Developed by researchers from 91直播 University NHS Foundation Trust (MFT) and The University of Manchester, in collaboration with 91直播 based company genedrive, the test can tell healthcare professionals in approximately one hour if stroke patients will be more likely to benefit from clopidogrel, the current first-line treatment to prevent recurrence.

Approximately 100,000 people in the UK each year will have a stroke 鈥� a serious life-threatening condition that happens when the blood supply to part of the brain is cut off by a blood clot.

Clopidogrel prevents platelets (a type of blood cell) from sticking together and forming a dangerous blood clot. However, around 29 per cent of all patients in the UK (and up to 60 per cent in different ethnic groups) have a change in the CYP2C19 gene which reduces clopidogrel鈥檚 effectiveness.

Individuals carrying changes in the CYP2C19 gene are also twice as likely to have further strokes when treated with clopidogrel. If these genetic changes can be detected before treatment, then doctors can use an alternative, more effective medicine. 

Professor Bill Newman, Consultant in Genomic Medicine at MFT and Professor of Translational Genomic Medicine at The University of Manchester who led the project said: 鈥淪trokes affect more than 6,000 people in Greater 91直播 each year and those affected are at increased risk of further severe strokes in the following hours, days and weeks.

鈥淭his is clearly a particularly worrying time for patients and their families; therefore, it is vital we use new approaches to ensure that patients get onto the right treatment as quickly as possible.鈥�

Professor Newman, who is also Rare Conditions Co-Theme Lead at the National Institute for Health and Care Research (NIHR) 91直播 Biomedical Research Centre (BRC), added: 鈥淭his could reduce time spent in hospital, prevent further strokes, save lives, and avoid future hospital admissions.

鈥淚f adopted into routine practice, this rapid test, which has been recommended for use in the NHS by the National Institute for Health and Care Excellence (NICE), represents a major transformation in the way we manage stroke in this country.

鈥淥ur early model-based cost-effectiveness analysis published last year shows that using a rapid genetic test could lead to significant cost savings for the NHS. Using a rapid genetic test was 拢512 less expensive compared with no testing per patient, due to the prevention of secondary strokes and reduced hospital admissions. When you factor in the potential improvements in patient鈥檚 quality of life, the model estimates that the potential value of the test to the NHS is over 拢160 million each year.鈥�
 

Using a simple cheek swab, the non-invasive test can be performed at the bedside. From the swab, the genedrive system interprets the genetic information on the patient and informs the clinician with options on the course of treatment.

Previously, genetic testing for CYP2C19 could only be carried out using specialist laboratories, a process which can take several days.

The innovative test was used successfully at 91直播 Royal Infirmary and the 91直播 Centre for Genomic Medicine, Saint Mary鈥檚 Hospital, both part of MFT, over six months, to evaluate performance in the clinical setting.

Further testing will be carried out at Greater 91直播鈥檚 Hyper Acute Stroke Unit (HASU) at Salford Royal Hospital, part of Northern Care Alliance NHS Foundation Trust, to establish the benefit for patients across Greater 91直播. HASU is the largest dedicated unit in the region and provides care for people across Greater 91直播. This work is part supported by the Geoffrey Jefferson Brain Research Centre through the Edward and Victoria Bonham Carter fund and NHS England Network of Excellence in Pharmacogenetics and Medicines Optimisation.

This pilot is an important step in understanding the set-up costs, workforce and other requirements to roll out this innovation wider.

Dr John McDermott, Clinical Geneticist at MFT and NIHR Fellow from The University of Manchester said: 鈥淕enomic medicine is changing the future of healthcare and we are delighted NICE has recommended the use of the test in the NHS.

鈥淎s part of the NHS Genomic Networks of Excellence work that we are leading, we are now working with colleagues across the country to work out the best ways to introduce genetic testing for CYP2C19 for patients who have just experienced a mini-stroke (TIA) or acute stroke.鈥�

This research is part of the DEVOTE programme, an Innovate UK funded project coordinated by Health Innovation 91直播, led by The University of Manchester and supported by MFT.

The programme builds on research supported by the NIHR 91直播 BRC, hosted by MFT, which focuses on making pharmacogenetic testing more accessible to patients to improve clinical outcomes.

Dr Gino Miele, Chief Scientific Officer, genedrive plc, said: 鈥淭he collaboration of our company with the research and clinical team at MFT is a shining example of the NHS collaborating with a commercial company, from early product development through to clinical validation in real-world settings, to deliver real improvements in patient outcomes in a cost-effective way.  We are delighted with the positive recommendation from NICE and the success of the multi-disciplinary team collaboration under DEVOTE. We look forward to our CYP2C19 ID kit, the second point of care pharmacogenetic test developed in collaboration with this team for NHS use, being made available for the benefit of patients who have suffered a stroke or TIA.鈥�

Professor Ben Bridgewater, Chief Executive at Health Innovation 91直播, said: "The recommendation by NICE for the point-of-care test is a demonstration of how the DEVOTE programme is supporting the development, validation and implementation of innovative genomic tests in healthcare. The planned implementation testing at Northern Care Alliance NHS Foundation Trust is an important milestone for validating the use in a real-world setting of a personalised approach to provide healthcare to patients that have suffered a stroke. Providing better care for cardiovascular diseases is a high priority for Health Innovation 91直播 and we are committed to continue our support to the DEVOTE programme."

Juliet Bouverie OBE, Chief Executive of the Stroke Association said: "Stroke devastates lives and leaves people with life-long disability. We know that many stroke survivors spend the rest of their lives fearing another stroke, so it's great to see that more people could be given appropriate help to significantly cut their risk of recurrent stroke. Anything we can do to prevent the misery that stroke can cause is ultimately good news. Getting on the right medication and taking it as advised is the best way for stroke survivors to reduce their risk of further strokes.

"If you are a stroke survivor and have questions about the medication that you have been prescribed, you should keep taking your medication and contact your GP surgery.鈥�

The news offers hope that doctors may one day be able to investigate suspected kidney pathologies without carrying out invasive procedures such as biopsies, raising the tantalising prospect of earlier and simpler disease detection.

The impact of late detection of kidney disease can be severe and can lead to serious - and sometimes life threatening - complications.

The team led by University of Manchester scientists measured the levels of approximately 20,000 genes in each cellular sediment sample of urine using a technique called transcriptomics.

The British Heart Foundation-funded study benefited from access to the world's largest collection of human kidney samples collected after surgery or kidney biopsy conducted before transplantation, known as the Human Kidney Tissue Resource, at The University of Manchester.

They extracted both DNA and RNA from each sample and connected information from their analysis, together with data from previous large-scale analyses of blood pressure (called genome-wide association studies), using sophisticated computational methods.

Transcriptomics allows scientists to understand which genes are turned on or off in different situations so they can understand how cells respond to changes in their environment.

Such molecular-level understanding enhances the precision and effectiveness of diagnostic approaches, potentially improving patient care and outcomes.

The study, published in Nature Communications today (19/03/24) also showed that low levels of a specific gene in the kidney is likely to be one of the causes of high blood pressure.

The gene, called ENPEP, is an important part of the hormonal system which is essential for regulation of blood pressure, by making an enzyme called aminopeptidase A.

It was one of 399 genes identified by the researchers whose levels in the kidney are also causally related to either increasing or decreasing in blood pressure.

The study was led by Chair of Cardiovascular Medicine at The University of Manchester and Honorary Consultant Physician at 91直播 University NHS Foundation Trust.

He is also Integrative Cardiovascular Medicine Co-Theme Lead at the National Institute for Health and Care Research (NIHR) 91直播 Biomedical Research Centre (BRC), which supported the research.

He said: 鈥淭his study shows that using cutting-edge technology we are able to combine different unique datasets together using genetics as a connector.

鈥淥ne of the most exciting findings of that is we discover how cells harvested from urine have the potential to provide a glimpse into the molecular operation of the human kidney.

鈥淭hat gives us an exciting avenue of research for non-invasive diagnostic testing.鈥�

He added: 鈥淧ersistent high blood pressure鈥攐r hypertension鈥攃an increase the risk of a number of serious and potentially life-threatening health conditions, such as heart disease, heart attacks and strokes.

鈥淥ur results also show that the gene ENPEP in the kidney is a new promising target for development of new blood pressure lowering medications.

鈥淭here are several classes of effective antihypertensives available, though the last new medication approved for management of high blood pressure was over a decade and a half ago.

鈥淲hile for some people, they are effective, side effects make it difficult for others to take over the long term. That is why we need more choice.鈥�

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: 鈥淭here is a well-known link between the heart and the kidneys in regulating blood pressure. This study uses cutting-edge scientific techniques to analyse genes present in kidney cells that are normally expelled in the urine. Analysing these cells could reveal which genes may be playing a key role in people with high blood pressure, and could potentially offer clinicians a new, non-invasive way to help diagnose those with kidney disease early on.

鈥淗igh blood pressure is a major risk factor for heart disease and stroke, and this research has identified a gene called ENPEP that regulates important enzymes in the kidney that could be a promising target for blood pressure-lowering drugs. This study has demonstrated the power in using large sets of data and in doing so, shows how funding research like this can help us to improve treatment for people with high blood pressure.鈥�

The paper Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates  new blood pressure and hypertension targets  is available . The DOI for the paper is 10.1038/s41467-024-46132-y

Jessica Buckle is a Medical Biochemistry graduate who bravely battled to recovery from a stroke in the middle of her final year, which temporarily affected her mobility and sight.

Luckily, her sight came back after a week, but it still took eight weeks for her full mobility to recover, enabling her to walk independently once again. Reflecting on her journey, Jessica committed to completing her degree and graduating whilst on her recovery journey.

She said: 鈥淭he last semester of final year was completed from my family home in Euxton where I balanced recovery and my studies as best as I could, I contemplated deferring the year but I could see the finish line and I was so determined.

鈥淢y time at 91直播 has been a wonderful experience meeting so many friends that I will keep and have for the rest of my life.

鈥淚 would like to raise awareness of strokes in the younger generation as I had no idea younger people even had strokes at my age. I am so grateful for all my tutors and professors that helped me throughout this time at The University of Manchester and I am so thankful to be graduating with a 2:1 and lots of friends for life.鈥�

Strokes are a serious life-threatening medical emergencies resulting from interrupted blood supply to the brain. According the UK鈥檚 , strokes occur 100,000 times annually in the UK, once every five minutes 鈥� it also ranks as one of the leading causes of death and disability.

A conducted as part of World Stroke Day 2022 found a sharp increase in the incidence of stroke in young adults, in a study of more than 94,000 people in Oxfordshire.

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However, Dr Ivy Cheng, the University of Manchester research associate, who had reviewed evidence from over 30 randomised controlled trials, says there is unfortunately only limited evidence to support the efficacy of traditional swallowing therapy used by speech therapists for dysphagia.

One such neurostimulation approach is pharyngeal electrical stimulation (PES). This involves the insertion of electrodes through the nose or mouth which delivers a constant, low current to the pharynx- an important muscle in the execution of swallowing. The resultant stimulation has been shown to increase activity in the brain areas controlling swallowing.

By comparison, Repetitive Transcranial Magnetic Stimulation (rTMS) applies pulsing magnetic fields via a coil that is placed on the scalp to directly excite the underlying brain areas involved in swallowing.

A third treatment is Transcranial Direct Current Stimulation (tDCS) which uses a direct electric current to stimulate the brain directly, but this time using pads placed over the scalp in a certain orientation which, like a battery, has both anodal and cathodal configurations.

Her review found all three experimental treatments showed therapeutic potential for patients with dysphagia caused by stroke and other neurological causes and were tolerable without serious adverse effects.

However, the review - published in the Journal of the neurological sciences -  shows the variability in responsiveness to the treatment has hindered its translation into clinical practice and there is uncertainty as to how long these treatment effects might last in the medium to longer term.

鈥淒ysphagia is a condition which makes the everyday act of eating or drinking tortuous for patients,鈥� said Dr Cheng.

鈥淭his review shows neurostimulation has a great deal of potential, but we need long term studies to assess the best protocols for using neurostimulation in treating dysphagia.

鈥淲hich is why the news of a large clinical trial of pharyngeal electrical stimulation for post-stroke dysphagia, which is running from 2021 to 2025 involving 50 sites over 4 countries, including the UK, is so exciting.鈥�

Led by The University of , some of the work will be carried out by Dr Cheng鈥檚 colleague Professor Shaheen Hamdy from The University of Manchester.

Dysphagia occurs when some of the 50 muscles involved in swallowing do not work to close off the windpipe to protect the lungs so food and fluid trickle through vocal cords into the lungs.

Patients suffer from coughing and choking, as well as pain and voice problems when eating and drinking. Many avoid eating and others have recurrent chest infections.

Current treatment include using food thickeners, liquidising meals and referral to speech and language therapist (SLT) for swallowing therapy.

In the past, scientists thought that dysphagia was caused by problems in the brain stem alone, however more recent work has shown it is also linked to problems in the cerebral cortex.

When somebody suffers damage to the brain caused by stroke, Parkinson鈥檚, or other conditions, the part which controls swallowing might be damaged.

However the evidence reviewed by Dr Cheng showed that other parts of the brain can grow to compensate for the damaged areas鈥� a phenomena called neuroplasticity.

Thanks to neuroplasticity, neural pathways in the brain get stronger if they are used regularly. If a pathway is not used regularly, it disappears.

Neurostimulation, the studies showed, can help to promote this reorganization.

The paper Cerebral control of swallowing: An update on neurobehavioral evidence is available

Brain haemorrhages, or haemorrhagic strokes, occur when blood leaks from a blood vessel in or around the brain and in the UK accounts for about 15% of all strokes.

The reaction of the brain to the sudden presence of excess blood can lead to brain damage, disability and death 鈥� with almost a half of patients going on to die within a month as a result of suffering a brain haemorrhage.

Researchers at Nottingham Trent University are leading the work in collaboration with the University of Manchester, which aims to find a way to prevent the damage to brain cells caused by iron from the blood that builds up in the brain after a haemorrhage.

The researchers 鈥� funded by Brain Research UK 鈥� are focusing on drugs called 鈥榠ron chelators鈥�, which bind to iron to prevent its accumulation in the body.

They will package these iron chelator drugs into bubbles (鈥榣iposomes鈥�) which can be used to more effectively deliver drugs into the body.

It can be challenging to target drugs to affected areas of the brain due to the 鈥榖lood brain barrier鈥�, which works to prevent potentially harmful toxins in the body from reaching it.

But the team hopes its novel approach will enable the drug to stay in the blood stream for a longer period of time and allow enough drug to get to the area of the brain that contains the bleeding, while also not exposing the rest of the body to unnecessary side effects.

The work, which will involve the use of mice and patient samples, will take about three years.

The study involves a multidisciplinary team of scientists led by Nottingham Trent University鈥檚 Dr Zahraa Al-Ahmady in collaboration with Prof Stuart Allan, Dr Adrian-Parry Jones and Dr Ben Dickie at the University of Manchester and NTU鈥檚 Prof Sergio Rutella and Prof Graham Ball.

鈥淯nfortunately, no specific medications currently exist to prevent or treat brain haemorrhage,鈥� said lead researcher Dr Zahraa Al-Ahmady, a scientist in Nottingham Trent University鈥檚 School of Science and Technology.

She said: 鈥淭here are severe issues related to having this blood and iron accumulation in the brain, which contributes to the death of brain cells. We hope our approach will prevent this excess iron from damaging neurons and other tissue and be a new approach to blocking blood induced brain damage after bleeding.

鈥淢any of those who suffer a brain haemorrhage will sadly die and those who survive can have permanent disabilities and so the creation of new drugs is essential. We are aiming to find a way to enable treatment to better infiltrate the brain and to remain at the disease site for longer before more serious damage occurs.鈥�

Professor Stuart Allan of the University of Manchester said: 鈥淚t is exciting to be working in partnership with researchers at Nottingham Trent University on this project. The death rates due to brain haemorrhage have not changed for several decades. This sort of research is therefore vital to find the new treatments necessary to improve survival.鈥�

Caroline Blakely, Chief Executive of Brain Research UK, said: We鈥檙e excited to be funding this important work by Dr Al-Ahmady and collaborators, and hope that it will prove to be an important step towards improving outcomes for patients who have suffered a brain haemorrhage.

鈥淲e are only able to fund research like this thanks to the extraordinary efforts of our supporters, many of whom are raising funds in tribute to loved ones affected by brain conditions.鈥�

The compound – an enzyme called caADAMTS13 –could dissolve clots in patients that are resistant to current treatment, according to the study published in the journal Blood today (15/11/21).

The study of the novel compound - which is patented by the team- was funded by the British Heart Foundation.

tPA - currently used by doctors in the acute phase of a stroke - works for many patients, however, it is not able to break down clots which are rich in Von Willebrand Factor (VWF), a large string shaped protein molecule which plays a crucial role in clot formation.

Around 50% of all clots are rich in VWF - which tethers circulating clotting cells called platelets at sites of clot formation - and that are resistant to tPA.

The team examined the efficacy of the drug in mice and compared it with the wildtype variant of the enzyme - called wtADAMTS13 that occurs naturally in the body.

When given 1 hour after a stroke, the new drug significantly reduced VWF by dismantling its long chains - five times more quickly than the wildtype variant achieved.

The drug also prevented a type of white blood cell called a neutrophil from entering the brain tissue starved of blood supply and thought to be a cause of the damage to brain cells.

VWF is also implicated in the recruitment of neutrophils to the site of clot formation, which impacts on the stability of the clot and it’s likelihood of breaking down into smaller fragments.

Stroke is caused by a reduction in blood flow to the brain – which most frequently results in loss of movement, problems with speech and other symptoms in the patient.

The reduced blood flow is most often caused by a blood clot that lodges in the narrow blood vessels that supply the brain, which means the cells of the brain don’t get the energy they need to work.

If blood flow is not quickly restored the brain cells will die leading to permanent brain damage and, if severe, death.

Current treatments for stroke are focussed on removing the blood clot to restore blood flow to the brain. In many patients this treatment works well, and the patients recovers function.

However, in many patients the blood clot is not broken down by the drug treatment and symptoms persist.

With tPA, there is an increased risk of haemorrhage occurring if it is given from about 4.5 hours after the stroke occurred.

Co Author Professor Stuart Allan from The University of Manchester and Co-Director of the Geoffrey Jefferson Brain Research Centre said: “Our novel drug is able break down the blood clots that are resistant to the current treatment tPA. In doing so, more stroke patients could show recovery of function than at present.

“Clearly there is still some way to go, and we need to know if the drug is effective a period of time after the stroke has occurred – with less risk of haemorrhage .

