Current funder: NIHR EME

The SC IL-1 RA in Subarachnoid haemorrhage aims to test whether a drug called Kineret can improve recovery following a SAH.

This has the potential to make a profound difference to quality of life following a haemorrhagic stroke.

• Learn more about SC IL-1 RA in SAH.

Current funder: NIHR

The CHOSEN study investigates whether oral healthcare following stroke reduces the likelihood of stroke associated pneumonia (SAP).

SAP is associated with poor clinical outcomes, this study aims to look at whether different types of toothpaste and toothbrushes can reduce SAP in stroke patients, and subsequently improve clinical outcomes.

• Learn more about CHOSEN.

Previous funders: Health Foundation, Connected Health Cities
Current funders: Health Innovation Manchester, Stroke Association, Innovation Agency, Yorkshire & Humber AHSN, AHSN for the North East and North Cumbria
Local researchers: Adrian Parry-Jones, Hiren Patel, Matt Sutton, Paul Wilson, Lisa Brunton, Emma McManus, Kate Woodward-Nutt, Khalil Kawafi, Appu Suman
External researchers: Martin James (SSNAP), Karla Hemming (University of Birmingham)

The ABC-ICH project was designed to improve survival and recovery from bleeding in the brain or intracerebral haemorrhage (ICH), improving the delivery of acute care for all ICH patients using the ABC care bundle. This was implemented at Salford in 2015-16 and reduced 30-day deaths by a third, saving around 29 lives a year.

Research identified what worked well and what barriers were encountered, refining our approach for the next phase. To provide clinicians with key information at the bedside and allow simple, real-time capture of key performance indicators, we developed the clinician-facing ABC-ICH app and dashboard.

A phased scale-up of the ABC-ICH project across the north of England commenced in 2021, covering 25 hospitals and a population of around 10 million. A Stroke Association Project Grant (2021-23) will allow us to determine whether long-term disability is reduced.

Learn more about ABC-ICH:

• Can a new treatment package improve survival and life after stroke caused by a bleed in the brain? (Stroke Association)
• Scale-up of ABC care bundle for intracerebral haemorrhage across two hyperacute stroke units in one region in England (BMJ Open)
• Video: Patient story – Ann Bamford (YouTube)

We are working on a new thrombolytic or clot-busting drug called ADAMTS13, which shows promising results in animal models of stroke.

ADAMTS13 specifically targets a protein known as von Willebrand factor (VWF), which contributes to clot formation and is common in clots seen in patients with ischaemic stroke.

We have developed a variant of this protein that is constantly active – caADAMTS13 – which enables it to break down even more VWF than the native protein.

Recent research in our group has shown that caADAMTS13 is better at breaking down platelet-rich clots than the current thrombolytic drugs licensed for use in stroke patients, and may reduce the risk of bleeding associated with current treatments.

We are now working on scaling up this research to look at other types of clots in ischaemic stroke, and if caADAMTS13 can be safely given over a longer time window, which would mean more patients could be treated with it if it was eventually licensed.

Excitingly, we hope to see this drug in clinical trials within the next five years.

The illustration above shows how blood clots form, and how ADAMTS13 could break them down.

VWF is produced by endothelial cells on the inner surface of blood vessels.

Molecules of VWF attach to each other, creating long chains.

These long chains recruit platelets, which become activated and aggregate together… which leads to the formation of a blood clot.

ADAMTS13 cleaves long VWF chains and helps to break down blood clots containing high levels of VWF and platelets.

ADAMTS13 may be useful as a new drug to break down blood clots after ischaemic stroke.

Investigator: Adam Greenstein

Blood vessels are the body’s irrigation system, enabling nutrients and oxygen in the blood to be delivered from the top of your head to the end of your toes. It is easy to think of blood vessels as pipes of a fixed size, which supply a set volume of blood to a particular organ.

However, this would lead to swelling of vulnerable organs such as the brain when blood pressure rises. Therefore, when blood pressure does increase, the arteries sense this, and become narrower to make sure blood flow is kept to a constant level and maintain optimum brain health.

In both Alzheimer’s disease and vascular dementia, there is a reduction in blood flow to the brain, which lowers the amount of nutrients and oxygen delivered to the brain. Over a period of time, this leads to loss of cognition.

Our research shows that in models of Alzheimer’s disease and hypertension-driven vascular dementia, the arteries are too sensitive to intraluminal pressure and over constrict to reduce cerebral blood flow.

Our research is identifying the mechanisms that drive this over-constriction and trying to pharmacologically restore the arterial function, helping identify novel treatments for people living with dementia.

Funder: Alzheimer’s Society
Local researchers: Laura Parkes, Ross Dunne, Karl Herholz, Oli Sparasci, Alistair Burns
External researchers: John O’Brien, Franklin Aigbirhio (University of Cambridge), Henrik Zetterberg (UCL)

Dementia is the leading cause of death in the UK, and Alzheimer’s underlies 60% of all dementia. There are currently no medications that slow progress available in the UK.

Disease-modifying medications for Alzheimer’s disease have been licensed in the United States and are under scrutiny by NICE. Evidence suggests that the protein abnormalities in Alzheimer’s disease (Beta amyloid and tau) can be detected in the CSF up to ten years before the onset of cognitive symptoms.

Our work is focused on getting research discoveries into clinical practice in the NHS. Our All-in-One Study, funded by the Alzheimer’s Society, will evaluate new brain scanning technologies alongside a blood test for Alzheimer’s disease, to see if we can speed up diagnosis and make It more accurate.

We are also working with our colleagues in The University of Manchester’s Hearing Health Biomedical Research Centre to evaluate the use of hearing tests to predict cognitive decline alongside novel blood biomarkers. While blood tests remain solely for research use, the analysis of cerebrospinal fluid – which bathes the brain – is being rolled out in our Mental Health Trust.

We are working with industry partners Stratastem and other companies to develop platforms for the development of new medications for use in Alzheimer’s and other diseases underlying dementia.

In conjunction with the UK’s Brain Health Collaboration, our novel clinic at brainHealth Manchester uses advanced cognitive testing, fluid biomarkers and neuroimaging to diagnose the earliest stages of Alzheimer’s and other neurodegenerative diseases, so that people can participate in research, and when the time comes, have disease-modifying medications to slow their progress.

• Learn more about the All-in-One study.

The Brain Inflammation Group focuses on stroke. It also investigates other cerebrovascular diseases such as Alzheimer’s disease and vascular dementia.

The team works to understand the inflammatory mechanisms in healthy versus diseased brains to identify novel therapeutic targets.

Twitter: @BIG_research