important from their point of view. We will analyse the content of the interviews to find out what might be helpful in medicines managements for PWD and what might be a problem. From these results, we will develop an approach to devise a way in which GPs, community pharmacists, PWD and carers can work together to improve medicines management. In the final phase of the project, we will try this approach in a small number of GP practices and community pharmacies.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: NEUROLOGICAL
Title: Identification of genetic modifiers in amyotrophic lateral sclerosis by next generation sequencing (Sheffield INSPIRE 2014).
Funder: Motor Neurone Disease Association

Abstract: This grant was to enable a medical student to gain experience of biomedical research during a summer vacation. The aims were: (1) analysis of sequencing data from next generation sequencing in 200 MND cases; (2) validation of findings, including confirmation that changes segregate with disease in families, as mutations with a real effect on disease are less likely to be found in unaffected relatives of MND patients.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Challenge 12: UnTangle
Funder: Alzheimer's Research UK

Abstract: Overall objective:To develop a physiologically relevant human stem cell-derived neuronal assay to predict the efficacy and unexpected pharmacological effects of new chemical entities and biologics targeting tau in Alzheimer’s disease. Key deliverables:An assay which: •Models tau aggregation, seeding and the related formation of insoluble hyper-phosphorylated tau with spread/transmission between cells •Links to network dysfunction and neurotoxicity •Provides the ability to research and predict the efficacy and unexpected pharmacological effects of novel compounds and antibodies •Is not already available e.g. current models of tau phosphorylation Phase 1: •Acquisition of cells from patients, mutation-carriers and healthy subjects •Evidence of differentiation into neurons and glia, synaptic and neuronal markers, the presence of tau isoforms and activation states •Details regarding materials and substrates planned to assess in Phase 2 •Investigation of potential of the assay for electrophysiology •Consideration of commercial strategy Phase 2: Development of an assay that: • Can express different tau species, cleavage products, conformational changes, aggregated and phosphorylated tau • Expresses synaptic markers and/or markers of plasticity (e.g. synaptophysin, NMDA receptors, PSD95) • Is reproducible, scalable and has potential for use in screening • Shows defined disease phenotypes in control and disease state iPS cells Validation of the assay through: • High content based imaging focusing on e.g. neurite length and branching, synapse density and shape, granularity measures • Electrophysiology to measure activity in the culture system(s) The system should demonstrate the capability to measure reliably: • Neuron-neuron transmission of aberrantly folded tau (the ‘prion hypothesis’), including the release and endocytic re-uptake of tau • Neuronal: microglial interaction • Neuro-inflammatory responses to aberrantly folded tau • Mitochondrial function • Synaptic activity (e.g. intracellular, extracellular, network) • System should be developed and validated in within the scope of commercial use by the pharmaceutical industry


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: NEUROLOGICAL
Title: Investigating novel protective mechanisms in motor neurons
Funder: Motor Neurone Disease Association

Abstract: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects a specific population of nerve cells, called motor neurons, mainly localised in the spinal cord. Little is known about the causes of ALS and no affective treatments are available. In order to meet the challenge of developing therapy for the disease it is vital that we understand why motor neurons die while other cells in the nervous system are not affected. One of the theories is that at the very earliest stages of the disease, motor neurons are more sensitive to stress caused by an imbalance in the amount of oxygen in cells, also known as oxidative stress. Our work has shown that artificially increasing the levels of a gene called Oxr1 can protect neurons from death caused by oxidative stress in cell culture. Significantly we have also shown that in a mouse model of ALS, Oxr1 delays the onset of disease symptoms and increases lifespan. These results suggest that switching-on the expression of Oxr1 at the right time would be beneficial to ALS patients. The aim of this project is to understand more about the role of Oxr1 in the protection against the death of motor neurons in ALS and to determine if it is possible to increase levels of Oxr1 for therapeutic benefit in ALS.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Role of mitochondria in C9ORF72-related ALS/MND
Funder: Motor Neurone Disease Association

Abstract: Defects in a gene named C9ORF72 are found in families who develop MND. Analysis of a large number of, patients revealed that C9ORF72 is actually the most common cause of MND that is currently known. Approximately 1 in 10 of all cases of MND have a defect in C9ORF72! It is essential that we find out how this defect causes MND. Mitochondria are tiny, but essential, parts of every cell that are believed to contribute to the development and progression of MND. Mitochondria provide cells with energy, and ensure the normal function of motor neurons by regulating essential biochemical pathways. We think mitochondria are involved in MND caused by C9ORF72 as well. With this project we want to understand the function of the C9ORF72 gene, and to determine how defects in this gene cause MND. The first aim is to find out if C9ORF72 damages mitochondria. We already have some evidence that suggests it does. The second aim is to investigate the binding of C9ORF72 to two mitochondrial proteins that we have found. We believe that this is likely to be involved in the damage to mitochondria. If this is so then therapies that modify the binding of C9ORF72 to these proteins could form the basis of a new treatment for MND. Accordingly our third aim is to establish how C9ORF72 damages mitochondria and how the mitochondrial proteins that bind to C9ORF72 are involved. This project will be carried out in the Sheffield Institute for Translational Neuroscience (SITRAN). In SITRAN we try to understand what is happening inside the bodies of MND patients by investigating the causes of disease in cell models and patient samples grown in laboratory dishes. After finding faults that cause disease in those cells we can start to design treatments to repair those faults and develop new ways of diagnosing disease. Our pilot studies have provided the first clue that mitochondria could be targeted as a new treatment for people with MND. It is only by testing this idea in the laboratory that we can tell if the treatment stands a good chance of working in human patients, and that is what we want to do in this project.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: 2011 Cochrane Fellowship: Herbal Medicinal products or preparations for Neuropathic Pain and Fibromyalgia
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Chronic painful conditions are disabling, leading to significant reductions in quality of life that can be ameliorated by effective treatment. There is evidence from population based surveys that people with chronic pain are likely to try herbal treatments and it is therefore important to determine the efficacy and safety of herbal medicines in the treatment of such conditions. There are an increasing number of trials reporting on the use of avocado-soybean unsaponifiables (ASU) in the treatment of specific chronic pain conditions, with reasonable evidence of its effect in osteoarthritis, with a number needed to treat (NNT) of 3.6 (1). Therefore, performing a Cochrane review to investigate the current existing evidence for the usefulness of ASU in chronic pain would be valuable. Indeed, a previous Cochrane review looking at a range of herbal therapies for treating osteoarthritis concluded that evidence for ASU in the treatment of osteoarthritis was promising as observed in 2 of the studies included in the review (2). Further studies would be desirable to verify efficacy. These promising results in patients with osteoarthritis have been observed when ASU is given as a mixture made up of one-third avocado oil and two-thirds soybean oil. These studies suggest that ASU have a symptom modifying effect in osteoarthritis; however, the efficacy and safety of ASU on chronic pain conditions have not been systematically reviewed. This would benefit patients and clinicians in making judgements about the efficacy and safety of ASU across a range of chronic pain conditions. Findings from an Australian internet-based survey looking at self-management of low back pain discovered that 78% of respondents reported using analgesic medication as their most common initial reaction (3). Given that nonsteroidal anti-inflammatory drugs (NSAID) have been implicated in renal, gastrointestinal and cardiovascular harm, reducing their use as a result of ASU use would benefit patients with chronic painful conditions, such as this, who would possibly turn to NSAID for pain management. Primarily, this review will look at the quality of the evidence of the effectiveness of ASU in the treatment of chronic pain. This will clarify the strength of the evidence base, therefore allowing patients and clinicians to make evidence based decisions on the benefits and/or risks associated with the use of ASU for chronic pain.


Research activity codes: 6.8 COMPLEMENTARY
Health categories: NEUROLOGICAL
Title: Carer involvement in the general hospital care of people with dementia: developing a framework for planning and implementing practices that meet the needs of patients, carers and staff.
Funder: Department of Health (England)

Abstract: Dementia is common in general hospitals but care is often poorly managed. Involving carers in care planning and delivery could help to improve care, but there is no consensus on what carer involvement means, or on preferences for involvement. This research will use quantitative and qualitative methods to explore carer involvement (preferred and actual) among patients, carers and staff, and methods of promoting satisfactory involvement. Outputs from the research will be developed into a framework to inform the planning and implementation of carer involvement practices that meet the needs of patients, carers and staff.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL