Free public event on our latest inflammation research

WHERE: Hexagon Room, Frank Lee Centre, Cambridge Biomedical Campus

Inflammation is an essential part of how we fight off infection. However, sometimes it persists even after an infection clears, happens in the wrong place or kicks off even without any signs of infection – and results in a range of health conditions that reduce quality of life for patients.

Join us for an hour of talks either in the afternoon (4-5pm) or evening (6-7pm) on the latest developments in inflammation research at NIHR Cambridge BRC and take the opportunity to chat with local researchers about their research.

Whether you choose to come for the afternoon or evening talks, you are welcome to spend the hour from 5-6pm chatting to our researchers about their work and view the research posters on display. Why not vote for your favourite poster while enjoying some light refreshments?

Our speakers

• Dr. Bina Patel, Clinical Research Fellow, Department of Clinical Neuroscience at the University of Cambridge
• Prof. Menna Clatworthy, NIHR Cambridge BRC Theme Lead for Immunity, Inflammation and Transplantation and Professor of Translational Immunology, University of Cambridge
• Prof. Clare Elizabeth Bryant, Professor of Innate Immunity, Department of Medicine at the University of Cambridge

Book your preferred session

You only need to book one session to attend the talks and poster exhibition, as the talks are the same for the afternoon and evening slots: and you are welcome to stay for some or all of the hour (5-6pm) between talks to chat to researchers, view the posters and enjoy light refreshments.

• To book the afternoon session from 4-5pm: visit https://bit.ly/InflamAFTER
• To book the evening session from 6-7pm: visit https://bit.ly/InflamEVE

Questions?

If you have any questions either before or after you book your ticket, please contact Georgina Norris via email: gan23@cam.ac.uk.

Global spotlight on Cambridge heart trial

Results of an NIHR Cambridge BRC and NIHR Cambridge CRF supported trial which may help prevent patients from having repeat heart attacks, will be presented at the 30^th European Society of Cardiology (ESC) Congress, the largest cardiology conference globally.

The IVORY and IVORY FINALE trial looked at whether a low dose of the cancer drug, known as aldesleukin, could increase the activation of immune cells shown to protect the heart and help patients who have had a heart attack.

Current treatment for heart attacks centres on the re-establishment and maintenance of blood flow in the coronary arteries using blood thinners, with or without stents, as well as cholesterol lowering medication. Despite current optimal therapy, heart attacks can re-occur.  

The team believes the immune system is an important process in the development of atherosclerosis (plaque disease in arteries) which has not been directly harnessed in these patients and attempted to target it using a novel approach.

The researchers found in a previous trial that low doses of aldesleukin, a drug normally used to treat kidney cancer (at much higher doses), stimulates the production of protective immune cells, called Tregs safely in patients with heart attacks.

In the current trial, they tested to see if the drug reduced inflammation in the arteries of patients after an initial heart attack, as inflammation in the arteries has previously been associated with an increase in the risk of recurrent heart attacks and death.

The study was led by researchers at Cambridge University Hospitals (CUH) and the University of Cambridge (UofC) as well as Royal Papworth Hospital, and was supported by the Medical Research Council, the British Heart Foundation, the NIHR Cambridge Biomedical Research Centre and the NIHR Cambridge Clinical Research Facility.

The results will be unveiled at the ‘late-breaking’ sessions of the 30^th European Society of Cardiology (ESC) Congress 2024 in London on 30 August and will be presented by Dr Rouchelle Sriranjan, an interventional cardiology registrar and NIHR clinical lecturer in cardiology, pictured right.

CUH consultant clinical pharmacologist, affiliated associate professor and trial chief investigator, Dr Joseph Cheriyan, said: “We are delighted to be presenting these novel data at the ESC and particularly in the late breaking session, which is a highlight of the conference.

“This study was the product of very intense work by many different teams on the campus in very sick patients and demonstrates the importance of collaborative teamwork. We are very grateful to the patients for their time and dedication to our trial.”

Dr Stephen Hoole was the trial lead for Royal Papworth Hospital, whilst Professor Rudd led the imaging component for the trial.

Professor Ziad Mallat, BHF professor of cardiovascular medicine, UofC, who conceived the trial said: “If positive, this is potentially a new treatment approach that boosts our immune defence mechanisms to tame heart attacks. It could also be an important step forward in the treatment of patients with heart attacks which needs continued exploration.

“Our results should be of interest to the wider cardiovascular community. In addition to our supporters and funders, we would like to thank everyone who has worked so hard on the trial, especially the patients who have taken part.”

Cambridge professor receives top award for outstanding research in endocrinology

Congratulations to Krishna Chatterjee, Director of the NIHR Cambridge Clinical Research Facility and Professor of Endocrinology at the University of Cambridge, who has been awarded the Gerald D. Aurbach Award for Outstanding Translational Research from the Endocrine Society.

Prof Chatterjee is one of 14 leading endocrinologists who were selected for the Society’s prestigious 2025 Laureate Awards, which recognise the highest achievements in endocrinology research and care, and which are regarded as the highest honours in the field.

