NIHRDataInsights/HRCSData huggingface dataset:
Title: Ganaxolone for treating seizures caused by CDKL5 deficiency disorder in people 2 years and over [ID3988]
Funder: Department of Health and Social Care

Abstract: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a disease caused by mutations in the CDKL5 gene, which provides instructions for making proteins essential for normal brain and neuron development. The mutation results in a reduction in the amount of CDKL5 protein produced[1] . CDD is characterised by seizures and neurodevelopmental delay and can manifest in a broad range of clinical severity [2] . Often the first symptom of CDD is seizures that occur within the first few months of life with most children experiencing multiple seizures a day[3] . Other common symptoms include hypotonia, sleeping difficulties, cortical visual impairment and learning and motor disabilities[4] . The genetic cause of CDD was first identified in 2004 so data surrounding the long-term prognosis and survival is not available[5] . However, it has been reported that some adults have been diagnosed with CDD in their 40s and 50s[5] . _x000D_ _x000D_ Most CDKL5 mutations are not inherited, and instead usually occur spontaneously. Mutations are believed to occur in approximately 1 in 40,000- 60,000 live births[2] , suggesting 11-17 people are born with CDD a year in England and Wales. CDD effects four times as many females as males (the CDKL5 gene is found on the X chromosome), but males may experience a more severe disease [2] . _x000D_ _x000D_ There is currently no specific treatment or cure for CCD. Instead, early intervention with a multidisciplinary approach to manage symptoms is recommended[1] . There are several anti-seizure therapies, which can be given either as a monotherapy or in combination. Some people might also try a ketogenic diet or steroids. If people are refractory to anti-seizure therapies, they may benefit from vagus nerve stimulation or other surgical interventions._x000D_ _x000D_ References_x000D_ 1- National Organization for Rare Disorders (2020). CDKL5 Deficiency Disorder. Accessed December 2021_x000D_ 2- Jakimiec M, Paprocka J and Smigiel R (2020). CDKL5 Deficiency Disorder — A Complex Epileptic Encephalopathy. Accessed December 2021_x000D_ 3- Genetic and Rare Diseases Information Center (2021). CDKL5 deficiency disorder. Accessed December 2021 _x000D_ 4- Olson HE et al. (2019). Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review. Accessed December 2021_x000D_ 5- The International Foundation for CDKL5 Research (2021). About CDKL5. Accessed December 2021

Lay abstract: To appraise the clinical and cost effectiveness of ganaxolone within its marketing authorisation for treating seizures caused by CDKL5 deficiency disorder (CDD) in people aged 2 years and over.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL
Title: Establishing translational opportunities for implantable brain computer interfaces in the UK ecosystem
Funder: Department of Health and Social Care

Abstract: Research into Brain Computer Interface (BCI) controlled assistive devices has demonstrated incredible potential [1] [2] to improve the quality of life (QoL) of those patients with severe paralysis but intact cognition (e.g. providing: communication, rehabilitation, manipulation and locomotion) as well as increasing the self sufficiency of this group with extremely high care needs. However, the literature is dominated by non-invasive BCIs using skull-cap electrodes, that are unsuitable for routine use as they: require lengthy expert setup; produce unreliable data requiring monitored interpretation; and even with long training the speed and degree of control is extremely limited [3] [4]. Implanted BCI (iBCI), where electrodes are inserted under the skin or on/inside the brain, could offer much higher performance and enable completely new assisitive device capability, but traditional highly invasive implantation surgery has been a major barrier to adoption and translation. Recent advances in techniques for minimally invasive implantations [5] [6] and in the performance of implanted devices have opened a window of opportunity that is being supported through guidance and by regulatory reform both in the US and UK [7] [8] [9] [10]. Commercial interest and investment has subsequently rocketed, however, this is largely being exploited by US neurotechnology companies [11] and aligned with US insurance based healthcare economics, rather than overall cost of care. On the other hand, the UK boasts a cost-benefit methodology and framework set forth by the National Institute for Health and Care Excellence (NICE). A timely, open-access and peer-reviewed study into the UK healthcare economics of iBCI assistive devices could sway large quantities of research and development funding at a critical time &ndash; aligning research objectives with NHS needs and providing a firm footing for UK based companies to seek funds from the market.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: NEUROLOGICAL
Title: Development of a Quality Management System for MoveMed, a remote monitoring solution for neurological disease, to enable clinical evaluation.
Funder: Department of Health and Social Care

Abstract: Unmet Health Need: Care for most neurological disease relies on measuring movement using crude assessments with descriptive scales e.g. comparing &ldquo;a little&rdquo; versus &ldquo;a lot&rdquo; of weakness. These often differ between professionals, (especially those less experienced e.g. primary care), need in-person consultations (incompatible with virtual clinics) and may not detect important changes as they occur (e.g. treatment failure).[1] Overall, this delays access to treatment (46% Patients, Neurological Alliance) and increases disability[2-4]. Clinical practice needs a tool to provide accurate, remote disease monitoring. MoveMed: Developed by Neurosurgeons B.Davies/M.Kotter and computer scientist R.Harle at University of Cambridge, MoveMed bridges the gap to truly background monitoring by integrating on screen games through smartphones, within algorithms. This provides a quantitative readout of neurological functions such as dexterity, balance, gait and tremor. Initial testing in Degenerative Cervical Myelopathy (a spinal cord disease that affects 1 in 50 adults) [5], has shown this can provide specific metrics that correlate with current disease standards, can distinguish DCM from healthy controls, and detect clinical deterioration before existing tools. This has supported a patent application [GB2601157]. Current Status: This concept exited the University as MoveMed Ltd (movemed.io). An initial pre-seed funding (&pound;60, 000) enabled the development of a minimum viable product and arrival of A.Jenking as CTO. MoveMed now needs to undertake longitudinal studies alongside clinical care to define the measurement thresholds that are meaningful and should inform decisions, per disease indication.[6] Barrier: MoveMed is pre-regulation/certification. This makes integration with clinical studies challenging, as for example NHS research sites understandably seek significant data security assurances.[7-8] A data breach would also represent the most significant risk for MoveMed. Proposed Activity: Prepare and test a quality management system (QMS) for MoveMed, to facilitate integration with active UK clinical trials and to submit for UKCA. Project duration 6 months.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: 'Diagnostic test accuracy of remote, multidomain cognitive assessment (telephone and video call) for dementia
Funder: Department of Health and Social Care

Abstract: As a result of social distancing and other Covid-19 restrictions, dementia assessments have moved from in-person to remote testing. In the NHS, various modalities are being used including telephone, video-call and self-complete testing. However, with no guidance on the best approach there is substantial variation in practice._x000D_ _x000D_ Cognitive assessment is integral to diagnosis, follow-up and research and so the change to remote testing potentially affects tens of thousands of people across the UK. _x000D_ _x000D_ The need for an evidence base to guide clinical practice in remote testing has been recognised by the Royal College of Psychiatry and NIHR. Our group have been approached by the European Academy of Neurology to provide a review to inform proposed guidelines on remote dementia assessment. Through our links with Alzheimer’s Society we have also learned that remote testing is a major concern for people living with dementia. _x000D_ _x000D_ From initial scoping we have identified sufficient studies to allow meta-analyses at the individual test level. If data allow, we will work with NIHR CRSU to create a network that compares accuracy across tests. _x000D_ _x000D_ We have an experienced team working on these reviews, with expertise in test accuracy analyses, strong links with NIHR CRSU and lay representation.

Lay abstract: See plain English summary

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Playlist for Life: Can personalised music be rapidly implemented in care homes as a non-pharmacologicial intervention for dementia?
Funder: Chief Scientist Office, Scotland

Abstract: Many people with dementia in care settings are prescribed drugs to help with stress or distress but non-drug alternatives – like music – could be as effective. Playlist for life offers structured listening to a playlist of personally meaningful music developed after one-to-one life story work with trained “Music Detectives”. In preparation for a large trial investigating personalised music, we want to prove we can quickly compile playlists for 60 people with dementia and see how much these playlists are used. We also want to explore what people with dementia and their relatives think is the most important result to measure in the trial.


Research activity codes: 5.8 COMPLEMENTARY
Health categories: NEUROLOGICAL
Title: Single-cell transcriptomic analysis of anaesthetic effects on neuronal and non-neuronal cell populations modulating CNS vulnerability
Funder: Chief Scientist Office, Scotland

Abstract: Brain dysfunction following surgery and anaesthesia is common and can lead to significant disability. There is no treatment and the reason why it happens is poorly understood. In prior work, we found that anaesthesia alters the levels of a large number of different genes in the brain. Some of these genes are important for protecting the brain during injury. There was also an indication that these changes were not confined to nerve cells and affected other important cell-types in the brain. In this project, we want to understand how anaesthesia affects different types of cells in the brain. We will do this using a new technology that allows us to measure the levels of genes in individual cells on a cell-by-cell basis. We predict that anaesthesia will alter levels of genes across all the different types of cells found in the brain and will alter these cells into a way that drives enhanced brain vulnerability. As anaesthetic agents work by reducing the firing of nerve-cells in the brain, we also want to see whether increasing the firing of nerve-cells in vulnerable brain areas can reverse these changes. This will be done using a new method of stimulating the brain from outside the skull by applying overlapping electrical fields. This will help us understand to what extent the changes caused by anaesthesia are reversible and potentially indicate a new treatment method that could protect vulnerable patients


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL
Title: Precision-MS: Integrating precision metrics of brain health into early treatment of multiple sclerosis
Funder: Chief Scientist Office, Scotland

Abstract: Multiple sclerosis (MS) is the leading cause of acquired neurological disability in young people, and rates of MS in some regions of Scotland are the highest in the world. Over the past decade there has been a revolution in the discovery of drugs for the treatment of multiple sclerosis. There are now at least 10 different drugs, each of varying strength. The strongest drugs are the riskiest, so choosing a drug of appropriate strength, and monitoring its effectiveness is very important. If MS is under good control then the risk of future disability is less. However, the methods used to monitor activity of MS in Scotland are imprecise and variable. More precise and accurate ways of measuring MS disease activity are needed if we are to give the right treatment at the right time, to the right person. The Precision-MS study will introduce precise measurements of brain health to people with MS, to help them make more informed treatment decisions about their disease. We aim to recruit 220 patients with newly diagnosed relapsing-remitting MS from different sites in Scotland, and generate precision measurements of MS disease activity. For example we will measure whether there has been any brain shrinkage on brain MRI scans, and will also see if we can detect brain proteins in a blood test. If brain shrinkage is detected, or brain proteins can be detected in the blood, then this can mean an increased risk of disability in the future. We will therefore make these results available to people with MS so they can make better informed decisions about treatment with their doctors. We will carefully monitor how these more precise measurements of brain health help people with MS achieve better control of their disease. We will ask whether this approach reduces future risk of disability. The ultimate aim is to make these precision tests widely available across Scotland and transform MS care. As part of the study we will build the expertise and structures to make these approaches available to all people with MS in Scotland


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: NEUROLOGICAL
Title: Bench-To-Bedside Parkinson's Disease Research: Biomarkers in LRRK2
Funder: Chief Scientist Office, Scotland

Abstract: Parkinson’s disease (PD) is a devastating neurodegenerative condition that affects over 5 million people worldwide and 12000 here in Scotland. There is no simple test for diagnosis and no cure. What is needed most are treatments that slow down or better prevent the relentless progression of disabling symptoms and underlying neurodegeneration. However, a real challenge is the complexity of the condition in terms of clinical presentation, genetics and underlying key molecular pathways. The MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) at the University of Dundee where I am based is an internationally leading research institution at the heart of the matter of dissecting cell communication mechanisms and how disruption of these processes causes PD. Although the underlying cause for PD is largely unknown (idiopathic PD), 1% of all sporadic and 2-4% of all familial cases can be explained by genetic changes or mutations in the Leucine rich repeat kinase 2 (LRRK2), which results in hyperactivation of the LRRK2 kinase. The current concept is that LRRK2 inhibitor compounds might counteract the effect of the genetic changes in LRRK2 and have potential therapeutic benefit in LRRK2-associated PD. Excitingly, LRRK2 kinase inhibitors have recently entered clinical trials. I have developed a blood test that allows measuring of the activity of the LRRK2 kinase. This has already led to very exciting new discoveries including the finding that genetic changes in another Parkinson’s associated gene, VPS35, also result in increased LRRK2 kinase activity. During my fellowship, I will take a translational approach combing genetics, clinical and mechanistic stratification of people with sporadic and familial Parkinson’s disease to understand the role of the LRRK2 kinase in more detail and unravel novel LRRK2 network components. The hope is that this work will contribute to matching people with PD with the most appropriate emerging disease modifying treatments and identify new targets for drug development. I will also focus on the physiological role of LRRK2 during infection and the recently discovered link between LRRK2 and inflammatory bowel disease.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Pre-Clinical Validation of Clinical Grade Human Olfactory Mucosal-Derived Mesenchymal Stem Cells.
Funder: Chief Scientist Office, Scotland

