Researchers aim for rapid biomarker diagnostic test for stroke, using saliva

The study aims to identify biomarkers in blood, urine, or saliva, for rapid diagnosis so patients are routed directly to the most appropriate treatment centre.

20 July 2023

Paramedics inside an ambulance securing a patient on a gurney — Full assessment usually takes place at a Hyperacute Stroke Unit and is followed by transfer to a specialist neuroscience unit for treatment. In the UK, this transfer can add at least an hour to the treatment pathway.

Birmingham researchers are set to collaborate on a study that could result in a rapid non-invasive diagnostic test to quickly and accurately identify stroke patients who need time-critical treatment before irreversible brain damage occurs.

Funded by the Stroke Association, the Golden HOur for STroke (GHoST) study will involve the West Midlands Ambulance Service University NHS Foundation Trust, Midlands Air Ambulance Charity, and University Hospitals Birmingham NHS Trust and industry partner Marker Diagnostics. A successful outcome could also revolutionise the way emergency treatment for stroke is managed.

Rapid transfer to hospital and diagnosis is incredibly important if stroke is suspected. Time lost is brain lost, which is why rapid diagnosis and treatment are key to reducing risk of death and severity of disability. Some treatments, such as thrombolysis (clot busting drugs) or mechanical thrombectomy (manual clot removal) are most effective when administered within hours of symptom onset.

Ambulance personnel currently use symptom checklists to identify stroke, with a full assessment usually taking place at a Hyperacute Stroke Unit and followed by transfer to a specialist neuroscience unit for treatment. In the UK, this transfer can add at least an hour to the treatment pathway.

The GHoST study, led by Professor Antonio Belli, Professor of Trauma Neurosurgery at the University of Birmingham’s Institute of Inflammation & Ageing, aims to identify biomarkers (small molecules) in blood, urine, or saliva, that will enable rapid diagnosis so patients can be routed directly to the most appropriate treatment centre.

We are excited to be funding this study because it has the potential to reduce death and disability caused by strokes, both in the UK and around the world.
Dr Richard Francis, Head of Research at the Stroke Association

Professor Belli’s research team has previously identified that the concentration of specific molecules in saliva changes rapidly after a traumatic brain injury. A three-year study in elite rugby established that these biomarkers can be used in next-generation diagnostic tests that can rapidly and reliably detect concussion.

He explained: “Our previous studies detected ultra-early biomarkers and cellular responses that had never been reported in human studies before and resulted in a non-invasive diagnostic test that could change the way concussion is managed. In conjunction with our industry partner Marker Diagnostics, we’re now looking to repeat this success with stroke.”

The GHoST study will use the same methodology as these previous highly successful trials. Trained paramedics will collect saliva, blood and urine samples from patients with suspected stroke within the first hour after the onset of symptoms. Further sampling of blood, saliva and urine will continue in hospital, while patients receive standard clinical care.

The research team will pay particular attention to salivary small non-coding RNAs (sncRNAs). These small molecules, which are abundant in saliva, were probably the most exciting discovery in previous studies, which showed that they could be used in tests to differentiate between concussed and non-concussed patients.

The funding from the Stroke Association will include support from biotech company Marker Diagnostics UK to bring their Birmingham Biohub lab’s sncRNA discovery and commercialisation expertise into the study. Marker has already developed a CE-certified concussion test for adult males following the ground-breaking research from the University of Birmingham, and Marker’s research scientists will use a proprietary sncRNA collection, analysis technology and IP to develop a commercial and adoption pathway for any tests that may arise from this research.

While the GHoST study will be the first to investigate whether there are sncRNAs that are specific to stroke, previous studies have confirmed stroke-specific RNA biomarkers in the blood.

The researchers hope to identify sncRNAs that will accurately identify stroke and distinguish it from stroke-mimicking conditions, such as seizure or migraine, which account for 30-40% of emergency ambulance admissions with suspected stroke.

They will also be investigating whether biomarkers can differentiate between the two main types of stroke (ischaemic and haemorrhagic) which need diametrically different treatment. Ischaemic stroke, caused by a blood clot, accounts for over 80% of strokes and requires either clot-busting drugs or the surgical removal of the blood clot via an artery (thrombectomy), while haemorrhagic strokes, caused by a brain bleed, may require brain surgery.

Our previous studies detected ultra-early biomarkers and cellular responses that had never been reported in human studies before and resulted in a non-invasive diagnostic test that could change the way concussion is managed. In conjunction with our industry partner Marker Diagnostics, we’re now looking to repeat this success with stroke.
Professor Antonio Belli, Institute of Inflammation & Ageing, University of Birmingham

Dr Richard Francis, Head of Research at the Stroke Association said: “We are excited to be funding this study because it has the potential to reduce death and disability caused by strokes, both in the UK and around the world. Currently, paramedics in the UK rely on the FAST test to assess whether someone is having a stroke. In the absence of brain scanning equipment, FAST is the best diagnostic tool we have. This diagnostic test offers the potential to diagnose stroke in patients more quickly, enabling suitable patients to receive appropriate treatment speedily, therefore, leading to better outcomes.”

It’s essential to contact emergency services immediately if a stroke is suspected. The world-famous stroke acronym, FAST helps people to recognise the signs and symptoms of a stroke: Face, Arms, Speech, and Time (to call an ambulance) – Act FAST.

Dr Francis added: ”FAST is not perfect. At the moment, paramedics can mis-diagnose other conditions, such as seizures, as stroke, and not all stroke patients have FAST symptoms. Having a saliva test would be a massive step forward in pre-hospital diagnosis for stroke and really help people to get the right diagnosis, to get to the right hospital for the right treatment and in the quickest time. The potential success of this trial may also massively benefit countries without ready access to brain scanning equipment.”

The study will run for three years, with results expected in late 2026

Notes for editors

For media information contact Ruth Ashton, University of Birmingham Enterprise, email: r.c.ashton@bham.ac.uk

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About the Stroke Association

Stroke strikes every five minutes in the UK, and it changes lives in an instant.

The Stroke Association is a charity working across the UK to support people to rebuild their lives after stroke. We believe that everyone deserves to live the best life they can after suffering a stroke. From local support services and groups to online information and support, anyone affected by stroke can visit the website or call the dedicated Stroke Helpline on 0303 3033 100 to find out about support available locally.

Our specialist support, research and campaigning are only possible with the courage and determination of the stroke community and the generosity of our supporters. With more donations and support, we can help rebuild even more lives.

You can follow us on Twitter, Facebook, and Instagram.

About Marker

Marker Diagnostics is a subsidiary of Swiss medical device developer Marker AG and specialises in developing diagnostic and prognostic devices using non-coding RNA. Marker’s patented and CE marked MDx.100 Concussion/mTBI Diagnostic, a salivary diagnostic test, approved for mild traumatic brain injury in adult male athletes, is the only biological concussion diagnostic for concussion, a brain injury that has historically been challenging to diagnose.

Through the analysis of small non-coding RNA biomarkers in saliva, the test is an important component in identifying concussions and managing safe return to play in sport and the community. The company is also an active collaborator and lead developer of diagnostic and prognostic tools for other currently unmet medical needs.

About the West Midlands Ambulance Service NHS Trust

West Midlands Ambulance Service University NHS Foundation Trust serves a population of 5.6 million people covering an area of more than 5,000 square miles made up of Shropshire, Herefordshire, Worcestershire, Staffordshire, Warwickshire, Coventry, Birmingham and Black Country conurbation. As the region’s emergency ambulance service, WMAS respond to around 4,000 ‘999’ calls each day. To manage that level of demand, they employ approximately 7,000 staff and operate from 15 new fleet preparation hubs across the region.

West Midlands Ambulance Service University NHS Foundation Trust is delighted to be rated as ‘outstanding’ by the health and social care regulator, the Care Quality Commission (CQC); the highest possible rating. The Trust’s previous inspection also received a rating of ‘outstanding’ and has maintained its position as the only ambulance service to be rated as such.

About the Midlands Air Ambulance Charity

Who are we?

Midlands Air Ambulance serves the largest air ambulance region in the UK. This includes the communities of Gloucestershire, Herefordshire, Shropshire, Staffordshire, West Midlands, and Worcestershire, representing a population in excess of six million.

What do we do?

The charity responds to an average of 4,500 missions each year. We’re a helicopter-led service with over 2,000 deployments being air missions. We also have a fleet of Rapid Response Vehicles and three critical care cars. On average Midlands Air Ambulance Charity is one of the longest-established and busiest air ambulance operators in the UK.

Our lifesaving service

The three air ambulance helicopters are based at RAF Cosford airbase, near Shifnal, Shropshire, Tatenhill airbase, near Burton-on-Trent Staffordshire, and Strensham Services on the M5 located on the Gloucestershire / Worcestershire border. The charity’s three aircraft each carry a crew comprising a pilot, two paramedics or flight doctors plus full life-support medical equipment. The three critical care cars are based in the West Midlands (central car – serving the Birmingham and Black Country areas), the charity’s Strensham airbase (southern car), serving Gloucestershire, Herefordshire and Worcestershire and the charity’s northern car, which covers Shropshire, Staffordshire and Stoke-on-Trent. The charity’s cars each have critical care paramedics on board with full life-support medical equipment.

Time is critical

The sooner a patient receives enhanced pre-hospital emergency care on-scene, the greater their chances of survival and the better their outcome. We aim to bring that level of care to them, wherever they are, as soon as possible. In 2020/21 the average time to a patient was just ten minutes.

The cost

Each year it costs between £11-£12 million just to keep the three charity helicopters and three critical care cars operational. Each air ambulance mission costs £2,950 on average and each critical care car mission costs £288, which is entirely funded by the generosity of the public and local businesses.

Midlands Air Ambulance Charity press contact: 0800 840 20 40 / press@midlandsairambulance.com

About University Hospitals Birmingham NHS Trust

University Hospitals Birmingham NHS Foundation Trust (UHB) runs Heartlands, Good Hope, Solihull and the Queen Elizabeth hospitals; UHB also hosts the Institute of Translational Medicine (ITM).

The Trust has over 2,600 beds, 80 theatres and a 100-bedded critical care unit - the largest in Europe and cares for over 2.2 million patients each year, employing over 24,000 staff.

The NHS Long Term Plan (LTP) highlighted the need for Integrated Stroke Delivery Networks (ISDNs) to bring people and organisations together to deliver the best possible care for their population. The West Midlands ISDN was setup in 2021 and is hosted by University Hospitals Birmingham NHS Foundation Trust. It includes providers and service commissioners from across the whole stroke pathway.

The West Midlands ISDN is responsible for designing and delivering optimal stroke pathways. This will ensure that more people who experience a stroke receive high-quality specialist care, from pre-hospital, through to rehabilitation and life after a stroke. Pathway development is key to delivering the LTP stroke commitments.

UHB has a particular focus on research into treatments in the first 24 hours after a stroke and is designated as a Hyper-acute Stroke Research Centre (HSRC).

Our hospitals are regional centres of excellence for trauma, burns, plastics, neurosciences and cancer, and in 2014 became a lead genomics centre as part of the NHS 100,000 genomes project.

Featured staff

Professor Antonio Belli
Professor of Trauma Neurosurgery
Staff profile for Professor Tony Belli, Professor of Trauma Neurosurgery, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, the Unviersity of Birmingham
Phone: +44 (0) 121 414 4497
Email: a.belli@bham.ac.uk