Prof Chatterjee was awarded for his research on genetic and molecular endocrinology, exploring disorders including resistance to thyroid hormone and PPARgamma gene defects associated with lipodystrophic insulin resistance.

He said: “It is a privilege to accept this award which also represents the efforts of many clinical and scientist colleagues as well as patients taking part in our research, without whom our contributions to advancing knowledge and changing health outcomes in endocrine disorders would not have been possible.”

The Endocrine Society will present the awards to the winners at ENDO 2025, the Society’s annual meeting, being held next July 12-15 in San Francisco.

The role of a SAB and why it’s important

A personal reflection from Professor Miles Parkes, Director of NIHR Cambridge Biomedical Research Centre (BRC)

Every two years something very special happens in the life of the NIHR Cambridge BRC – and it’s something we all look forward to hugely.

It’s when our international Scientific Advisory Board (or SAB) of leaders in biomedical research join us over two days as ‘critical friends’, to hear about our early translational research (research fresh from the laboratory, exploring how it can be applied in people to sustain health and treat disease), review its quality and provide strategic direction.  The meeting also provides an opportunity for us and our partners to come together to celebrate our successes and take a critical look at ourselves. This whole process is crucial, not only for our governance, but to hold us accountable for the research we do. 

In April this year, meeting in the Cancer Research UK Cambridge Institute, I welcomed our SAB and a large audience with a brief introduction to the biomedical campus with its rich inter-digitation of healthcare, research, and industry facilities. The BRC plays a key role in supporting early translational research infrastructure, enabling projects led by our investigators and their partners. Many of these projects involve extensive collaborations and reach beyond the campus to our region and nationally.

After my introduction I handed over to the leads of our 13 research themes for a sequence of presentations on their ground-breaking research and its impact.  Their emphasis is absolutely on priorities identified by patients, and how our research can best address their concerns and health priorities. None of our research would happen without patients – and so we had talks on our patient and public involvement and equality and diversity work, and an opportunity for the SAB and others to see first-hand the new Clinical Research Facility (a place for participants to take part in research) in the Victor Phillip Dahdaleh Heart and Lung Research Institute.

Over two days, we enjoyed lots of opportunities to ask questions and give feedback – including where we can improve. There was lots of thought-provoking discussion about the direction of research and how we can develop new diagnostics and treatments for some of our biggest health challenges.

Having an event like this is critical to our work – highlighting the successes but also providing an opportunity for constructive criticism.  I was delighted to see the SAB members so engaged, see so many staff in the audience – and receive so many positive comments regarding the important research we do in Cambridge.

But please don’t just take my word for it: watch our short video and hear for yourself why our attendees think that our biomedical campus supported by the NIHR Cambridge BRC is a special place to conduct health research.

Patient and Public Involvement week returns and is a huge hit

Nearly 200 people attended an exciting week of Patient and Public Involvement events at the end of June. This was the first event of its kind held on the Cambridge Biomedical Campus.

Hosted by the NIHR Cambridge Biomedical Research Centre (BRC), University of Cambridge and Anglian Ruskin University (ARU), the event aimed to celebrate and raise awareness of Patient and Public Involvement (PPI) in health research.

The week began with a webinar for members of the public who were able to hear how people’s voices can help shape health and care research and opportunities to get involved in research through CUH, NIHR Cambridge BRC, Anglia Ruskin University and other health and research partners across the region. The 90-minute webinar highlighted the importance of PPI in health research and attendees heard about some of the examples of activities the NIHR Cambridge BRC PPI panel members are involved in.

On Tuesday we held a public PPI showcase of talks and poster exhibits from health researchers where they explained how patient and public involvement had made an impact to their research. Attendees were able to network and vote for the best poster and talks from the morning and afternoon sessions. The all-day event received excellent feedback, with one saying: “I just wanted to give a big thank you. It’s really important to have an event where you can find out about what is going on in Cambridge and the PPI space.”

Wednesday provided an opportunity to learn from our partners at ARU about their ‘Let’s Shape Research Together’ public involvement programme. Their annual conference showcases case studies, as well as keynote speakers from PPIE experts across Cambridgeshire.

The final event of the week was a market stall drop-in at the David Dunn Suite in CUH, where staff and members of the public could meet health and research patient and public involvement teams across Cambridgeshire, from the NIHR Cambridge BRC, Cambridge Biomedical Campus local voices, CRUK, IMS and Stem Cell, Cambridge School of Biology, Cambridge Clinical School, Cambridge Children’s Hospital, ACTIVE and CUH members. The organisations were able to provide more information on how people could volunteer to their panels and offer staff support and advice on their PPI projects. One attendee said: “It was a great event, I had some really valuable conversations with the staff.”

Dr Amanda Stranks, PPI and communications strategy lead from NIHR Cambridge BRC and one of the organisers said: “This week of PPI events gave us the chance to celebrate and showcase some of the best examples of patient and public involvement in research that are happening on the Cambridge Biomedical Campus. The variety and quality of the examples are testament to how researchers and our public are working in partnership across Cambridge to produce life-changing research.