Abstract: Spinal cord injury (SCI) can have devastating effects resulting in loss of nerve function and patient paralysis. There are currently no treatments to help patients restore function after SCI, however, cell transplantation where damaged tissue is replaced with healthy cells is a promising strategy. Many types of cells have been studied for transplantation, but we are focussing on cells from nose tissue, known as olfactory tissue. The olfactory system is of interest for regenerative medicine as it continually supports new nerve growth throughout life due to unique cells that reside in the tissue. Using cells generated from human olfactory mucosa (OM) biopsies, we have identified a novel stem-like cell that promotes myelination and neurite outgrowth in rat models of central nervous system injury both in a culture dish and in animal models. In this study, we aim to demonstrate that clinical grade cells can be generated with the same therapeutic properties as lab based cells with the aim to produce a protocol to support a subsequent clinical trial application to grant funders.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: NEUROLOGICAL
Title: Clinical translation of an automated brain MRI health index to predict dementia
Funder: Chief Scientist Office, Scotland

Abstract: One in three people born in the UK today will develop dementia. Predicting who will develop dementia is challenging. MRI scans can detect markers of small vessel disease and brain shrinkage which may herald the earliest signs of dementia. However, these markers on their own have only a limited ability to identify who will develop dementia. We have therefore created a method for capturing all of these markers in a single measure – the ‘brain health index’ (BHI). Initial work suggests that BHI is a better measure of dementia risk than individual brain MRI markers. We have tested BHI in small numbers of people with stroke; we now want to see if the approach works in wider patient groups. We will use scans obtained from people with varying degrees of memory problems that attended research studies, clinics and hospitals in the UK and Europe. We believe that using existing scans is the most cost-effective and efficient way to thoroughly test BHI. We will involve clinicians and the pubic at all stages of our project. Our goal is to assess whether BHI provides useful information on risk of dementia for clinicians, patients, and researchers designing studies of potential treatments.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Early detection of Alzheimer’s disease with glucoCEST MRI: a proof of concept study
Funder: Chief Scientist Office, Scotland

Abstract: Alzheimer’s disease (AD) is the most common type of dementia. Patients experience increasing problems with memory, speaking, thinking, and other activities of daily living. Most available treatments aim at controlling symptoms at early stage rather than providing a cure. Therefore, early diagnosis of AD is important. A strong indicator of AD is the low ability of brain cells to use glucose. Currently, the low concentration of glucose in a brain with AD can be measured by injecting radioactive glucose and imaging the brain with positron emission tomography (PET). However, PET both exposes patients to ionising radiation and is expensive for routine use to diagnose AD. A recently developed method, called Chemical Exchange Saturation Transfer (CEST), can image brain glucose using magnetic resonance imaging (MRI). MRI has no radiation exposure risk to patients. We will study, for the first time, if CEST can detect differences in glucose concentration between patients with AD and normal volunteers of similar age. This study will set the foundation for future research to examine the clinical utility of this method for detecting AD very early. MRI is safe, less costly and more widely available, therefore CEST MRI has the potential to replace PET for assessing brain glucose in patients with AD symptoms or screening those genetically at risk.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: A window in the brain 2: Novel quantitative seizure detection tool for paediatric critical care. A multi-centre feasibility study.
Funder: Chief Scientist Office, Scotland

Abstract: Fits (seizures) are common in critically-ill children and affect how their brains recover from illness. Knowing if or when fits happen allows doctors and nurses to treat a fit early and can improve the patients’ outcome. Detecting fits in intensive care units (ICU) is very difficult. It requires experts to collect brainwave recordings (EEG) and specialist doctors to review these recordings to see if the patient is having a fit. The collection, recording and review of the recordings cannot be provided at all times. We aim to give ICU doctors and nurses an easy-to-use and accurate fit detection tool that does not require an expert doctor to collect and review the recordings. We already have an innovative fit detection tool that uses computer software to analyse the brainwave recordings without needing an expert’s input. But this tool needs 8 ‘lines’ (electrodes on the head) of the brainwaves to detect fits. ICU bedside nurses and doctors can only collect 4 lines of brainwaves without experts being there. In this project, we will improve this tool’s ability to detect fits using just 4 lines of brainwaves, meaning that it can be used at any time without the need for experts. To make sure our fit detection tool works in different ICU, we will work with other hospitals across Britain to collect brainwaves recordings from children. This will let us set-up the first children’s brainwave recording database for research and help us improve the care and outcome of critically-ill children


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL