NIHRDataInsights/HRCSData huggingface dataset:
Title: MICA: Delivering gene silencing therapy to the epidermis and ocular surface
Funder: Medical Research Council

Abstract: This programme is aimed at developing therapy for dominantly inherited keratinizing disorders. This group of hereditary disorders mainly causes cell fragility in specific differentiated cell compartments of the epidermis but some also affect some epithelial barrier tissues, such as the anterior corneal epithelium. Keratinizing disorders are collectively rare but when grouped together, affect about 1 in 5000 people or about 12,000 individuals in the UK alone. These conditions result in lifelong, very painful, skin blistering and thickening. The prototypic disease is epidermolysis bullosa simplex (EBS), an autosomal dominant skin blistering disorder, with 5000 cases in the UK. In Meesmann epithelial corneal dystrophy, the corneal epithelium is affected instead, leading to visual impairment and eye pain. The underlying problem in this group of conditions is dominant-negative interference resulting from missense or small in-frame insertion/deletion mutations in keratin intermediate filament proteins or related proteins. Here, we will develop a highly specialised type antisense oligonucleotide (or ASO) that can inhibit the mutant allele, without altering the normal allele. A major hurdle to applying this technology clinically is that ASOs are difficult to deliver in vivo. A US-based company, Wave Life Sciences, has recently developed a new form of ASO chemistry which is more potent, has single-nucleotide specificity and shows enhanced bioavailability The Dundee group has developed a a whole range of bioluminescent animal models expressing luciferase in specific epithelial and epidermal compartments to test ASO delivery. We have also recently developed a proprietary system for longer term and much more functional organ culture of mammalian skin. In addition to developing ASO delivery, we will build case collections of well genotyped and phenotyped patients in readiness for future clinical trials of our ASO technology or other therapeutic approaches.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: SKIN;EYE
Title: Antimicrobial paint-on bandages for Digital Dermatitis
Funder: Innovate UK

Abstract: Bandages have two primary roles: firstly, they cover a wound to stop it getting dirty and infected and secondly they allow any ointments or other applied treatments to be 'locked in', so that they don't get rubbed off and can have their effect where needed. However, bandages do not do well in the wet- such as the bath, the shower or just outside in the rain. They generally should not touch the wound directly but, instead, a sterile dressing is used and all of this is time consuming to take off and replace, on a regular basis, as the wound heals. Our company, NoBACZ Healthcare Ltd, has developed liquids that can be painted or squeezed directly onto wounds where they rapidly set, forming robust barriers that naturally degrade and shed over time and can be re-applied as required. These paint-on bandages do very well in the wet as they repel water, do not need an under dressing and are designed to repel bacteria. They could be used for any trauma wounds or surgical wounds in humans or animals, but we have identified a particularly unmet need in a disease of dairy cattle, called 'digital dermatitis'. Here, cattle get painful ulcers on their feet, which are infected with slurry-dwelling bacteria, and these are terribly hard to treat. The cost to the farming industry in the UK alone is about £60 million per annum. Worldwide it is well over a billion pounds per annum. In a small study at the University of Cambridge farm, we showed that these liquid bandages adhere well to digital dermatitis wounds, have no obvious adverse effects, promote healing and overcome associated lameness one week after a single application. We now plan to show in a large farm trial that there is a convincing case on the grounds of treatment effectiveness, animal welfare and economics for the adoption of our liquid bandages by the dairy farming community, worldwide, for the management of digital dermatitis.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: SKIN;INFECTION
Title: How does wound inflammation impact on other cell lineages at the repair site – in vitro and live imaging studies in zebrafish
Funder: Wellcome Trust