“Patient and Public Involvement makes such a difference to the research we do here in Cambridge. We need public voices to make sure we are doing the best research we can, and that our research opportunities are widely accessible and meet patient’s needs. Showcasing examples of how the public make a different to our research and our researchers helps to encourage more researchers and members of the public to get involved.

“We’re really pleased by the response of staff and the public to the week’s activities and would like to extend our thanks to all who came and supported the events. We received some amazing feedback and are delighted to see an increase in sign-ups to some of the Cambridgeshire panels. We’re looking forward to seeing everyone next year, for an even bigger regional public involvement week!

Read about the three winners from the PPI showcase as voted by attendees.

Winners announced for 2024’s Cambridge PPI showcase event

Improving women’s access to pelvic health services, using drama and theatre to help interpret genetic data research and public engagement with paediatric Inflammatory Bowel Disease were all winners at the 2024 Cambridge Patient and Public Involvement (PPI) showcase.

Jointly hosted by the NIHR Cambridge BRC (BRC) and the University of Cambridge, more than 115 members of the public, researchers and healthcare staff attended a showcase of how patient and public involvement (PPI) has impacted our Cambridge research.

The day was split into three sessions of morning and afternoon talks and a poster exhibition over lunch, with a chance to network with researchers. Attendees were then able to vote for their favourite poster and talk from each session, with the winners receiving a certificate and £50 gift voucher.

Improving disadvantaged women’s access to pelvic healthcare

The winning talk from the morning session was awarded to Claire Brown, pre-doctoral research fellow and pelvic health physiotherapist at Cambridge University Hospitals, pictured left, and Dr Caroline Zwierzchowska-Dod, Strategic Lead, Cambridgeshire and Peterborough Maternity and Neonatal Voices. Their research focused on whether women in under-served communities were able to access pelvic health services and how much information they had received about pelvic floor dysfunction during their pregnancy.

Claire and Caroline worked with leaders from a range of community groups on how best to approach women to take part. This led to a series of listening events with an ethnic minority mothers’ group, a Gypsy-Roma-Traveller (GRT) community and with asylum seekers living in Government accommodation. In total 18 women attended to share their ideas, questions and experiences.

Claire and Caroline found most women had not received enough information on the risks of developing pelvic floor dysfunction during pregnancy and were therefore less likely to recognise their symptoms in order to find support or treatment. The women preferred to speak to their GP or midwife, but these clinical teams may not have specific expertise to help manage the condition effectively. Most of the women that Claire and Caroline spoke to also said they were unaware that there were self-referral options for pelvic health physiotherapy.

From these sessions Claire and Caroline were able to create a leaflet, including an easy read format, of pelvic floor muscle exercises and post-caesarean advice for healthcare staff in hospitals and the community to give to their patients and make them more aware of the disorder.

Claire said: “I have been very lucky to be able to work with Caroline, thanks to a PPIE innovation grant from the NIHR CRN East of England, which covered the costs of these listening events. We have discovered invaluable information and acted on this to improve the access to pelvic health services, this is just the beginning of this journey. I am so pleased we have been able to build strong relationships with community leaders for future work.”

Playing with Genetic data

The winning talk from the afternoon session was awarded to Dr Amy Mason, research associate in cardiovascular disease, pictured left. Amy’s talk explained the challenges in talking with the public about her research using genetic data to predict whether someone was at a potential risk of cardiovascular disease (conditions that affect the heart) in the future.

Amy worked with Cambridge Creative Encounters and local theatre group Babolin Young Company to develop two short fictional plays about whether knowing about being at risk of a condition could change a patient’s lifestyle and environmental behaviours.

The PPI group, made up of diverse representatives, reviewed the plays and information sheets to create a discussion about genetic risk scores. The plays helped the panel to explore the topic much more personally and reflectively, rather than just looking at facts, data and statistics. The drama helped the participants to come up with questions, such as whether the data was accurate, does it help patients and is that knowledge worthwhile? They also discussed how precise genetic risk scores are and how the data sets are collected. The health data could be different for each diverse group and it wouldn’t necessarily mean a ‘one size fits all’.

Amy found that using more creative outputs such as plays helped improve conversations and was an effective way of getting key messages across.

Amy said: “I really loved working with our PPIE volunteers with creative arts. I found talking about fictional narratives with the panel made me more confident to bring up my own concerns and questions. The panel’s responses really changed how I prioritise and approach research questions.”

You can watch the plays at 57:40 minutes in , there is also a short documentary about creative encounters behind the curtains.

Driving inclusivity with IBD

There were 12 posters on display during the lunchtime exhibition and attendees voted for research nurse, Claire Glemas, pictured right, from the Cambridge Stem Cell Institute as the poster winner.

Claire’s poster highlighted her PPI work with children with Inflammatory Bowel Disease (IBD), particularly focusing on understanding their lived experiences. By working with a group of children and young people, she wanted to see where improvements could be made with the patient’s experience during their clinic appointments and when taking part in research.

Over three years, Claire and a PPI group of children and young people developed a number of engagement opportunities including a quarterly gastroenterology newsletter, co-designed and edited with a member of the group. They hosted a Young Scientist day where children can come and see the labs and work as research assistants, and an annual family day with research, hospital staff and volunteers. Patients were given access to IBDmate, an educational tool about IBD, and an interactive colouring journal to help with their treatment pathway.

In her poster, Claire demonstrates the importance of communicating effectively with patients and their parents. She hopes that her engagement work with the children’s group will help new patients and their families understand IBD and make informed decisions about their health and when taking part in research. It has created an engaged community of staff and patients working together to improve healthcare services for young patients with IBD. 

Claire said: “Our patient community will ensure every aspect of our research is shaped by the perspective and voices of our patients and families. We are committed to our mission, building PPI into an integral part of what we do, gathering invaluable insights and ultimately driving improvement in our research.”

The PPI Showcase was the first on the Cambridge Biomedical Campus, with more than 25 talks and posters highlighting how PPI makes a difference in local research. Dr Amanda Stranks, PPI and communications strategy lead for the NIHR Cambridge BRC who led the event said: “The PPI showcase was a wonderful opportunity to show researchers and the public how PPI has shaped our research and made a positive impact in the way we deliver our studies. There was such a variety of examples on display, demonstrating the importance of PPI and how it makes a difference. We’re looking forward to making this an annual event, to encourage more people to get involved in our research!’

Georgina Norris, PPI coordinator for the NIHR Cambridge BRC and event organiser said: “We were overwhelmed with the number of abstracts we received for people who wanted to take part, so we know there truly is some amazing PPI work happening across Cambridge.

“All the talks and posters on the day were brilliant but sadly we could only award one person from each session. I’d like to thank everyone who presented their PPI work, all our attendees and everyone who has contributed to our research, we couldn’t do it without you.”

Artificial intelligence outperforms clinical tests at predicting progress of Alzheimer’s disease

Cambridge scientists have developed an artificially-intelligent tool capable of predicting in four cases out of five whether people with early signs of dementia will remain stable or develop Alzheimer’s disease.

The team say this new approach could reduce the need for invasive and costly diagnostic tests while improving treatment outcomes early when interventions such as lifestyle changes or new medicines may have a chance to work best.

Dementia poses a significant global healthcare challenge, affecting over 55 million people worldwide at an estimated annual cost of $820 billion. The number of cases is expected to almost treble over the next 50 years.

The main cause of dementia is Alzheimer’s disease, which accounts for 60-80% of cases. Early detection is crucial as this is when treatments are likely to be most effective, yet early dementia diagnosis and prognosis may not be accurate without the use of invasive or expensive tests such as positron emission tomography (PET) scans or lumbar puncture, which are not available in all memory clinics. As a result, up to a third of patients may be misdiagnosed and others diagnosed too late for treatment to be effective.

A team led by scientists from the Department of Psychology at the University of Cambridge has developed a machine learning model able to predict whether and how fast an individual with mild memory and thinking problems will progress to developing Alzheimer’s disease. In research published today in eClinical Medicine, they show that it is more accurate than current clinical diagnostic tools.

To build their model, the researchers used routinely-collected, non-invasive, and low-cost patient data – cognitive tests and structural MRI scans showing grey matter atrophy – from over 400 individuals who were part of a research cohort in the USA.

They then tested the model using real-world patient data from a further 600 participants from the US cohort and – importantly – longitudinal data from 900 people from memory clinics in the UK and Singapore.

The algorithm was able to distinguish between people with stable mild cognitive impairment and those who progressed to Alzheimer’s disease within a three-year period. It was able to correctly identify individuals who went on to develop Alzheimer’s in 82% of cases and correctly identify those who didn’t in 81% of cases from cognitive tests and an MRI scan alone.

The algorithm was around three times more accurate at predicting the progression to Alzheimer’s than the current standard of care; that is, standard clinical markers (such as grey matter atrophy or cognitive scores) or clinical diagnosis. This shows that the model could significantly reduce misdiagnosis.

The model also allowed the researchers to stratify people with Alzheimer’s disease using data from each person’s first visit at the memory clinic into three groups: those whose symptoms would remain stable (around 50% of participants), those who would progress to Alzheimer’s slowly (around 35%) and those who would progress more rapidly (the remaining 15%). These predictions were validated when looking at follow-up data over 6 years. This is important as it could help identify those people at an early enough stage that they may benefit from new treatments, while also identifying those people who need close monitoring as their condition is likely to deteriorate rapidly.

Importantly, those 50% of people who have symptoms such as memory loss but remain stable, would be better directed to a different clinical pathway as their symptoms may be due to other causes rather than dementia, such as anxiety or depression.

Senior author Professor Zoe Kourtzi from the Department of Psychology at the University of Cambridge said: “We’ve created a tool which, despite using only data from cognitive tests and MRI scans, is much more sensitive than current approaches at predicting whether someone will progress from mild symptoms to Alzheimer’s – and if so, whether this progress will be fast or slow.

“This has the potential to significantly improve patient wellbeing, showing us which people need closest care, while removing the anxiety for those patients we predict will remain stable. At a time of intense pressure on healthcare resources, this will also help remove the need for unnecessary invasive and costly diagnostic tests.”

While the researchers tested the algorithm on data from a research cohort, it was validated using independent data that included almost 900 individuals who attended memory clinics in the UK and Singapore. In the UK, patients were recruited through the Quantiative MRI in NHS Memory Clinics Study (QMIN-MC) led by study co-author Dr Timothy Rittman at Cambridge University Hospitals NHS Trust and Cambridgeshire and Peterborough NHS Foundation Trusts (CPFT).

The researchers say this shows it should be applicable in a real-world patient, clinical setting.

Dr Ben Underwood, Honorary Consultant Psychiatrist at CPFT, assistant professor at the Department of Psychiatry, University of Cambridge and NIHR Cambridge BRC researcher, said: “Memory problems are common as we get older. In clinic I see how uncertainty about whether these might be the first signs of dementia can cause a lot of worry for people and their families, as well as being frustrating for doctors who would much prefer to give definitive answers. The fact that we might be able to reduce this uncertainty with information we already have is exciting and is likely to become even more important as new treatments emerge.”

Professor Kourtzi said: “AI models are only as good as the data they are trained on. To make sure ours has the potential to be adopted in a healthcare setting, we trained and tested it on routinely-collected data not just from research cohorts, but from patients in actual memory clinics. This shows it will be generalisable to a real-world setting.”

The team now hope to extend their model to other forms of dementia, such as vascular dementia and frontotemporal dementia, and using different types of data, such as markers from blood tests.

Professor Kourtzi added: “If we’re going to tackle the growing health challenge presented by dementia, we will need better tools for identifying and intervening at the earliest possible stage. Our vision is to scale up our AI tool to help clinicians assign the right person at the right time to the right diagnostic and treatment pathway. Our tool can help match the right patients to clinical trials, accelerating new drug discovery for disease modifying treatments.”

The study was funded by Wellcome, the Royal Society, Alzheimer’s Research UK, the Alzheimer’s Drug Discovery Foundation Diagnostics Accelerator, the Alan Turing Institute, and the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Paper:

Lee, LY & Vaghari, D et al. Robust and interpretable AI-guided marker for early dementia prediction in real-world clinical settings. eClinMed; 12 July 2024; DOI: 10.1016/j.eclinm.2024.102725

Researcher awarded prestigious Academy of Medical Sciences Fellowship

Congratulations to Professor Nita Forouhi, NIHR Senior Investigator and co-theme lead for Nutrition, Obesity, Metabolism and Endocrinology, who has been elected as a fellow of the Academy of Medical Sciences.

Professor Forouhi’s work focuses on nutritional epidemiology and finding modifiable factors for the prevention of type 2 diabetes and related metabolic disorders.

The Academy of Medical Sciences is the independent, expert body representing the diversity of medical science in the UK. Its mission is to advance biomedical and health research and its translation into benefits for society. The Academy’s elected Fellows are the most influential scientists in the UK and worldwide, drawn from the NHS, academia, industry and the public service. 

In total the academy has recognised 58 scientists for this year’s award. They were selected for their outstanding contribution and discoveries to biomedical and health sciences.

Professor Andrew Morris PMedSci, President of the Academy of Medical Sciences, said: “It is an honour to welcome these brilliant minds to our Fellowship. Our new Fellows lead pioneering work in biomedical research and are driving remarkable improvements in healthcare. We look forward to working with them, and learning from them, in our quest to foster an open and progressive research environment that improves the health of people everywhere through excellence in medical science.  

“It is also welcoming to note that this year’s cohort is our most diverse yet, in terms of gender, ethnicity and geography. While this progress is encouraging, we recognise that there is still much work to be done to truly diversify our Fellowship. We remain committed to our EDI goals and will continue to take meaningful steps to ensure our Fellowship reflects the rich diversity of the society we serve.” 

Read the full list of this years of elected scientists.

The new Fellows will be formally admitted to the Academy on Wednesday 18 September 2024. 

Cambridge researchers elected as Fellows of the Royal Society 2024

Congratulations to our NIHR Cambridge BRC researchers who have been elected as Fellows of the Royal Society, the UK’s national academy of sciences.

More than 90 researchers from around the world have been elected as Fellows of the Royal Society and have been recognised for their invaluable contributions to science.

This year’s list included four NIHR Cambridge BRC researchers, (pictured left to right):

Professor Sarah-Jayne Blakemore, Professor of Psychology and Cognitive Neuroscience, from the NIHR Cambridge BRC Mental Health theme.

Professor Rebecca Fitzgerald, Professor of Cancer Prevention and Director, Early Cancer Institute and Devices and Advanced Therapies NIHR Cambridge BRC theme lead.

Professor Patrick Chinnery, Professor of Neurology, Department of Clinical Neurosciences, from the NIHR Cambridge BRC Neurosciences theme.

Professor George Malliaras, Professor of Technology, Department of Engineering, University of Cambridge, from the NIHR Cambridge BRC Devices and Advanced Therapies theme.

