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Birmingham researchers join Nobel Prize winner to win major funding on chronic inflammation

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

Researchers at the University of Birmingham will lead a major research programme to transform the treatment of autoimmune diseases by halting chronic inflammation at its source, working in partnership with 025 Nobel Prize winner Professor Shimon Sakaguchi, from Osaka University, and Professor Calliope Dendrou from the University of Oxford.

Backed by a £3.83 million Wellcome Discovery Award, the ambitious eight-year programme brings together world-leading scientists and clinician-scientists to focus on understanding and controlling the immune system’s regulatory mechanisms, with a particular focus on the liver.

Research will focus on the role of Foxp3+ Regulatory T-cells in maintaining immune tolerance and preventing tissue damage caused by autoimmune responses. Scientists and clinicians in the UK and Japan will explore how these Regulatory T-cells discovered by Professor Sakaguchi can be used to restore immune balance and treat autoimmune diseases.

Project leader Ye Htun Oo, Professor of Autoimmune Liver Diseases, from BHP founder-member the University of Birmingham, has been working in research partnership for more than 12 years with Professor Sakaguchi who was announced this week as one of three co-winners of the 2025 Nobel Prize in Physiology or Medicine – alongside US scientists Mary Brunkow and Fred Ramsdell – for their work understanding how Regulatory T-cells maintain a healthy balance within the immune system, creating openings for possible new autoimmune disease and cancer treatments.

Professor Oo commented: “Congratulations to Professor Sakaguchi on his Nobel Prize success – we are looking forward to continuing the University of Birmingham’s longstanding research partnership with him as we explore together how the Regulatory T cells that he discovered 30 years ago can help to treat autoimmune liver diseases.”

He also commented that Birmingham is one of the biggest liver transplant centres in Europe and this new approach of controlling autoimmune diseases with Regulatory T cells, will give hope to prevent liver transplantations for autoimmune liver diseases in future.

Autoimmune diseases occur when the body’s immune system mistakenly attacks its own tissues. In liver diseases such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, there is currently no cure, leading to chronic inflammation, organ damage, and loss of function and eventually requiring liver transplantations.

Professor Sakaguchi commented: “This exciting collaborative award will allow us to work together to understand stable functional regulatory T cells biology and to progress towards future therapy with these cells for patients with autoimmune liver diseases and multi-organ autoimmunity.”

The programme unites the expertise of Professors Sakaguchi and Professor Oo with Professor Graham Anderson, from the University of Birmingham – a leading authority on thymic T-cell development and immune tolerance – and Professor Calliope Dendrou, from the University of Oxford, an expert in immune disease single-cell and spatial multiomics.

Professor Anderson commented: “By revealing how immune cells interact with tissue during chronic inflammation, our goal is to find a way of using these Regulatory T-cells as a naturally occurring way of treating autoimmune disease of the liver – nature’s medicine. We aim to use our work as proof of concept in the liver that is transferrable to other forms of the condition which can cause significant damage to the gut, skin, and other organs.”

Professor Sakaguchi was awarded an honorary Doctor of Science degree by the University of Birmingham in 2019 in recognition of his vision and research driving the development of regulatory T cells as therapeutic in autoimmunity and organ transplantations.

Professor Shimon Sakaguchi following the award of his honorary Doctor of Science degree in 2019 – pictured with the University’s then Pro-Chancellor Ed Smith CBE (left) and former Head of College of Medicine and Health Professor David Adams. (Photo: Paul Bonning-Tyers from Ede and Ravenscroft)

New funding set to improve discharge of pancreatitis patients

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

Birmingham researchers have won funding to develop recommendations to save acute pancreatitis patients returning to hospital and find ways to support patients following discharge, including long-term conditions such as mental health and diabetes, and reduce health service use.

Acute pancreatitis is a common condition leading to approximately 40,000 people being admitted to hospitals each year in the UK. This inflammation of the pancreas causes symptoms including pain, nausea and vomiting, and severe cases of the condition can be life-threatening. Currently, recommendations for post-discharge support are limited, and around 10% of patients will be readmitted within 30 days.

After being discharged from hospital, some patients continue to have health issues because their pancreas struggles to digest food or manage blood sugar. Half of those affected by acute pancreatitis may be at risk of developing mental health issues, such as anxiety or depression.

The PANORAMA project led by surgeon and researcher Matthew Lee, expands the University of Birmingham’s extensive National Institute of Health and Social Care Research (NIHR) funded portfolio to the value of almost £1million and will run for the next three years. He said: “Patients tell us that they feel left on their own after hospital discharge following pancreatitis. This work will help us figure out we can better manage follow up, and help people to look after themselves in the community.”

Lee and team will produce high quality evidence about the accessibility, acceptability, and costs of support, care and treatments in current post-hospital pathways for people with acute pancreatitis. In a series of surveys, interviews and workshops, bringing together patients and healthcare professionals, they will determine recommendations for changes to current pathways.

The need for research in this area was highlighted by the James Lind Alliance and the study has been designed by patients, nurses, primary care and hospital doctors, as well as experts in health service research.

It is hoped the recommendations will benefit acute pancreatitis patients, families and lead to savings for the health service.

Matthew is a Clinician Scientist with the University of Birmingham, and is also an Honorary Consultant Colorectal Surgeon at University Hospitals Birmingham – both founding members of BHP.

Possible new disease targets for children with arthritis revealed by first-of-its-kind study

Written by Louise Stanley on . Posted in Experimental medicine, Inflammation and chronic disease.

Groundbreaking research by a team from BHP’s Birmingham Children’s Hospital and the University of Birmingham – working with UCL and Great Ormond Street Hospital – has revealed important clues into what is driving disease in children with arthritis.

Cutting-edge techniques have allowed scientists to uncover the unique architecture of cells and signals inside the joint as inflammation takes hold, for the first time.

Published in Science Translational Medicine, the study investigated juvenile idiopathic arthritis in children – caused by the immune system mistakenly attacking joints – which affects more than 10,000 children in the UK. It causes swelling, stiffness and pain in the joints over years or decades, leading to damage of the joints and long-term disability. While there are pain management treatments available, which in some cases achieve remission, there is no cure – and it can take time to find which treatment works for each person. Treatments don’t work in the same way for every child, suggesting there are hidden differences between individuals that we are yet to fully understand.

Deepening the scientific and clinical community’s understanding of the condition is vital if more effective treatments are to be found, and undertaking biopsies in young children provides a new way forward. The study’s potential has been advocated for by families of children with arthritis, who agreed that the procedure would be acceptable to families, especially compared to living with a chronic inflammatory disease.

In a world first, tiny tissue samples were collected from the joint lining when children were having medicine injected into the joint, which were then analysed with advanced imaging and gene-profiling technologies. The fine resolution maps of the joints revealed differences between children of different ages and cell changes in those with more severe disease – creating unique cellular ‘fingerprints’ which may help researchers understand why some drugs work better for some children, and not others. The joints of children with arthritis also looked significantly different to those with adults, demonstrating the need to understand arthritis in children better.

Mapping out the networks of cells in the joint revealed a barrier layer (pink), with immune cells (navy) flooding in through blood vessels (light blue), which increase in number as the disease continues

Professor Adam Croft, Versus Arthritis Professor of Rheumatology at the University of Birmingham and chief investigator of the study, said: “We know how frustrating it can be for families and young people to find a drug that best works for their arthritis. Finding ways to better predict which medicines will be beneficial for a particular child would mean we were able to treat the disease more rapidly and effectively. To achieve this goal, we first needed to understand what cells make-up the lining of the joint where the inflammation occurs. Equipped with that knowledge, we can now start to tackle the next challenge, determining how these cellular fingerprints within the joint tissue can help us predict which drug will work best, ensuring we give the right drug, to the right child, at the right stage of their disease.”

Professor Lucy Wedderburn, University College London Great Ormond Street Institute of Child Health and Consultant of Paediatric Rheumatology at Great Ormond Street Hospital said: “This study represents a real step change in our work with children and young people who live with arthritis, and has been a huge team effort. Rather than having to rely on blood tests which often do not tell us accurately what is happening in the joint, we can now directly analyse the joint lining, across different types of childhood arthritis and different ages. Our findings show that younger children have different types of immune cells invading their joints compared to older children. Samples from children with arthritis looked different to adult samples, with a different make up of immune cells, blood vessels and distinct connective tissue cells. This suggests that treatments may need to vary depending on age and shows why we can’t just extend studies from adult studies to understand arthritis in children.”

The study was funded by the Medical Research Council, Versus Arthritis, National Institute of Health and Care Research, Great Ormond Street Hospital Charity, amongst others, and delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC).

Instrumental to driving this research forward was Dr Eslam Al-Abadi, a study investigator from the Birmingham Women’s and Children’s Hospital NHS Foundation Trust, who sadly passed away before publication. His incredible efforts in seeking to improve the care of children with this disease are gratefully acknowledged.

Promising new steroid drug could offer safer arthritis treatment

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

Early research has found that a new steroid drug, used for treating Duchenne Muscular dystrophy, has shown significant promise in treating inflammatory diseases such as rheumatoid arthritis.

Research published in Rheumatology revealed that Vamorolone, a glucocorticoid, showed to be just as effective as standard glucocorticoids to treat inflammation but with minimised negative side effects.

Glucocorticoids are some of the most widely used drugs to treat patients with a diverse range of inflammatory diseases. Unfortunately, whilst they effectively reduce inflammation and pain, they can also cause severe side effects. These include muscle and bone loss that can increase the risks of falls and fractures.

Vamorolone is a unique metabolism-resistant steroid approved by the FDA which appears to provide significant anti-inflammatory benefits while causing fewer harmful effects on muscle and bone.

The study, funded by the Foundation to Eradicate Duchenne and utilising mouse models with chronic rheumatoid arthritis, shows Vamorolone could be a promising alternative treatment for patients living with the disease.

Dr Rowan Hardy, Associate Professor in Steroid Metabolism and Signalling at BHP founder-member the University of Birmingham, said: “If Vamorolone is effective in patients with rheumatoid arthritis, it would allow us to better control disease activity, whilst preserving muscle and bone to reduce the risks of fractures and falls.”

The study team have now secured further funding with the Foundation to Eradicate Duchenne that will allow the research team to better understand the processes whereby Vamorolone is able to protect muscle and bone in patients with inflammatory disease. 

Through their involvement with the Birmingham Rheumatology group under Professor Adam Croft, and the NIHR Birmingham Biomedical Research Centre’s Inflammatory Arthritis Theme, the team will now work with clinicians to examine the possibility for new clinical trials to examine Vamorolone in rheumatoid arthritis patients. 

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Birmingham teenager first in UK to receive groundbreaking diabetes treatment

Written by Louise Stanley on . Posted in Birmingham Health Partners, Early diagnosis and detection, Inflammation and chronic disease.

A young patient identified by the ELSA study as having early stages of Type 1 Diabetes, has received treatment to delay the condition.

Sam, aged 14 and from Kings Norton, was the first to receive the new drug, Teplizumab, at the Clinical Research Facility at Birmingham Children’s Hospital.

Sam’s dad, Chris, has Type 1 diabetes and knowing that family members are more likely to develop the disease, Sam was screened for early stages of the condition and learnt he would develop Type 1 Diabetes. However, there was good news for the family when Sam was offered Teplizumab, a new treatment to delay the onset of the chronic illness. Past trials have proven that Teplizumab delays insulin-dependent diabetes for up to three years.

Sam’s mum, Louise, explained: “I know from Sam’s dad just how stressful life with Type 1 Diabetes is, having to constantly monitor your blood sugar and carry insulin with you at all times. We’re so happy that Sam doesn’t have to worry about his blood sugar yet, especially while he is doing his GCSEs. He can just be a normal teenager.”

Teplizumab is prescribed on a case-by-case basis for children who have been recently diagnosed with type 1 diabetes and are at early stages.

Dr Renuka Dias, a researcher from University of Birmingham’s Department of Applied Health Sciences and Consultant Paediatric Endocrinologist working at Birmingham Women’s and Children’s Hospital, said: “Being able to delay insulin-dependent diabetes will have a huge impact on a child’s life. It means we are letting children have a normal childhood for much longer.”

Dr Dias and her specialist team at the Clinical Research Centre who were involved in Sam’s care have also been integral to a first-of-its-kind study, led by the University of Birmingham, to screen children aged 3 to 13 to find out their risk of developing type 1 diabetes. The study aims to allow treatment to begin sooner and, as in Sam’s case, delay the start of the condition.

The ELSA study has screened over 20,000 children in the UK for Type 1 Diabetes in the last two years. The study is now scaling up throughout Europe.

Unfortunately, it often takes a child becoming seriously unwell for a diagnosis of Type1 Diabetes to be made. Through the study, families identified with a child who is at-risk can begin educating themselves about the condition and learning about the options for management before they find themselves in that crisis situation.

Support and education has been made available to study participants. In addition, some children, like Sam, will be eligible to explore treatment options that could delay the onset of the condition.

Parth Narendran, Professor of Diabetes Medicine at the University of Birmingham and lead for the Type 1 Diabetes clinical service at the Queen Elizabeth Hospital Birmingham (QEHB), said: “We hope that the ELSA study will lead to the roll-out of Type 1 Diabetes early detection programme for children in the UK and that many more children could then benefit from potential treatments to delay Type 1 Diabetes in future.”

Birmingham Women’s and Children’s Hospitals, the University of Birmingham, and University Hospitals Birmingham – which operates QEHB – are founder-members of Birmingham Health Partners. Fellow BHP members Birmingham Community Healthcare NHS Foundation Trust is an ELSA Study partner.

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Aston University and Birmingham Children’s Hospital study shows diagnosis and treatment of preschool wheeze needs improvement

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

A study led by Aston University’s Dr Gemma Heath and  Dr Prasad Nagakumar from Birmingham Children’s Hospital – both BHP member organisations – has shown that treatment and diagnosis for preschool wheeze needs more effective evidence-based guidelines.

Preschool wheeze affects approximately 30–40% of children under six. The condition is characterised by episodes of wheezing or breathlessness, with younger children being particularly susceptible due to their narrower airways. Although it can resemble asthma, preschool wheeze is often triggered by viral infections or allergies and does not always mean a child will develop asthma.

The UK has Europe’s second highest prevalence of preschool wheeze in two-year-olds and is a leading cause of emergency hospital visits and hospitalisations in the country. Repeated preschool wheeze attacks are frightening for parents, and result in significant morbidity, healthcare costs and impaired quality of life for both the child and parent.

There is currently no diagnostic pathway or definitive management guidelines for preschool wheeze. The research team interviewed affected parents and carers about their experiences, and found problems with diagnosis and treatment at multiple levels.

The first major issue identified by parents was inconsistent terminologies used by doctors, and confusing and conflicting diagnoses such as asthma, suspected asthma, viral wheeze and allergy. Some reported frustration at the lack of definitive diagnosis, an apparent lack of GP knowledge, sometimes false reassurance that the wheeze was viral rather than asthma, or that the cause was a “mystery”.

A common problem was that investigative tests did not occur until after multiple hospitalisations. Blood tests for particular markers have potential to identify whether asthma or an allergy is likely to have caused the wheeze, and therefore guide treatment. The parents in the study welcomed the idea of timely tests, but stressed that children should not be subjected to repeated testing.

Preschool wheeze is generally managed with steroid and salbutamol inhalers, as for asthma. While parents had concerns about the side-effects and long-term impacts of using the treatments, they deemed the medication “an acceptable cost”.

Parents reported being “terrified” while watching attacks of preschool wheeze, and significant psychological impacts when their child was admitted to hospital. Some had missed work or even given up work to care for their child, with high levels of anxiety, while others said they felt unable to go on holiday overseas due to concerns about healthcare access in the case of a wheeze attack.

Most parents preferred to access care at hospital rather that at doctors’ surgeries due to the perception of a lack of training for GPs and a lack of confidence. However, accessing necessary care can be difficult, including due to childcare difficulties, the cost of hospital parking and a lack of available ambulances.

The research team said that parents’ views highlight the problems and called for clinical trials to determine the efficacy of treatment decisions made according to the results of investigations.

Dr Heath said: “This research demonstrates an urgent need for preschool wheeze management policies and treatment pathways that are evidence-based and co-developed with parents. We have shown that use of investigations such as blood or allergy tests would be acceptable to parents, if they were shown to be helpful in guiding more effective and timely treatments.”

Dr Nagakumar said: “Preschool wheeze has significant impact on young children’s and their parents’ lives. Our research, involving parents with lived experience, will inform future studies to improve the care and reduce the impact of preschool wheeze on the already-stretched emergency health services in the UK.”

Archives of Disease in Childhood doi: 10.1136/archdischild-2024-327781