The Confidence for Translation (C4T) Translation Manchester Accelerator Awards (TMAA) funded by the UKRI MRC Impact Accelerator Account (2022-26), have announced the successful applicants.  The call was extremely competitive with a great number of high quality proposals received for consideration. Below is a summary of our successful Centre-related projects.

Professor 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.

Professor 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 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 Shokr is part of Microvascular Research Group at The University of Manchester working with colleagues in our stroke and dementia theme.

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 Ayodele is part of the Centre’s stroke and dementia theme and the Manchester Dysphagia Group. 

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