NIHRDataInsights/HRCSData huggingface dataset:
Title: 2019 Doctoral Fellowship: Investigating lymphoid-like structures in the pathogenesis of Multiple Sclerosis
Funder: Public Health Agency, NI

Abstract: Multiple Sclerosis (MS) is an incurable, inflammatory, demyelinating disease of the Central Nervous System (CNS) that causes significant morbidity and disability. Relapsing-Remitting MS (RRMS) is characterised by exacerbations and relative recovery, which is partly reduced by immune-targeting, disease-modifying therapies (DMT). A majority of patients develop Secondary Progressive MS (SPMS) with accrual of permanent disability. Few DMTs have been shown to have even a very modest effect on disease progression and there are no approved DMTs for SPMS in the UK. Northern Ireland has a very high prevalence of MS which encouraged MS research here historically. A very unique collection of CNS tissue from >300 individuals, predominantly MS patients, was collected here. Crucially, all tissues pre-date DMTs and as such, represent the natural history of MS. Furthermore, the collection includes extremely rare tissue from the earliest stages of MS, as well as the largest collection of MS eye tissue globally. Recently, this tissue has resulted in two seminal discoveries of MS pathology. First, a collaboration between UCSF and QUB identified that retinal neurodegeneration occurs very early in MS and that retinal inflammation persists even in very long duration MS (Green et al., Brain, 2010). Second, a collaboration between Swansea University and QUB identified that lymphoid-like structures (LLS) which are known to contribute to cortical grey matter damage in MS, can occur at the very earliest stages of MS (Bevan et al., Ann Neurol, in press). These studies underpin the goals of this proposal, to deeply characterise LLS in early and late MS and determine if these structures also develop in the visual pathway in MS. The senior authors of these two previous studies are co-supervisors/collaborators to ensure the best possible training including periods of time in their research centres in Swansea University and UCSF. Two further collaborators in QUB will support ambitious transcriptomic profiling of LLS using RNAseq. Through this project I will identify cellular and molecular profiles of LLS in different stages of MS and determine whether these structures also develop in the visual pathway. This proposal affords me high quality training in neuropathology, neuroimmunology, molecular biology, bioinformatics, neuro-ophthalmology and the opportunity to build personal links with top international MS research centres globally. This will underpin future development of my independent research programme beyond this Fellowship and will support the resurgence of clinical MS research in Northern Ireland.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: My Day: Digital Dementia Toolkit
Funder: Economic and Social Research Council

Abstract: The aim of the My Day project is to change the experience of people living with dementia from the point of diagnosis. The majority of people live at home with dementia supported by family or friends. My Day will provide a toolkit to empower people with dementia and their families to live as well as possible whilst tracking the progress of their condition. This requires close engagement and cooperation with the NHS, particularly memory assessment clinics, to develop the pipeline for implementing My Day. This includes understanding the needs in relation to digital skills of people living with dementia, informal caregivers and NHS staff. Specific objectives and actions towards achieving this include: -Interactive workshops to gain feedback on technologies from previous projects from people living with dementia, informal caregivers, and memory clinic staff. -Using the feedback and technologies from the interactive workshops to guide co-creation of the My Day prototype, including user interface for people living with dementia and memory clinic staff. -Iterative development and testing of the My Day toolkit with NHS end users and dementia charities. -Scoping the skills and resources to build My Day as a product/service and the structures needed to deliver it to people living with dementia. -Engaging with a range of stakeholders to explore the potential of different routes to market -Create preliminary strategy for growth and sustainability. -Establish timing for creating start-up company.

Lay abstract: Dementia is a disease that attacks the brain. It mostly happens when people get older but can start when they are working age. People who develop dementia often have problems remembering things or get confused easily. There are currently no medicines to cure dementia and it gets worse over time. Most people with dementia live at home managing as best they can. Unlike illnesses such as cancer or diabetes, people who develop dementia are not given specific tools to help them cope. The My Day project will provide resources for people who are diagnosed with dementia to help them live day to day and plan for the future. Specifically, the My Day toolkit will provide information about dementia to help people understand what is happening to them. The toolkit will also provide practical strategies, and digital tools to manage their daily lives. The toolkit will run on a phone or tablet and training will be provided on how to use it. My Day is intended to help people learn about dementia and what to expect as time goes by. The toolkit will help people keep track of they are doing and share this with trusted family or friends. Collecting information over time can also help to spot early signs of change. This means more help can be put in place.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: Monitoring symptoms of Parkinson's disease to improve quality of life
Funder: Economic and Social Research Council

Abstract: 1) To innovate our current prototype of a clinical measurement device for Parkinson's disease through an iterative co-design process, that utilises input from all key stakeholders 2) To develop our current prototype of a clinical measurement device for Parkinson's disease, into a final product 3) To evaluate the final product with key stakeholders 4) To consolidate and formalise the Intellectual Property of our measurement device 5) To complete sustainability activities to continue product evaluation, research and development, and dissemination post project. - These will be driven by the findings from the current project and may include activities such as: future proofing and securing funding for ongoing development; completing ethics applications for next stage research and development; forming wider links with the NHS and other teams with technology related products already embedded within the NHS. 6) To recruit early adopters of the final product, for next stage research and development post project 7) To evaluate the project implementation

Lay abstract: Parkinson's disease affects 1% of adults over 60 years old, and due to an ageing population, its prevalence is increasing. The disease is characterised by movement symptoms and as there is currently no cure, living well with these symptoms is a priority. Movement symptoms vary during the course of a day and over the long-term, and being able to monitor these symptoms accurately and precisely has various benefits. These include informing current health status to help plan daily activities, and recording changes over time to enable optimization of treatment. We have a prototype device which accurately and precisely measures key features of upper limb movement relevant to symptoms of Parkinson's disease, while performing a short task. This project aims to develop our current prototype into a simple and easy to use home monitoring tool for people with the disease. People with Parkinson's disease, their family members, and other key stakeholders, such as clinicians and General Practitioners, will be involved in the project and product design processes. That will ensure we understand the needs of people the device will benefit, to create something meaningful to them. We will also seek their thoughts on how to re-design the prototype including its digital interface, with the aim of providing a user-friendly product and digital output that allows easy interpretation of individual results. The co-designing of the device will occur in stages so all stakeholders can have ongoing input. The overall development of the device as a home monitoring tool will be based on the information we receive. At the end of the project, we will evaluate the final product and identify early adopters ready to trial the product for home monitoring.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: Targeting the autophagy pathway in Alzheimer's disease
Funder: BRACE

Abstract: This project aimsto better understand the stages at which this mechanism is regulated and how nutrient loadcan provide a way to control it. In collaboration with Prof Alan Morgan at the University of Liverpool, we will develop a novel worm model to investigate how the level of BCAT affects protein aggregation and neurodegeneration.

Lay abstract: BACKGROUND:This project will focus on a mechanism called autophagy that has been shown to be dysregulated in a number of disease conditions including Alzheimer’s disease (AD). Under normal conditions brain cells use the autophagy mechanism for normal maintenance functions (i.e. cell survival, cell growth and in early developmentof the brain). It operates similar to our home recycling system, where some itemscan be recycled into other useful material whilst other materials that are nolongerneeded are discarded. This recycling system is increased when the cell is nutrient deprived or under some form of functional stress, both of which are conditions that the brain would be subjected to in AD. Understanding this process is therefore very important because in ADit is thought that there is a fault in this normally efficient system and thus may give rise to these conditions rather than be a consequence of them. A consequence of a faulty recycling system would be a build-up of badly recycled material in the nerve cellsor between the nerve cells, collectively termed aggregatesbut known as the tangles and plaquesthatare commonly seen in the brain of people with AD. Our group has identified a key metabolic protein called BCAT that regulates the recycling system of autophagy. Our research has already shown how BCAT protein is increased in the brains of people with AD and we now have additional evidence to support the role of this protein in regulating autophagy. AIMS: This project aimsto better understand the stages at which this mechanism is regulated and how nutrient loadcan provide a way to control it. In collaboration with Prof Alan Morgan at the University of Liverpool, we will develop a novel worm model to investigate how the level of BCAT affects protein aggregation and neurodegeneration.ANTICIPATED OUTCOMES: We will clarify and delineate the sequence of signalling mechanisms that are likely to mediatethe slow but damaging build-up of aggregates in brain cells, as they occur in AD, but as yetare still not understood. The results generated from this study will identify new and novel molecular targets, to identify where diet or new drugs could be directed for maximum to delay the onset or progression of AD to counter the ongoing lack of disease-modification interventions or long-term effective treatments.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Brainstem vagal dysfunction and recovery after critical illness.
Funder: Barts Charity

Abstract: Background: Recovery after illness requiring intensive care and/or complications after major surgery hasten death -even after leaving hospital. The reasons remain unclear, but reduced activity of a specialised nerve- called the vagus nerve- may contribute because it helps preserve organ function and ensures fitness. Hypothesis: Loss of normal vagus nerve function prevents recovery following intensive care/major surgery. Methods: Vagal function will be measured in patients by examining the regularity in heart rate before and after discharge from hospitalisation for elective surgery. Changes in vagal function will be compared with/without complications after surgery. A complementary study using a mouse model of sepsis will assess vagus nerve function, by examining the response of genes to the stress of critical illness in specific brainstem cells. Expected outcomes: 1. I will establish whether loss of vagal function persists after major surgery. 2. Genetic clues will reveal potential treatments to protect the brain/vagus nerve.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;6.4 SURGERY
Health categories: NEUROLOGICAL
Title: Improving grasp in spinal cord injury via a wearable electronic device
Funder: Spinal Research

Abstract: Finishing up the trial with participants with spinal cord injury. The data then needs to be analysed and written up. This is essentially an original objective, although the trial had to be adjusted in length and scope to be able to finish in time.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: NEUROLOGICAL
Title: Development of epidural electrical stimulation for bladder control: animal model
Funder: Spinal Research

Abstract: Effective treatment for bladder control following spinal cord injuries (SCI) has eluded clinical science. Epidural electrical stimulation (ES) of the spinal cord has been shown to effectively facilitate recovery of motor function in both animals and humans with severe SCI. In the human studies, qualitative data reviewed recovery of bladder, bowel and sexual function. In this project we aim to develop specific instrumentation and a rehabilitation paradigm using ES of the lumbar cord. We will develop a new “training” catheter that can be used in rodent studies which will enable filling/emptying of the bladder and at the same time recording bladder wall pressure and external urethral sphincter activity. We will use this catheter to systematically train the bladder to regain both filling and emptying control by increasing spinal cord activity at specific locations and periods within the filling/emptying cycles. We aim to be able to develop a protocol that can be safely translated to clinical use.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: NEUROLOGICAL
Title: Public involvement in childhood neurodisability research: moving up a gear.
Funder: Wellcome Trust

Abstract: Research in childhood Acquired Brain Injury (ABI) and neurodisability is lacking. As the major provider of paediatric neurorehabilitation, The Children’s Trust is well positioned to empower young people and families to be involved in health research, using their lived experience to shape the future neurodisability research agenda and use health research for their benefit. Specifically, the project will increase public engagement and involvement by working alongside children and families to co-produce 80% of our research projects by 2023. It aims to: &bull; Build a co-production model which engages and empowers involvement in research by parents and children with brain injury. &bull; Improve connectivity using locally inspired and driven approaches to neurodisability and brain injury research. &bull; Reach a broader public audience by bridging the knowledge gap and making research more accessible to more people. Families have demonstrated an appetite to engage in and influence each step of the research process. Through these activities they will feel empowered and connected to the research agenda. This creative and adaptive approach will encourage shared decision making by building confidence and increasing knowledge. In turn, families will advocate more confidently for improved practice and make the most of their lives.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: NEUROLOGICAL
Title: Using visual dysfunction to understand dementia in Parkinson's disease
Funder: Wellcome Trust

Abstract: Dementia is common in Parkinson’s, being six times more likely in Parkinson’s patients than in the general population. Despite this, those working in the Parkinson’s community avoid using the word or having discussions about dementia due to worries about adverse responses from patients. While a difficult conversation, new tools are needed to create awareness and open dialogue, so that we can better help patients and involve them in research and treatment targeted at dementia in Parkinson’s.As a clinician investigating mechanisms of dementia in Parkinson’s, I struggle to navigate these difficult topics with patients, and the wider public. Dementia can feel like a new trauma for patients who have just become accustomed to living with Parkinson’s. However, I need to talk about cognitive decline in Parkinson’s to engage patients in the research. In clinic, early conversations about Parkinson’s dementia can help patients gain access to appropriate support, prepare for the future, and benefit from treatments to slow progression of dementia in Parkinson’s.Therefore this project will: 1. Identify roots and triggers of discomfort linked with the concept of dementia within the Parkinson’s community 2. Co-produce information resources to support dialogue and awareness including: (i) a clinical tool to enable discussion of dementia between professionals and people with Parkinson’s, (ii) a hub of accessible, non-threatening information for people with Parkinson’s to learn about their risks 3. Embed toolkits in Parkinson’s UK’s resource packages and run a campaign to raise awareness of the risk of dementia and the toolkits.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: PD Frontline
Funder: Cure Parkinson's