Abstract: Wound healing is the process by which skin integrity is restored following injury. At any site of tissue damage, the body activates a complex series of events to heal the wound. Each stage is necessary for effective tissue repair. Inflammation has evolved to prevent infection by pathogens. Besides killing bacteria, signals from inflammatory cells also coordinate other aspects of wound healing. However, these signals may also have negative consequences such a scarring, and if inflammation is not resolved, this can lead to chronic wounds such as diabetic foot ulcers can result. During my PhD I will investigate how inflammation impacts on three lesser studied cell types in wound healing, melanocytes (pigment cells), adipocytes (fat cells) and the cutaneous nerves in skin. It is thought these three cells could play interesting, but as yet unknown roles in wound repair, which may aid repair or be pathological. I will use live imaging in the translucent zebrafish to look at how these cells interact with inflammation, and what signals may cause this. This work could reveal the impacts of inflammation at the wound repair site, which could have impact on wound treatment in the clinic.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN;INFLAMMATORY AND IMMUNE SYSTEM
Title: Defining ‘clinically actionable’ genetic mechanisms in atopic eczema risk and resolution
Funder: Wellcome Trust

Abstract: Atopic eczema is an itchy condition characterised by skin barrier dysfunction and inflammation. It frequently causes chronic morbidity, but a subset of cases enter long-term remission, demonstrating that resolution may be a tractable therapeutic aim. Eczema is highly heritable. Null mutations in FLG are the strongest genetic risk and a locus on chr11q13.5, for which the nearest gene is EMSY, has a multiplicative effect. We have shown that EMSY is a transcriptional regulator in skin, controlling multiple aspect of barrier formation. We will investigate molecular mechanisms at these two major risk loci: chr1q21.3 (FLG, FLG-AS1 and related genes) and chr11q13.5 (EMSY and LRRC32), aiming to define pathways contributing to eczema resolution. Findings will be tested in a well-characterised birth cohort (ALSPAC), to confirm clinical relevance. Analyses of European cohorts (n>25,000) show evidence of gene-environment interactions in eczema, but these findings require validation. We will use an optimised skin organoid model to investigate three environmental factors (tobacco smoke, wash-products and pet allergens) for which there is evidence of interaction with FLG genotype. Detailed functional and biochemical phenotyping will increase understanding of gene-environment interactions. This work will inform eczema prevention strategies and characterise mechanisms contributing to eczema resolution, as future therapeutic targets.

Lay abstract: Eczema is an itchy skin condition affecting 1 in 4 children in the UK and 1 in 10 adults. It often occurs along with other allergic conditions, causing considerable suffering. Eczema is caused by a combination of genetic inheritance -coded in our DNA- and environmental factors that irritate the skin. The incidence of eczema has risen dramatically, for reasons that are unknown. Current treatments only suppress eczema, but some people do ‘grow out’ of their eczema, giving hope that a cure may be possible. Our work uses human skin cells grown in the laboratory. We have two main aims: Firstly, to understand how environmental effects (smoking, washing and pet ownership) affect skin at risk of eczema, so we may learn more about prevention. Secondly, to investigate ways in which skin can recover from eczema, in the hope that we may target these mechanisms to develop better treatments for the future.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: SKIN;INFLAMMATORY AND IMMUNE SYSTEM
Title: Using JAK inhibitors to repair the skin barrier in severe ichthyosis
Funder: LifeArc

Abstract: Autosomal recessive congenital ichthyoses (ARCIs) are rare genetic skin disorders where babies are born covered with a membrane which sheds to leave red, scaly skin all over their bodies. ARCIs are life-long disorders and reduce quality of life significantly. The most severe form of ARCI, harlequin ichthyosis (HI), is caused by a mistake in a gene called ABCA12 that transports lipid (fats) in the upper part of the skin. This defect makes the skin leaky, resulting in loss of water and protein and increased risk of infection. JAKS are proteins in a cell involved in processes such as immunity, cell division, cell death and tumour formation, which communicate via a signalling pathway. In a tissue culture model of HI, the research team found that blocking a cellular pathway known as the JAK pathway with a licenced drug called tofacitinib (a JAK pathway inhibitor), reversed the leakiness of the skin. This improved the skin barrier. As HI is a very severe skin barrier disorder, it is likely that JAK inhibitors will also work in less severe forms of ARCI if this success is confirmed. JAK inhibitors are in clinical trials for many common skin diseases, particularly atopic eczema. In this study, the team will generate models of HI and one of the other ARCI types in a tissue culture dish and treat them with five available JAK inhibitors. The team will record changes in the skin model in detail. They will profile the lipids and genes in the treated model and then pick two JAK inhibitors to use in a mouse model of HI. These data should allow the team to choose the right JAK inhibitor for treatment of patients with HI and other severe ichthyoses and improve understanding of how these drugs work in repairing the skin barrier.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: SKIN;INFLAMMATORY AND IMMUNE SYSTEM
Title: Coeliac disease and alopecia areata
Funder: Alopecia UK

Abstract: An association between alopecia areata (AA) and coeliac disease (CD) was first reported in 1995, and since then, although genetic similarities have been identified, a clinical association between these conditions remains undetermined. Furthermore, there is a lack of data pertaining to the impact of CD on micronutrient malabsorption and subsequent effect on hair cycle. We aim to explore whether an association exists between coeliac disease (CD) and alopecia areata (AA), and the impact of gluten-free diet on hair regrowth in these patients, as well as the presence of concomitant micronutrient deficiencies. We aim to conduct a large-scale, retrospective study looking at the medical notes of all paediatric patients diagnosed with alopecia areata, totalis or universalis presenting to our tertiary hair clinic over the last 20 years. Our practice has always been to perform coeliac screening for children with AA. From this we aim to determine the prevalence of concomitant AA and CD in our population, whether a diagnosis of CD was confirmed on endoscopy, a gluten free diet was established, the impact of gluten free diet on hair regrowth, micronutrient profiles at the time of diagnosis, the presence of any micronutrient deficiencies, whether replacement was initiated, and if this had an impact on hair regrowth. This study may have implications for the way we screen patients with AA for autoimmune disorders and micronutrient deficiencies. There may also be therapeutic implications through gluten-free diet, and micronutrient replacement, which have been reported to lead to hair growth in AA in specific contexts.

Lay abstract: Alopecia areata is an autoimmune condition that causes hair loss. There may be an association between AA and coeliac disease. Dr Salam will investigate this association by conducting a retrospective analysis of patient records from their hair clinic over the last 20 years. They hope this will establish if, in people with AA and coeliac disease, a gluten-free diet or correction of micronutrient deficiencies could lead to hair regrowth. This research may help establish better ways to screen patients with AA for autoimmune disorders and micronutrient deficiencies, and may identify nutritional pathways for hair regrowth in this group.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: SKIN;ORAL AND GASTROINTESTINAL
Title: A pragmatic multicentre randomised controlled trial comparing stapled haemorrhoidopexy to conventional excisional surgery for haemorrhoidal disease.
Funder: Chief Scientist Office (Scotland)

Abstract: DESIGNThe design of the study will be a pragmatic multicentre randomised controlled trial comparing stapled haemorrhoidopexy with conventional excisional haemorrhoidectomy. SETTINGFifteen colorectal surgical units from across the UK. The sites who thus far have areed to participate are: Manchester Royal Infirmary Aberdeen Royal Infirmary Northern General Hospital Sheffield Leeds Teaching Hospitals Stepping Hill Hospital Glan Clwyd Hospital Ninewells Hospital Dundee Glasgow Royal Infirmary Glasgow Southern General Hospital Whiteabbey / Antrim Area Hospital Ulster Bradford Hospitals NHS Trust Bristol NHS Trust and Taunton and Somerset NHS Trust. TARGET POPULATIONAdults aged over 18 years old for whom surgery for haemorrhoidal disease is recommended. Patients with 2nd degree haemorrhoids who have failed conventional therapy (2 episodes of rubber band ligation) 3rd and 4th degree haemorrhoids will be included. Patients who have had previous surgery for haemorrhoids (except those who have only had 2 prior episodes of rubber band ligation for grade II haemorrhoids); pre-existing sphincter injury peri-anal sepsis inflammatory bowel disease or malignant colorectal disease will be excluded.HEALTH TECHNOLOGIES BEING ASSESSEDThe interventions being compared are stapled haemorrhoidopexy (SH) with conventional excisional haemorrhoidectomy (CH). MEASUREMENTS OF COSTS AND OUTCOMESWe will assess outcomes up to two years with possibility of longer-term follow-up to 5 years through a separate funding application. Primary outcome measures: Health-related quality of life profile (area under the curve) derived from EQ-5D measurements at baseline 1-week 3-weeks 6-weeks 1-year and 2-years. Primary trial economic outcome: Incremental cost per QALY at 2-years. Primary economic model outcome: Incremental cost per QALY over the lifetime of the patient.Secondary outcome measures: Post operative complications (including: post operative haemorrhage; requirement for blood transfusion; anal stenosis; anal fissure; urinary retention; residual anal skin tags; difficult defecation; wound discharge; pelvic sepsis; and pruritis); Patient-reported post-operative analgesia consumption; Length of hospital stay; Time to recovery; Generic Health profile measured by the SF-36; Visual analogue scale (VAS) pain score; Cleveland incontinence score; Haemorrhoid symptom score; Patient reported recurrence; Costs to the patient and NHS at 2 years; Estimated lifetime cost to the NHS and patient; QALYs estimated from the EQ-5D at 2 years; QALYs estimated over the patients lifetime.


Research activity codes: 6.3 MEDICAL DEVICES;6.4 SURGERY
Health categories: SKIN;ORAL AND GASTROINTESTINAL
Title: A Phase II Simon Two-Stage Efficacy Study of Intracerebral CTX-DP in Patients with Stable Paresis of the Arm Following an Ischaemic Stroke
Funder: Innovate UK

Abstract: Disability affects approximately 50% of stroke survivors due to permanent loss of brain tissue. ReNeuron is testing the effectiveness of a unique stem cell product, called CTX, in disabled stroke patients. ReNeuron has developed CTX from human brain stem cells, with cell banks established to provide the large quantities needed for clinical use. The safety of CTX has been assessed in stroke-disabled patients in Scotland. Treatment of all patients in this Phase I clinical trial has been completed, with no reports to date of any serious side effects or worsening in disability in the patients. Sustained reductions in neurological impairment and spasticity have also been observed in most patients compared with their stable pre-treatment baseline performance. TSB support is needed to conduct a Phase II study in up to 41 patients with upper limb paralysis at 2-4 months after their strokes. This proposed clinical trial will determine if CTX produces clinically meaningful improvements in the use of the paralysed arm at 6 months post-treatment in a sufficient number of patients treated. Success in this project will represent a significant milestone for ReNeuron and for the wider stroke field.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: STROKE
Title: The development of a feasible structured upper limb exercise programme in UK stroke rehabilitation units
Funder: Department of Health (England)

Abstract: The development of a feasible arm exercise programme in UK stroke rehabilitation units Arm problems are common after stroke. Repetitive task-specific exercises have been shown to improve arm function but at present not enough exercises are being carried out in stroke rehabilitation. Alternatives to an increase in one-to-one therapy are needed to help people after stroke carry out more arm exercises. One alternative, which has been shown to work, is the Graded Repetitive Arm Supplementary Program (GRASP). This research project aims to adapt GRASP for the UK and establish if it is feasible to use this programme in NHS settings.


Research activity codes: 6.7 PHYSICAL
Health categories: STROKE
Title: Feasibility of a community based cycling exercise programme in stroke survivors.
Funder: Chief Scientist Office (Scotland)

Abstract: This project will assess the feasibility of conducting a randomised controlled trial for a community based cycling exercise programme to improve physical and psychological outcomes in stroke survivors. Stroke is the leading cause of disability in the UK. The role exercise has in improving function and preventing future ill health was placed in the top ten research priorities by stroke survivors, carers and health professionals. After discharge from in-patient care, the options for regular exercise for stroke survivors are often limited to local council funded facilities. This study will assess the feasibility (recruitment, retention, appropriateness, safety and acceptability) of a cycling based exercise intervention programme, designed to run within existing local council services, for both ambulatory and non-ambulatory stroke survivors. The appropriateness, safety and acceptability of the programme will be assessed using semi-structured interviews and focus groups and added to quantitative measures of recruitment, retention, adverse events and adherence.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: STROKE
Title: Understanding the experiences and multi- dimensional needs of people with major stroke: a mixed methods study
Funder: Chief Scientist Office (Scotland)

Abstract: The prognosis of patients with total anterior circulation (TAGS) strokes who survive to hospital discharge is as poor as many cancers, yet they are not included in palliative care registers in primary care. We will use serial qualitative interviews, with up to 30 TAGS patients (recruited from 3 sites), and their informal and health care professionals at 4-8 weeks, 6 months and 12 months after the index stroke, to describe multidimensional illness trajectories, identify unmet care needs and determine whether, and when, a palliative care approach may be appropriate. Our data linkage study of TAGS patients admitted to our stroke units (death, pattern and duration of subsequent hospital admissions) will put the qualitative data in context. If, as anticipated, we identify unmet need for palliative care, our data will inform the development and testing of an intervention to provide palliative care to stroke survivors who need it.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.2 END OF LIFE CARE
Health categories: STROKE
Title: Can an arts based creative engagement intervention following stroke improve psychosocial outcomes? A feasibility trial of a creative engagement intervention for in-patient rehabilitation.
Funder: Chief Scientist Office (Scotland)

Abstract: Stroke is the main cause of complex adult disability in Britain. Stroke rehabilitation is typically task-orientated, focusing on physical and functional independence. Psychosocial consequences of stroke are serious and mediate recovery, influencing family relationships, community reintegration and quality of life. Therefore, improving psychosocial outcomes after stroke could improve overall recovery.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: STROKE
Title: Caring for a child with type 1 diabetes: a qualitative investigation of parents’ experiences and views
Funder: Chief Scientist Office (Scotland)

Abstract: Creative arts programmes are increasingly used to address psychosocial outcomes in long-term and mental health conditions. These programmes focus on positive influences of engagement in creative art activities facilitated by artists. However there is little research into effects of creative engagement on psychosocial outcomes after stroke.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: STROKE
Title: Physical activity for non-ambulatory stroke survivors living at home: developing a feasible and acceptable intervention
Funder: Chief Scientist Office (Scotland)

Abstract: Background:Stroke guidelines recommend physical activity, however non-ambulatory stroke survivors have largely been excluded from physical activity research. Aim:Develop and evaluate the feasibility and acceptability of a physical activity intervention for non-ambulatory stroke survivors at home. Methods • Stage 1: focus groups, exploring physical activity needs, goals, barriers, motivators with 16 non-ambulatory stroke survivors and carers (two groups), 4 health care and 4 exercise professionals (one group). • Stage 2: development of an intervention in two different formats (i.e. home-based individual and community-based groups), based on stages 1-2. Stage 3: feasibility testing: 30 stroke survivors will participate in the intervention (15 in each format). Evaluation will comprise: recruitment and retention rates, adherence, safety, preliminary outcomes (personal goals, function, activity, participation, selfefficacy, mood), assessed at baseline, after the intervention and at 3-month follow-up. Preliminary exploration of within- and between-group changes will be undertaken. Focus groups will gauge participants' views.


Research activity codes: 6.7 PHYSICAL
Health categories: STROKE