”We are optimistic that we will be able to show this drug can to do that; once we have, we hope to move onto human trials. It’s very exciting.”

Co-author Dr Kieron South, from The University of Manchester has worked for some time on developing the ADAMTS13 variant.

He said: “The therapeutic landscape for the treatment of stroke has looked bleak for some time.

“Despite promising pre-clinical and early clinical trials, few candidate therapies fulfilled their early promise and none have so far been able to replace tPA as the first line anti-thrombolytic therapy.

“However, several pre-clinical studies identified a potential alternative thrombolytic therapy to tPA in the form of recombinant human (rh)ADAMTS13.

“That too was impractical- as it needed to be given in very large doses and early on after the stroke is occurring for it to work.

“But it is possible to manipulate its structure into a much more active form of the enzyme , the caADAMTS13 used in this study, by identifying a part of the molecule that is needed to disassemble Von Willebrand Factor.

Co-author Craig Smith, Professor of Stroke Medicine at The University of Manchester and Consultant in stroke medicine at 91直播 Centre for Clinical Neurosciences, Northern Care Alliance NHS Group said: “A stroke strikes every five minutes in the UK and can happen at any time at any age.

“Its effects can be life changing but as of yet, clot-busting treatment needs to be more effective and safer for patients.

“The caADAMTS13 variant has exciting potential and could - if proven effective- lead to many more patients recovering after a stroke caused by a blocked artery.

“But not only does it represent a potentially viable therapeutic option for the treatment of stroke, it could also have potential in other conditions where blood clots are implicated, including heart attack and pulmonary embolism.

 Robust Thrombolytic and Anti-Inflammatory Action of a Constitutively Active ADAMTS13 Variant in Murine Stroke Models is published in Blood

Gifts to the appeal – launched in December 2020 – will fund a new PhD research post with a focus on haemorrhagic stroke. The new researcher will increase capacity in the 91直播 stroke team and support the search for life-saving new treatment.

Haemorrhagic stroke – otherwise known as brain haemorrhage – is a subtype of stroke. Around half of all patients who experience this type of stroke will die, and this death rate has changed very little in the past thirty years. This is in stark contrast to other diseases that have seen death rates reduce substantially over that time.

There is currently no successful treatment for haemorrhagic stroke – making this is a key area of research focus for the 91直播 Stroke Group. The University’s strengths in Neuroscience research and links with the UK’s largest clinical stroke centre make 91直播 particularly well-placed to lead the search for better treatments.

Professor Stuart Allan leads the team that will welcome the new PhD researcher, and expressed his gratitude to the hundreds of donors who have helped to fund the new post:

“Thanks to hundreds of donors, we’ll be able to strengthen our team with crucial expertise which will drive our research on to new levels. With an extra researcher on the team, I’m confident we’ll make quicker progress towards a much-needed treatment for haemorrhagic stroke. In a few short months, our University community has come together, and made our dream of expanding 91直播’s stroke team a reality.”

The appeal has also been championed by Fiona Moss of the . Fiona tragically lost her sister Natalie to a haemorrhagic stroke nine years ago, and the Trust have been generous supporters of the University’s stroke research ever since. Fiona said:

“Thank you so much to everyone who has donated over the last few months to such an incredibly worthwhile appeal. My family and I know first-hand the struggles and heartbreak that stroke can cause. That’s why we’re so proud to support Professor Allan and his excellent team, and why we’re so excited to hear about the progress that the 91直播 stroke team will make, thanks to your help.”

With funds now in place, Professor Allan and team will start making plans to recruit the new researcher. The appeal remains open, and any further donations will be used to fund resources and equipment to support the new researcher’s work.

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Swarms of nanoparticles which are 15,000 times smaller than a pinhead may be able to deliver vital drugs to the brain, offering new hope to patients in the early stages of a stroke.

The research, carried out at The University of Manchester, shows that tiny vesicles called liposomes, just 100 nanometres in diameter can translocate through the damaged blood brain barrier following stroke.

And that may offer a way to get vital drugs to the lesions to stop further damage.

The brain is the only organ to have its own security system: a tightly packed network of blood vessels and barriers that allow the entry of essential nutrients while blocking other potentially harmful substances.

However, the barrier also blocks lifesaving drugs, rendering it difficult to treat a range of conditions including stroke.

Now the research carried out on mice and published today in the journal , shows that liposomes can potentially transport life-saving drugs across the barrier.

The researchers were able to generate microscopic pictures of the brain tissue using state of the art imaging techniques, showing the nanomaterial is a viable transporter.

Up to now, scientists haven’t yet devised a reliable way to deliver drugs to damaged brain efficiently – one of the last frontiers in medical science.

But now the team show that following a stroke event, liposomes are able to penetrate the brain by being transported across the tightly packed endothelial cells by using pouch-like structures known as caveolae.

That means doctors might one day be able to protect tissue in the acute phases of a stroke, by delivering drugs - still being developed - that can protect brain’s neurons from further injury.

In the days following a stroke, when brain cells - or neurons- have died, the researchers showed that liposomes are also able to penetrate the brain to help promote the repair of neurons.

Liposomes are made from lipids which are long chains of oily or waxy organic molecules found in all living things.

Stuart Allan Professor of Neuroscience from The University of Manchester said: “The discovery that nanomaterials may be able to facilitate the treatment of stroke is exciting: scientists have long been grappling with the difficulties of treating brain injuries and diseases.”

“The brain blood barrier is a major frontier in neurology, so the prospect of being able to cross it may have applications to other conditions as well – though clearly, much more work needs to be done.”

Dr Zahraa Al-Ahmady, Honorary Research Fellow at The University of Manchester and a Senior Lecturer at Nottingham Trent University, said: “Liposomes are a tried and tested method of delivering drugs to the body – and are currently used to treat patients, for example, to target cancer drugs into the tumour at high doses which increase their concentration relative to other parts of the body. “

“They are easy to manufacture and used across the NHS. But our research shows that Liposomes have important implications for neurologists too.”

Professor Kostas Kostarelos, Chair of Nanomedicine at The University of Manchester said: “This discovery is an important milestone on the use of liposomes for yet another debilitating disease, such as stroke. Liposomes have had a tremendous impact on offering treatment options in oncology, vaccination, lung and skin disease since they were first discovered by British haematologist , FRS in 1965.”

The paper ‘Selective Liposomal Transport Through Blood Brain Barrier Disruption in Ischaemic Stroke Reveals Two Distinct Therapeutic Opportunities’ is available here

A new treatment has been shown to significantly improve the speech and word production of stroke patients.

The treatment- developed by a speech therapist and cognitive neuroscientists at The University of Manchester- uses special software which gradually makes patients produce words increasingly quickly.

The researchers – who publish their findings in the journal Brain today – hope that the treatment will eventually improve the ability of stroke patients with aphasia across the NHS to access intensive treatment, and improve their symptoms and speech recovery after stroke.

The new treatment- tested on 20 stroke patients – was shown by the researchers to be around twice as effective in terms of words deployed by the patients in their speech.

The treatment, which is administered over several training sessions, uses photos shown on a laptop, initially giving patients 3 seconds to react. Gradually, the time is reduced, aiming to achieve a response of 1 second – which is normal for people over 65.

The research was funded by , and .

The researchers are based at the University of Manchester’s .

, Clinical Lecturer in Speech and Language Therapy, said “We know from Stroke Association data that there are more than 100,000 strokes in the UK each year, that is around one stroke every five minutes.

“So there are over 1.2 million stroke survivors in the UK and about one third of stroke survivors will have aphasia as a long term disability.”

Dr Conroy explained: “And though symptoms can vary, the consequences of aphasia at its worst can be devastating; not being able to use words, understand, read or write words can be very tough even at the less affected end of the spectrum.

“So we’re excited this new approach seems to yield significant benefits.”

The researchers tested three measures, each compared to standard speech therapy treatment – and then retested the patients after a month.

The accuracy of the patients’ word retrieval was 25% better with the treatment and 10% better with the standard treatment.

Deployment - the use of words appropriately in speech – rose from 17% to 59% after treatment, compared to 14% to 33% with standard treatment. Patients with no treatment at all improved from 15% to 24% - so the impact of standard treatment was limited.

And in terms of speed of response, patients improved from 3 seconds to 1.6 seconds with the new treatment and 3 seconds to 2 seconds with standard treatment. However, the effect of the standard treatment was lost after a month whereas the effect of the new treatment remained.

who is a cognitive neuroscientist said: “This is a novel approach: we had not really considered before that speed of naming seems to play an important part in speech therapy.

“It’s cheap, quick to administer and more effective than current treatments.

“However, now that we have proof of principle, we hope to move on to a larger scale multi-centre trial.

“But our ultimate aim is for this treatment to be available for the NHS within 5 years.”

The paper ‘’ is published in Brain DOI: 10.1093/brain/awy087

An anti-inflammatory drug given to patients in the early stages of a stroke has been shown by researchers at The University of Manchester and Salford Royal NHS Foundation Trust to reduce harmful inflammation.

The drug, Kineret©, licenced for treating rheumatoid arthritis, was given as a small injection just under the skin without giving the patients any identifiable adverse reactions.

It is one of many biologic agents transforming treatment in a range of illnesses.

The protein Interleukin-1 (IL-1) is part of the body’s defences and naturally produced to combat a range of illnesses.

However, scientists at The University of Manchester have previously shown IL-1 increases inflammation and brain injury following a stroke.

Kineret works by blocking the actions of IL-1 which is released into the body following injury caused by a stroke.

The researchers, who have published their findings in the journal Stroke, cannot say for sure at this stage how the reduction in inflammation will impact on clinical outcomes.

The study, funded by the Stroke Association, follows earlier research that shows the drug given as an intravenous therapy reduces inflammation in stroke and sub arachnoid haemorrhage patients.

A stroke occurs when poor blood flow to the brain results in cell death. There are two main types of stroke: ischemic, caused by lack of blood flow, and haemorrhagic, caused by bleeding in the brain.

Stroke is the most common cause of disability in adults and a leading cause of death worldwide.

The 91直播 study - a double blind trial where Kineret was tested against placebo - looked at ischemic strokes only.

The 80 Participants in the study -carried out at Salford’s Greater 91直播 Stroke Centre at Salford Royal– were given 6 doses of the drug or placebo over three days. The first dose was given within 6 hours after the onset of the stroke symptoms.

Inflammatory markers were measured in the blood before treatment began and during study treatment.

Professor Craig Smith from The University of Manchester is also a stroke physician at Salford Royal.

He said: “Though Strokes affect different people in different ways, for many people they have a devastating effect on their long-term health and wellbeing.

“Excessive inflammation after a stroke is known to be harmful and predicts a worse outcome in patients.”

“We have shown that Kineret injections, started within six hours of stroke onset significantly reduces levels of inflammation in patients.”

Hilary Reynolds, Executive Director of Strategy & Research at the Stroke Association said: “This study builds on evidence that IL-1Ra (Kineret) helps to reduce inflammation and brain damage in a wide range of stroke patients soon after a stroke. The drug can be given quickly, via injection or via a drip. This means that it can be used in different settings, for example, it could potentially be given in ambulances on the way to hospital. The brain loses around 2 million brain cells every minute during a stroke, so this could provide a major step forward in fast and effective treatment of stroke.

“The research has not yet proven that this drug can reduce patient disability after stroke. However, if further trials are successful, we hope it could vastly improve outcomes and quality of life for people who have had a stroke.”

Further research is needed to see whether Kineret is an effective treatment for ischemic stroke and whether it can be given alongside current treatments such as clot-busting drugs (thrombolysis).

The same research team have shown that Kineret reduces inflammation and is safe in patients with bleeding around the brain, a condition known as subarachnoid haemorrhage.

To definitively test if Kineret improves patient outcomes in subarachnoid haemorrhage, a national trial of Kineret in 1000 patients, funded by the Medical Research Council and National Institute for Health Research, will start in 2018.

And another trial in 80 patients with stroke caused bleeding in the brain, known as intracerebral haemorrhage, will also start in 2018. It is funded by the National Institute for Health Research.

That trial will test if markers of inflammation are reduced by Kineret and test safety in intracerebral haemorrhage.

The paper, subcutaneous interleukin-1 receptor antagonist in ischemic stroke : a randomized controlled phase 2 trial is published in

Intensive speech and language therapy can significantly help stroke patients who have been struggling to communicate for six months or more, according to newly published research.

Dr Stefanie Abel from The University of Manchester, co-author of new study, says patients with chronic aphasia need far more than they are currently getting on the health services to help them improve their everyday communication and health-related quality of life.

The multicentre RCT study – carried out in Germany and published in The Lancet - has for the first time directly demonstrated the superiority of intensive speech therapy to no treatment or treatment at low intensity in chronic post-stroke aphasia.

The project team was led by Dr Caterina Breitenstein, University of Muenster, and Prof Annette Baumgaertner, University of Applied Sciences Fresenius in Hamburg.

Currently, German patients with chronic aphasia - the inability to comprehend and formulate language because of damage to the brain’s language network – usually get around 1.5 hours of speech therapy a week, as reflected in the control condition of the present project. This intensity of treatment turned out to be ineffective.

Dr Abel argues intensity should be drastically increased for treatment to be effective.

The 156 patients in the study with chronic aphasia were given speech therapy that was individually targeted at each patient’s performance profile.

For example, if speaking in full sentences and word finding was impaired, therapy focused on these tasks, together with training of everyday messages.

The regime was delivered under regular clinical conditions with an intensity of at least 10 hours/week for 3 weeks, resulting in a 10% improvement on average. For patients who received therapy for at least five and up to 10 weeks, effectiveness was even higher.

The team identified significant improvements in verbal communication, linguistic abilities, and quality of life ratings in the immediate and longer-term.

However, non-verbal learning skills and executive functioning were not affected by the regime, underlining, says Dr Abel, the need for treatment to be specifically tailored to the respective deficits to be effective.

Future studies may investigate which level of intensity is required for a similar effect, to allow speech therapy to be both effective and efficient.

Dr Abel was speech therapy supervisor in the project and developed the impairment-based outcome measure, from which all linguistic exercises in the study were derived. She said: “It’s one thing to anticipate that higher intensities of speech therapy will improve the verbal communications skills of stroke patients, but it’s another to prove it.

“We can now be certain that this more intensive regime will work for the majority of these patients, and could provide important opportunities for them to cope better with this debilitating problem.

“We expect and hope our trial to have great impact on clinical practice and health care for people with aphasia internationally.

“Now the evidence is out there, we hope health services will take note.”

The project was funded by the German Ministry for Education and Research (BMBF) and the German Society for Aphasia Research and Treatment (GAB).

The paper “Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting” can be downloaded at (2016, free accepted version). The final version is available from Dr. Abel (stefanie.abel@manchester.ac.uk) or can be downloaded at:

Researchers at The University of Manchester have discovered that a potential new drug reduces the number of brain cells destroyed by stroke and then helps to repair the damage.

A reduction in blood flow to the brain caused by stroke is a major cause of death and disability, and there are few effective treatments.

A team of scientists at The University of Manchester has now found that a potential new stroke drug not only works in rodents by limiting the death of existing brain cells but also by promoting the birth of new neurones (so-called neurogenesis).

This finding provides further support for the development of this anti-inflammatory drug, interleukin-1 receptor antagonist (IL-1Ra in short), as a new treatment for stroke. The drug is already licensed for use in humans for some conditions, including rheumatoid arthritis. Several early stage clinical trials in stroke with IL-1Ra have already been completed in 91直播, though it is not yet licensed for this condition.

In the research, published in the biomedical journal Brain, Behavior and Immunity, the researchers show that in rodents with a stroke there is not only reduced brain damage early on after the stroke, but several days later increased numbers of new neurones, when treated with the anti-inflammatory drug IL-1Ra.

Previous attempts to find a drug to prevent brain damage after stroke have proved unsuccessful and this new research offers the possibility of a new treatment.

Importantly, the use of IL-1Ra might be better than other failed drugs in stroke as it not only limits the initial damage to brain cells, but also helps the brain repair itself long-term through the generation of new brain cells.

These new cells are thought to help restore function to areas of the brain damaged by the stroke. Earlier work by the same group showed that treatment with IL-1Ra does indeed help rodents regain motor skills that were initially lost after a stroke. Early stage clinical trials in stroke patients also suggest that IL-1Ra could be beneficial.

The current research is led by , who commented: “The results lend further strong support to the use of IL-1Ra in the treatment of stroke, however further large trials are necessary.”

The paper, ‘Reparative effects of interleukin-1 receptor antagonist in young and aged/co-morbid rodents after cerebral ischemia’, was published in the journal Brain, Behavior and Immunity. DOI: 10.1016/j.bbi.2016.11.013

Paper available under open access .

Funding for the research was provided by .

Researchers at The University of Manchester are to investigate 160,000 patient records to identify issues affecting the quality of stroke therapy in England.

Around 1.2million people in the UK are classed as stroke survivors with around 150,000 new incidences of stroke each year. Although three quarters of people survive their stroke, many are left with problems which impact on their quality of life.

Therapy is one of the most important ways of helping these people regain their quality of life but in England most people do not seem to achieve the recommended 45 minutes a day of therapy.

The University of Manchester research team working with colleagues from King’s College London, funded by the HS&DR Programme, will use the records from the Sentinel Stroke National Audit Programme (), a database of which tracks patients’ progress from the first ambulance call to six months after their discharge from hospital. The research team will use the most recent available 160,000 records stemming back to 2013.

Professor of Rehabilitation, , is leading the research. She said: “SSNAP is the first database of its kind anywhere in the world and access to it means we can find underlying reasons for any variations in the quality of stroke care and propose cost-effective ways of doing something about it.”

Therapy covers a diverse range of activities designed to help people regain their independence after a stroke. Issues that therapy tackles include speech and mobility problems and regaining ‘thinking skills’ which let patients return to work, or resume their previous lives as much as possible. Early intervention is important to the success of this therapy as is ongoing support for the patient once they have been discharged back into the community.

In the study which is funded with £221,446, various factors such as the type and amount of therapy received, how services are organised and what the outcomes for patients are, will all be analysed and at the end of the two-year study a series of detailed recommendations will be issued.

Professor Tyson added: “The raw data from SSNAP gives a value description of how stroke services are delivered but it does not explain how factors are inter-linked; why therapy does (or does not) happen; how much therapy services cost, nor which are the most effective ways of organising therapy services in terms of maximising therapy, recovery or value for money. We will work this out.

“This important information is needed to make sensible, evidence-based decisions about how to improve therapy services so that as many stroke survivors as possible, get as much therapy as possible and make as much recovery as possible.”