Abstract: PD frontline is a component of the Remote assessment of Parkinsonism supporting ongoing development of interventions (RAPSODI) study. This is a prospective cohort study of GBA mutation carriers with PD, assessing for prodromal PD features (cognition, smell, depression/anxiety, REM sleep behaviour disorder) via an internet portal and through the post. In the long term it is hoped it will become a platform for stratification of PD risk amongst GBA carriers, allowing targeting of neuroprotective agents to high risk individuals. Some 10% of UK PD cases carry a GBA mutation and up to a further 7% carry GBA variants (such as E326K) which are PD risk factors. PD frontline aims to screen PD patients for GBA using full gene (introns and exons) sequencing. If eligible, GBA positive PD cases will be: 1) Approached to participate in the ASPro-PD trial (AS03) and other GBA PD clinical trials 2) Asked to participate in the main Rapsodi study (so that their non PD kindred can be enrolled), 3) Asked to participate in observational studies relating to GBA PD GBA negative PD cases will be: 1) Asked to participate in the ASPro-PD trial (AS03) as non GBA participants and other drug trials that do not target the GBA pathway and therefore specify GBA mutations as an exclusion criteria. 2) If they have a familial history will be referred to other studies looking at known genes or novel loci for PD risk. 3) Asked to participate in observational studies relating to PD

Lay abstract: PD Frontline has one simple aim – to identify a large cohort of subjects with genetic forms of Parkinson’s so that they can be directed to the studies that are right for them, be that other genetic studies such as RAPSODI, familial genetic studies or clinical trials. PD Frontline initially aimed to recruit 1,000 people with idiopathic Parkinson’s. It is necessary to identify sufficient numbers of new and existing cases for clinical trials of potentially disease modifying agents in PD. Importantly, should new drugs prove effective in specific gene mutation groups in Parkinson’s, it will be important for individuals to know their genetic status to obtain the best therapy.

Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: NEUROLOGICAL
Title: Experimental analysis of a genetic modifier of ALS/FTD
Funder: Alzheimer's Research UK

Abstract: A mistake in the C9orf72 gene is the most common cause of familial frontotemporal dementia. Finding out how this gene kills nerve cells should therefore tell us a lot about causes of dementia. We recently used fruit flies to show that the C9orf72 mistake results in the manufacture of two very toxic proteins. These toxic proteins cause the death of nerve cells. We will build on these exciting findings, working with both fruit flies and nerve cells from people with the C9orf72 mistake, which we can grow in the laboratory. We recently discovered that a gene called 'bowl' can make fruit flies with the C9orf72 mistake significantly better. We will use state-of-the–art genetic, computing and microscopy techniques and innovative methods to determine how bowl is combatting the C9orf72 mistake. We will do this in both fruit flies and human neurons with the C9orf72 mistake. This project and the scientific environment for the student will provide an ideal training in dementia research. The student will find the most important factors that prevent nerve cells from dying, leading to specific therapies to protect nerve cells for the toxic proteins.

Lay abstract: A mistake in the C9orf72 gene is the most common cause of familial frontotemporal dementia. Finding out how this gene kills nerve cells should therefore tell us a lot about causes of dementia. We recently used fruit flies to show that the C9orf72 mistake results in the manufacture of two very toxic proteins. These toxic proteins cause the death of nerve cells. We will build on these exciting findings, working with both fruit flies and nerve cells from people with the C9orf72 mistake, which we can grow in the laboratory. We recently discovered that a gene called 'bowl' can make fruit flies with the C9orf72 mistake significantly better. We will use state-of-the–art genetic, computing and microscopy techniques and innovative methods to determine how bowl is combatting the C9orf72 mistake. We will do this in both fruit flies and human neurons with the C9orf72 mistake. This project and the scientific environment for the student will provide an ideal training in dementia research. The student will find the most important factors that prevent nerve cells from dying, leading to specific therapies to protect nerve cells for the toxic proteins.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL