
Confidence for Translation (C4T) Awardees 2024
In 2024, Translation Manchester run the Confidence for Translation (C4T) Translation Manchester Accelerator Awards (TMAA) call, funded by the UKRI MRC Impact Accelerator Account (2022-26)
The call was extremely competitive with a great number of high quality proposals received for consideration. After thorough peer review the following proposals were funded through the C4T Scheme:
The following projects were funded through the Institutional UKRI MRC Impact Accelerator Account (IAA) (2022-2026)
Prof Adrian Parry-Jones
DIAGnosis using NOvel technology for Subtypes In Stroke (DIAGNOSIS study)
Prof Andrew King
Interleukin-1 in Vestibular Schwannoma (IL-VS): A biomarker development study
Dr Anja Wittkowski
The feasibility of translating an online psychosocial-parenting intervention into a perinatal mental health service for mothers of infants
Dr Ayodele Sasegbon
Cerebellar Metaplasticity in the Swallowing Motor System
Dr Francesco Galli
A new strategy to treat dilated cardiomyopathies with stem cells and biomaterials
Dr Hala Shokr
Dynamic retinal vascular analysis to unlock the pathophysiology and facilitate early detection of Fibromuscular Dysplasia
Dr Jose Ricardo Aguilar Cosme
Development of a capacitive electrical stimulation dental device
Dr Kate Allsopp
Enhancing patient benefit and translatability of Trauma Focused Cognitive Behavioural therapy for people at ultra high risk for psychosis
Dr Ketan Parmar
Is the ‘Easy Eyecare Pathway’ autism- informed?
Prof. Paul Mativenga
Co-Culture of S. epidermidis and MG63 Cells on Laser Engineered Implant Surfaces
Dr Penny Lewis
Integration of Patient Safety Software into Pharmacy Systems
Dr Rebecca Bromley
Investigating multigenerational risk following in utero exposure to antiseizure medications
A lay summary for each project can be found below:
Prof Adrian Parry-Jones
DIAGnosis using NOvel technology for Subtypes In Stroke (DIAGNOSIS study)
“Stroke caused by bleeding in the brain is known as intracerebral haemorrhage, or ICH for short. ICH is a major cause of death and disability. When ICH patients are in the ambulance on their way to hospital, it may be a vital opportunity to start treatments to prevent further bleeding. Reversing blood thinners and rapid blood pressure lowering are two treatments that we deliver in hospital. Treatment in the ambulance may make them even more effective. However, we currently have no accurate and cost-effective way to tell which patients have an ICH and which have an ischaemic stroke, where a blood clot has blocked an artery.
We have shown [neurologyopen.bmj.com] that simple clinical features such as high blood pressure can be used to identify ICH, but this approach only picks up around half of cases. Therefore, new technologies are needed to improve diagnosis. Our ‘DIAGNOSIS’ study aims to develop an accurate, quick, pragmatic, and cost-effective tool to identify intracerebral haemorrhage in the ambulance. We will recruit up to 300 suspected stroke patients as they arrive in the Emergency Department. We will collect clinical features and test for a marker called GFAP on a rapid lateral flow test. We will combine this test with clinical features to see if they are accurate enough when combined. If so, we aim to then move on to testing accuracy in the ambulance in a future study.”
Prof Andrew King
Interleukin-1 in Vestibular Schwannoma (IL-VS): A biomarker development study
In vestibular schwannoma (VS), inflammation is associated with tumour growth and studies have shown that one chemical mediator of inflammation called interleukin-1 (IL-1) is increased in patients with growing VS. Targeting IL-1 through drugs such as Anakinra (Kineret ©) could reduce inflammation and growth in these tumours. The first step and this study aim though is to understand the best tests or biomarkers that can evaluate whether targeting Il-1 is having an effect within VS.