Sir Adrian Smith, President of the Royal Society, said: “I am pleased to welcome such an outstanding group into the Fellowship of the Royal Society.

“This new cohort have already made significant contributions to our understanding of the world around us and continue to push the boundaries of possibility in academic research and industry.

“From visualising the sharp rise in global temperatures since the industrial revolution to leading the response to the Covid-19 pandemic, their diverse range of expertise is furthering human understanding and helping to address some of our greatest challenges.

“It is an honour to have them join the Fellowship.”

Read the full list from the Royal Society.

Baby born deaf can hear after breakthrough gene therapy

A baby girl born deaf can hear unaided for the first time, after receiving ground-breaking gene therapy when she was eleven months old at Addenbrooke’s Hospital in Cambridge.

Opal Sandy from Oxfordshire is the first patient treated in a global gene therapy trial, which shows “mind-blowing” results. She is the first British patient in the world and the youngest child to receive this type of treatment.

Opal was born completely deaf because of a rare genetic condition, auditory neuropathy, caused by the disruption of nerve impulses travelling from the inner ear to the brain.

Within four weeks of having the gene therapy infusion to her right ear, Opal responded to sound, even with the cochlear implant in her left ear switched off.

Clinicians noticed continuous improvement in Opal’s hearing in the weeks afterwards. At 24 weeks, they confirmed Opal had close to normal hearing levels for soft sounds, such as whispering, in her treated ear.

Now 18 months old, Opal can respond to her parents’ voices and can communicate words such as “Dada” and “bye-bye.”

Opal’s mother, Jo Sandy, said: “When Opal could first hear us clapping unaided it was mind-blowing – we were so happy when the clinical team confirmed at 24 weeks that her hearing was also picking up softer sounds and speech. The phrase ‘near normal’ hearing was used and everyone was so excited such amazing results had been achieved.”

Auditory neuropathy can be due to a variation in a single gene, known as the OTOF gene. The gene produces a protein called otoferlin, needed to allow the inner hair cells in the ear to communicate with the hearing nerve. Approximately 20,000 people across the UK, Germany, France, Spain, Italy and UK and are deaf due to a mutation in the OTOF gene.

The CHORD trial, which started in May 2023, aims to show whether gene therapy can provide hearing for children born with auditory neuropathy. The trial in Cambridge is being supported by the NIHR Cambridge Clinical Research Facility and the NIHR Cambridge Biomedical Research Centre.

Professor Manohar Bance, NIHR Cambridge BRC researcher and ear surgeon at Cambridge University Hospitals NHS Foundation Trust who is chief investigator of the trial, pictured left, said: “These results are spectacular and better than I expected. Gene therapy has been the future of otology and audiology for many years and I’m so excited that it is now finally here. This is hopefully the start of a new era for gene therapies for the inner ear and many types of hearing loss.”

Children with a variation in the OTOF gene often pass the newborn screening, as the hair cells are working, but they are not talking to the nerve. It means this hearing loss is not commonly detected until children are 2 or 3 years of age – when a delay in speech is likely to be noticed.

Professor Bance added: “We have a short time frame to intervene because of the rapid pace of brain development at this age. Delays in the diagnosis can also cause confusion for families as the many reasons for delayed speech and late intervention can impact a children’s development.”

“More than sixty years after the cochlear implant was first invented – the standard of care treatment for patients with OTOF related hearing loss – this trial shows gene therapy could provide a future alternative. It marks a new era in the treatment for deafness. It also supports the development of other gene therapies that may prove to make a difference in other genetic related hearing conditions, many of which are more common than auditory neuropathy.”

Mutations in the OTOF gene can be identified by standard NHS genetic testing. Opal was identified as being at risk as her older sister has the condition; this was confirmed by genetic test result when she was 3 weeks old.

Opal was given an infusion containing a harmless virus (AAV1). It delivers a working copy of the OTOF gene and is delivered via an injection in the cochlea during surgery under general anaesthesia. During surgery, while Opal was given the gene therapy in right ear, a cochlear implant was fitted in her left ear.

James Sandy, Opal’s father said: “It was our ultimate goal for Opal to hear all the speech sounds. It’s already making a difference to our day-to-day lives, like at bath-time or swimming, when Opal can’t wear her cochlear implant. We feel so proud to have contributed to such pivotal findings, which will hopefully help other children like Opal and their families in the future.”

Opal’s 24-week results, alongside other scientific data from the CHORD trial are being presented at the American Society of Gene and Cell Therapy (ASGC) in Baltimore, USA this week.

Dr Richard Brown, Consultant Paediatrician at CUH, who is an Investigator on the CHORD trial, said:  “The development of genomic medicine and alternative treatments is vital for patients worldwide, and increasingly offers hope to children with previously incurable disorders. It is likely that in the long run such treatments require less follow up so may prove to be an attractive option, including within the developing world. Follow up appointments have shown effective results so far with no adverse reactions and it is exciting to see the results to date.  

Within the new planned Cambridge Children’s Hospital, we look forward to having a genomic centre of excellence which will support patients from across the region to access the testing they need, and the best treatment, at the right time.”

Martin McLean, Senior Policy Advisor at the National Deaf Children’s Society, said: “Many families will welcome these developments, and we look forward to learning about the long-term outcomes for the children treated. This trial will teach us more about the effectiveness of gene therapy in those cases where deafness has a specific genetic cause.

“We would like to emphasise that, with the right support from the start, deafness should never be a barrier to happiness or fulfilment. As a charity, we support families to make informed choices about medical technologies, so that they can give their deaf child the best possible start in life.”

The CHORD trial is sponsored by Regeneron. Patients are being enrolled in the study in the US, UK and Spain.

Patients in the first phase of the study receive a low dose to one ear. The second phase are expected to use a higher dose of gene therapy in one ear only, following proven safety of the starting dose. The third phase will look at gene therapy in both ears with the dose selected after ensuring the safety and effectiveness in parts 1 and 2. Follow up appointments will continue for five years for enrolled patients, which will show how patients adapt to understand speech in the longer term.

Study highlights increased risk of second cancers among breast cancer survivors

Socioeconomic deprivation linked to greater risk of second cancers among breast cancer survivors

Survivors of breast cancer are at significantly higher risk of developing second cancers, including endometrial and ovarian cancer for women and prostate cancer for men, according to new research studying data from almost 600,000 NHS England patients.

For the first time, the research has shown that this risk is higher in people living in areas of greater socioeconomic deprivation.

Breast cancer is the most commonly diagnosed cancer in the UK. Around 56,000 people in the UK are diagnosed each year, the vast majority (over 99%) of whom are women. Improvements in earlier diagnosis and in treatments mean that five year survival rates have been increasing over time, reaching 87% by 2017 in England.

People who survive breast cancer are at risk of second primary cancer, but until now the exact risk has been unclear. Previously published research suggested that women and men who survive breast cancer are at a 24 and 27% greater risk of a non-breast second primary cancer than the wider population respectively. There have been also suggestions that second primary cancer risks differ by the age at breast cancer diagnosis.

To provide more accurate estimates, a team led by researchers at the University of Cambridge analysed data from over 580,000 female and over 3,500 male breast cancer survivors diagnosed between 1995 and 2019 using the National Cancer Registration Dataset. The results of their analysis are published today in Lancet Regional Health – Europe.

First author Isaac Allen from the Department of Public Health and Primary Care at the University of Cambridge said: “It’s important for us to understand to what extent having one type of cancer puts you at risk of a second cancer at a different site. The female and male breast cancer survivors whose data we studied were at increased risk of a number of second cancers. Knowing this can help inform conversations with their consultants to look out for signs of potential new cancers.”

The researchers found significantly increased risks of cancer in the contralateral (that is, opposite) breast and non-breast second primary cancers for both genders compared to the wider population. The greatest increases in risks were for second cancer of the contralateral breast, and for endometrium and prostate cancer in females and males, respectively.

Females who survived breast cancer were at double the risk of contralateral breast cancer compared to the general population and at 87% greater risk of endometrial cancer, 58% greater risk of myeloid leukaemia and 25% greater risk of ovarian cancer.

Age of diagnosis was important, too – females diagnosed with breast cancer under the age of 50 were 86% more likely to develop a second primary cancer compared to the general population of the same age, whereas women diagnosed after age 50 were at a 17% increased risk. One potential explanation is that a larger number of younger breast cancer survivors carry genetic mutations that increase risk for multiple cancers. For example, women with germline BRCA1 and BRCA2 mutations are at increased risk of contralateral breast cancer, ovarian and pancreatic cancer.

Females from the most socioeconomically deprived backgrounds were at 46% greater risk of a second primary cancer compared to the general population, whereas those from the least deprived backgrounds were at 16% greater risk. These differences were primarily driven by non-breast cancer risks, particularly for lung, kidney, head and neck, bladder, oesophageal and stomach cancers. This may be because smoking, obesity, and alcohol consumption – established risk factors for these cancers – are more common among more deprived groups.

Allen, a PhD student at Clare Hall College, added: “This is further evidence of the health inequalities that people from more deprived backgrounds experience. We need to fully understand why they are at greater risk of second cancers so that we can intervene and reduce this risk.”

Male breast cancer survivors were 55 times more likely than the general male population to develop contralateral breast cancer – though cases were still very rare. They were 58% more likely to develop prostate cancer.

Professor Antonis Antoniou from the Department of Public Health and Primary Care at the University of Cambridge, the study’s senior author, said: “This is the largest study to date to look at the risk in breast cancer survivors of developing a second cancer. We were able to carry this out and calculate more accurate estimates because of the outstanding data sets available to researchers through the NHS.”

The research was funded by Cancer Research UK with support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference

Allen, I, et al. Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study. Lancet Regional Health – Europe; 25 April 2024: DOI: 10.1016/j.lanepe.2024.100903

Treating newly-diagnosed Crohn’s patients with advanced therapy leads to dramatic improvements in outcomes

A large-scale clinical trial of treatment strategies for Crohn’s disease has shown that offering early advanced therapy to all patients straight after diagnosis can drastically improve outcomes, including by reducing the number of people requiring urgent abdominal surgery for treatment of their disease by ten-fold.