For this study, ten patients due to undergo surgery for a growing sporadic or NF2-related Schwannomatosis VS at Salford Royal Hospital will be recruited. Participants will first undergo a research MRI scan for evaluation of tumour imaging biomarkers. Blood samples will also be collected so that levels of circulating pro-inflammatory chemicals (cytokines) can be evaluated. Following these tests, participants will receive a once-daily subcutaneous dose of an established, safe IL-1 targeting drug called Anakinra (Kineret ©). This drug will be given for 14 days at home by a trained member of the research team, and at the end participants will then undergo the same MRI scan and blood tests described above so that changes can be measured. During planned surgery, excess tissue from the tumour (VS) will be taken and specialised tests used to look for changes in the expression of inflammation related genes and changes in the number of inflammatory cells. To better understand how well these imaging, blood and tissue tests can detect the effects of IL-1 targeting, a separate group of 10 patients with growing sporadic VS listed who are due to undergo surgery will also be enrolled. This group of patients will not receive anakinra but will undergo the same tests detailed above, with MRI imaging and blood collection at day 0 and day 14, and analysis of resected tumour tissue.
Dr Anja Wittkowski
The feasibility of translating an online psychosocial-parenting intervention into a perinatal mental health service for mothers of infants
During the perinatal period up to 27% of new mothers experience significant mental health problems impacting their own wellbeing and their relationship with their baby. Whilst perinatal specialist mental health services exist to support these mothers, not all mothers will be accepted into the service and then offered individual or group-based psychological therapy. When they are offered therapy, mothers may have to wait before it starts depending on service capacity.
Parenting interventions were developed to improve parenting competence and confidence, improve parental wellbeing and mood and strengthen the couple relationship. Increasingly, they are delivered in a self-paced, interactive format that parents can access easily on their smartphone when, where and how it suits them. With an increasing need for digital solutions to mental health problems, we plan to test the online Triple P for Baby parenting programme (Online BabyTP). In this uncontrolled, feasibility and acceptability study, we aim to answer four key questions:
- Can we recruit these mothers?
- Will they engage with the online intervention?
- What factors helped or hindered their engagement?
- What do mothers and staff think of this intervention and its possible place as an additional intervention in this service?
We plan to recruit a minimum of 20 mothers from the perinatal specialist service in Greater Manchester, but we can offer the intervention to up to 100 mothers. Eligible mothers will be asked to complete five brief questionnaires before being offered the intervention and 10 weeks after starting it. We will offer them text messages and four calls to support their engagement and answer questions. We also plan to interview a) 10-20 mothers about their experiences with the intervention and any potential benefits or drawbacks and b) 5-10 staff about their views and any implementation issues. Feasibility and acceptability data will be analysed and reported.
Dr Ayodele Sasegbon
Cerebellar Metaplasticity in the Swallowing Motor System
Swallowing problems are common and can lead to increased hospital admissions and even death. Current treatments for swallowing problems involve altering the consistency of food and fluids. However, these treatments are not strongly supported by high-quality evidence. Repetitive transcranial magnetic stimulation (rTMS) is a technique which uses electromagnets to change the activity within specific regions of the brain. When it is used to stimulate the swallowing areas of the brain, it can improve swallowing function. This technique has been shown to improve swallowing function in people who have had strokes.
Unfortunately, not everyone experiences the benefits of this technique with some showing a greater increase in swallowing brain activity and swallowing recovery than others. This variability is due to individual differences in peoples brains and is a problem as it reduces the overall effectiveness of rTMS. A technique called metaplasticity, where the brain is stimulated twice instead of just once has been shown to improve the effectiveness of rTMS. We aim to use the technique of metaplasticity over the cerebellum (the area of the brain at the back of the head) to improve the proportion of people who gain benefit from rTMS. This study will initially be performed in healthy participants.
Dr Francesco Galli
A new strategy to treat dilated cardiomyopathies with stem cells and biomaterials
Dilated cardiomyopathy (DC) is a major cause of heart failure, often requiring heart transplantation due to the lack of effective treatments. Similarly, Duchenne Muscular Dystrophy (DMD) frequently leads to DC, but current strategies to treat skeletal muscle damage face challenges when applied to the heart. To address this, we aim to transform mesoangioblasts (Mabs) — a type of stem cell — into heart cells (cardiomyocytes) using gene therapy. By transiently activating specific genes (Gata4, Mef2c, and Tbx5), we can prepare Mabs for delivery while retaining their ability to home to inflamed, damaged heart tissue. Our innovative approach involves implanting these gene-modified cells on biodegradable nanofiber membranes beneath the skin. These membranes allow blood vessels to grow into them, enabling the cells to enter the bloodstream and travel to the heart. This method, already used in clinical materials, offers a promising system for systemic delivery. We seek funding to refine this approach, optimize cell dosing and timing, and evaluate its potential to repair heart damage in preclinical models, ultimately aiming to develop a new treatment for DC and DMD.
Dr Hala Shokr
Dynamic retinal vascular analysis to unlock the pathophysiology and facilitate early detection of Fibromuscular Dysplasia
Fibromuscular Dysplasia (FMD) is a rare vascular condition that predominantly affects younger to middle-aged women. It involves abnormalities in medium-sized arteries and is not caused by clogged arteries or inflammation. Interestingly, although FMD is less common in men, when it does occur, it tends to present in a more severe form. Historically, FMD was considered clinically insignificant and thus overlooked in UK-based research. However, recent findings show an incidental discovery prevalence of 4.4–5.8%. Notably, two-thirds of FMD patients exhibit involvement of multiple vessels, with complications ranging from severe hypertension to stroke.
Management of FMD-related complications often requires invasive procedures, which carry significant risks, including serious health problems, psychological stress, and even death. Additionally, a major challenge in the diagnosis and treatment of FMD lies in its frequent misdiagnosis or delayed identification which makes it difficult to predict disease progression or develop preventative strategies.
Recently, experts have hypothesized that FMD may not be limited to isolated vascular beds but could affect the entire vascular system. Despite this, most research to date has focused on medium-sized arteries, primarily examining blood flow and structural abnormalities. This narrow focus has limited our understanding of the disease’s systemic impact and its variability among patients.
It is well known that small vessels can reflect the global health of the vascular system. However, it’s hard to study small vessels directly because they’re so tiny and different from person to person. An exception to this is the back of the eyes (the retina).
Based on this information, our research team has developed a method to indirectly evaluate small vessels through the retina in the eye. Using a specialized camera known as a dynamic retinal analyzer (dRVA), we can now examine both the structure and function of these vessels. This approach, a completely new area that offers direct and non-invasive evaluation of the micro-vessels and holds significant promise for advancing our understanding of the disease, vascular function and complications throughout the body in FMD patients.
Our research will provide a new way to check the small blood vessels in FMD patients without needing to do invasive procedures like taking tissue samples or injecting contrast dye.
Dr Jose Ricardo Aguilar Cosme
Development of a capacitive electrical stimulation dental device
Inflammation itself is a part of normal wound healing – typically subsiding as healing progresses. Chronic inflammation can impair the normal healing process and lead to delayed or non-healing wounds. It is often associated with conditions like diabetic ulcers and pressure sores, where prolonged inflammation disrupts tissue repair and regeneration. Capacitive electrical stimulation (CES) is an innovative technique that uses controlled electric fields to stimulate tissue healing. The human body experiences these electric fields naturally, functioning part of an intricate cellular communication network that coordinates complex repair processes.
We aim to harness CES to improve wound healing, focusing on improving healing under inflammatory (disease-like) conditions. The precise control over the transition between a pro-inflammatory state to a more regenerative state, would enable us to promote new tissue growth, prevent existing tissue loss, and induce faster healing. This work has potential applications in orthopaedic and reconstructive surgeries, representing a significant step toward improving long-term outcomes for vulnerable patients requiring surgical interventions.
Dr Kate Allsopp
Enhancing patient benefit and translatability of Trauma Focused Cognitive Behavioural therapy for people at ultra high risk for psychosis
Research has shown that going through trauma and difficult life experiences affects how likely people are to develop psychosis. We have evidence-based assessments that can identify people who are at higher risk before they go on to develop psychosis, but we currently don’t have psychological interventions for trauma that are tailored for people who are at high risk of developing psychosis. It is possible that by offering trauma focussed psychological interventions that are specific and target the processes that may lead someone to develop psychosis, we can reduce both trauma related problems, and the risk of developing psychosis in the future.
Currently in Manchester, the world’s largest research study on trauma focussed therapies for people at high risk of psychosis is taking place (RESTART feasibility clinical trial). This study is gathering information on how trauma focussed therapies may work or should be adapted for this group of people. This study is testing out established trauma therapies; one of which is Trauma Focussed Cognitive Behavioural Therapy (TF-CBT).
The funding from Translation Manchester will be used to look at the information this study is gathering on TF-CBT in detail, write a manual for how best to deliver the TF-CBT therapy, and develop training materials for clinicians who work with people at high risk of developing psychosis. This work will allow us to test the therapy more fully in the future and will speed up the time it takes to get this therapy into clinical practice for NHS service users.
Dr Ketan Parmar
Is the ‘Easy Eyecare Pathway’ autism- informed?
About 1 in 70 people are autistic in the UK, and most do not have a learning disability. Autistic people seem more likely to need spectacles and develop eye conditions (e.g., problems with eye coordination or a lazy eye), and these could contribute to their visual sensory experiences. Therefore, it is important that they regularly go for eye examinations. However, our research has found autistic people may avoid going for eye examinations because they are not very accessible or “autism-informed”. This needs attention as autistic people may be missing out on important treatment (such as correct spectacles and eye exercises) and instead investing in unregulated management options.
In 2012, an accessible eyecare pathway for people with learning disabilities was introduced aiming to reduce the large number of eye conditions in this population. In 2020, autistic people were “added on” to the pathway without any supporting evidence for this being beneficial. We don’t know if:
- autistic people are aware of and using the pathway
- the pathway is autism-informed and truly accessible
- eyecare providers accredited to provide the pathway understand the differences in needs between people with learning disability and autism.
In this study, we will work with autistic people to investigate their experiences of the pathway and if they think it is autism-informed. We will also conduct focus groups with eyecare providers to explore how knowledgeable and prepared they feel to see autistic patients on the pathway. Finally, we will analyse pathway data to understand its provision and uptake. Our ultimate aim is to produce a report on the suitability of the pathway for autistic people without learning disabilities.
Prof. Paul Mativenga
Co-Culture of S. epidermidis and MG63 Cells on Laser Engineered Implant Surfaces
In 2019, there were an estimated 178 million new bone fractures worldwide, affecting 2.3% of the global population—a significant 33% increase since 1990, including 2.3 million in the UK (3.4% of the population). These injuries had a profound impact on quality of life, contributing to nearly 25.8 million years lived with disability globally, a sharp rise of over 65% since 1990. In response to this growing issue, the market for products designed to fix fractures is expanding rapidly, with projections indicating it could reach $15.2 billion by 2029, growing at a rate of 6.1% annually. Despite advancements in bone implants and treatments, complications during recovery; primarily insufficient bone to implant integration and implant infections remain a significant challenge. This highlights the need for continued innovation in fracture care and implant technology to better address patient needs.
Infections are a significant healthcare issue in Europe, with approximately 3.2 million cases diagnosed each year. These infections result in about 37,000 deaths annually and place a heavy burden on healthcare systems. They account for an additional 16 million hospital days and cost roughly €7 billion every year.
Infections related to implants are a serious complication, leading to high social and economic costs. They are typically treated with antibiotics, but with antibiotic resistance projected to cause 10 million deaths annually by 2050, alternative solutions are urgently needed. In orthopaedic trauma, infection rates can be as high as 30%, and about 80% of open fractures show bacterial contamination. These infections impact recovery significantly—young patients often struggle to return to work within a year, while older patients face an increased risk of death.
Initial testing of bone cells and bacteria typically examines their attachment to implants separately, which doesn’t fully represent the complexity of how they interact in the body. Upon implanting an orthopaedic device, a “race for the surface” occurs between the bone cells and bacteria to adhere to the implant. If bacteria succeed in colonizing the implant and forming a biofilm, this can lead to device failure.
In vivo studies, which are the best way to replicate the conditions of an actual implant, are expensive and time-consuming. To gain crucial insights into the interactions between bone cells and bacteria at the implant surface, in vitro co-culture models are a promising alternative. These models offer valuable data that can guide the development of new implants, helping to reduce the need for extensive animal testing and facilitating more effective clinical trials.
In this project, the competition between bone cells and bacteria to integrate to the surface will be observed in two different co-culture models. We hypothesise that our novel surface has an antibacterial effect with no negative effects on the bone cells. The attachment, shape, and growth of bone cells on the implant surface will be examined. Additionally, the ability of the implant to prevent the formation of bacterial biofilms will be tested.
Dr Penny Lewis
Integration of Patient Safety Software into Pharmacy Systems
INTRODUCTION: Around 3.3% people with sight impairments (PwSI) are at higher risk of medication errors, due to difficulties differentiating between medications, accessing dosage and safety instructions. By 2032, RNIB predict there will be 3.8% PwSI due to population ageing, complicated by more long-term conditions requiring additional medications, increasing the opportunities for errors.
OUR SOLUTION: Previous co-design workshops with PwSI and community pharmacists (CPs) showed CPs had no failsafe way to identify PwSI, as information about sight impairments was not available. In response we created FLAG-Me Vision, an automated system that helps pharmacists identify PwSI by displaying the highly visible ‘shaded eye logo’ on the patients’ pharmacy medication record. This will prompt CPs to offer 1:1 consultations, tailored to patient need, supported by our online resources. In the UK, there are no similar solutions, and CPs tend to rely on seeing a guide dog, person with a long cane (white stick) or dark glasses, or recognising medication specific to eye conditions (eg. Glaucoma drops).
C4T AWARD: FLAG-Me Vision was successfully tested using HospitalRun™ pharmacy software and found 35,000 PwSI when anonymised NHS records in Greater Manchester were searched. C4T will fund our work with a commercial pharmacy software supplier, to allow it to link to their software and test how it is used in one pharmacy supported by Community Pharmacy Greater Manchester. We will also collect data on delivering and costing running the identification and consultation of PwSI as a potential pharmacy service. This step is critical before we can attract funding for a study in ten pilot pharmacy sites in Spring/Summer 2025.
Dr Rebecca Bromley
Investigating multigenerational risk following in utero exposure to antiseizure medications
Antiseizure medications (ASMs), vital for treating epilepsy, can negatively affect fetal development when used during pregnancy. For example, sodium valproate has been linked to significant risks of birth defects and neurodevelopmental disorders, with possible later impacts on the next generation recently suggested by animal studies. While risks during childhood are documented, long-term health and neurodevelopmental outcomes into adulthood, as well as potential effects on subsequent generations, are poorly understood.
The project aims to establish a “research-ready” cohort by revitalizing an existing dormant UK database of over 10,000 mother-offspring pairs previously studied for ASM exposure. The cohort will include participants exposed to valproate and other high-risk ASMs during pregnancy who are now reaching adulthood. By recontacting and reconsenting participants, researchers will gather detailed health and neurodevelopmental data from adolescents and adults, and where applicable, their children. This will facilitate future research into multi- and transgenerational effects.
This research will provide critical insights into the long-term and multi-generational impacts of in utero exposure to ASMs. It will guide safer prescribing practices, enhance patient counseling, and shape health policy and healthcare interventions, ultimately improving outcomes women with epilepsy and their families.
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