The PROFILE trial, led by researchers at the University of Cambridge, involved 386 patients with newly-diagnosed active Crohn’s disease. Recruiting from 40 hospitals across the UK, and supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre and NIHR Clinical Research Network, it sought to test whether a biomarker – a genetic signature – could predict which patients were at greatest risk of relapses of their condition, and to test two different approaches to treating the disease.

Crohn’s disease is a life-long condition characterised by inflammation of the digestive tract. It affects around one in 350 people in the UK. Even at its mildest, it can cause symptoms that have a major impact on quality of life including: stomach pain, diarrhoea, weight loss and fatigue. Typically patients experience ‘flares’ of inflammation, where their condition worsens for a time, producing more symptoms and progressive bowel damage. As many as one in 10 patients will require urgent abdominal surgery to treat their condition within their first year of diagnosis.

The findings of the PROFILE trial, sponsored by Cambridge University Hospitals (CUH) NHS Foundation Trust and the University of Cambridge, are published today (22 February) in The Lancet Gastroenterology and Hepatology. While the biomarker did not prove useful in selecting treatments for individual patients, a ‘top-down’ treatment strategy involving use of the drug infliximab straight after diagnosis, showed dramatic results.

Infliximab works by blocking a protein found in the body’s immune system, TNF (tumour necrosis factor)-alpha, which plays an important role in inflammation. The drug is administered through regular intravenous infusions directly into the bloodstream or injections under the skin. However, due to historical concerns about cost and side-effects – including an increased risk of infection related to immunosuppression – it is currently only offered when patients experience regular flare-ups that do not respond to less potent treatments.

In the PROFILE trial, patients were assigned at random to one of two treatment groups. Each group was given a different treatment strategy and patients were followed up over the course of a year.

The first group was treated using an ‘accelerated step-up’ approach, which is the conventional treatment strategy used in the UK and across most countries around the world. In this group, patients only started on infliximab if their disease was progressing and not responding to other simpler treatments.

The second group, however, was treated using ‘top-down’ therapy – that is, they were provided with infliximab as soon as possible after their diagnosis, regardless of the severity of their symptoms.

The results were dramatic: 80% of people receiving the top-down therapy had both symptoms and inflammatory markers controlled throughout the course of the entire year compared to only 15% of people receiving the accelerated step-up therapy.

Two-thirds (67%) of patients in the ‘top-down’ group had no ulcers seen on their endoscopy camera test at the end of the trial – something known as endoscopic remission. Endoscopic remission is considered very important as this has been consistently associated with decreased risk of later complications in Crohn’s disease. Most previous clinical trials of therapies have been considered highly successful based on getting 20 to 30% of patients into endoscopic remission.

As well as these findings, patients in the top-down arm also had higher quality of life scores, less use of steroid medication and lower number of hospitalisations.

Strikingly, while around one in 20 patients (5%) in the conventional treatment arm of the trial required urgent abdominal surgery for their Crohn’s disease, only one in 193 (0.5%) receiving the ‘top-down’ therapy required such surgery.

Dr Nuru Noor from the Department of Medicine at the University of Cambridge, one of the study’s lead researchers and first author of the trial, said: “Historically, treatment with an advanced therapy like infliximab within two years of diagnosis has been considered ‘early’ and an ‘accelerated step-up’ approach therefore ‘good enough’. But our findings redefine what should be considered early treatment.

“As soon as a patient is diagnosed with Crohn’s disease, the clock is ticking – and has likely been ticking for some time – in terms of damage happening to the bowel, so there’s a need to start on an advanced therapy such as infliximab as soon as possible. We’ve shown that by treating earlier, we can achieve better outcomes for patients than have previously been reported.”

In fact, say the researchers, the improvements seen among the trial patients receiving ‘top-down’ therapy might be even more stark compared to usual clinical care. Few patients with Crohn’s disease in standard clinical care receive the rapid, ‘accelerated step-up’ approach provided by the trial protocol, and so the benefits of implementing a ‘top-down’ approach in standard clinical care might be even more pronounced.

Crucially, the team found no difference in risk of serious infection between treatment strategies, suggesting that infliximab straight after diagnosis was well tolerated, contrary to previous concerns about its safety. In addition, the cost of the drug, which is now an off-patent, generic and ‘biosimilar’ medicine, has fallen considerably from around £15,000 to around £3,000 per patient per year.

Chief Investigator of the PROFILE trial Professor Miles Parkes, Director of the NIHR Cambridge Biomedical Research Centre, said:  “Up until now, the view has been ‘Why would you use a more expensive treatment strategy and potentially over-treat people if there’s a chance they might do fine anyway?’

“As we’ve shown, and as previous studies have demonstrated, there’s actually a pretty high risk that an individual with Crohn’s disease will experience disease flares and complications even in the first year after diagnosis.

“We now know we can prevent the majority of adverse outcomes, including need for urgent surgery, by providing a treatment strategy that is safe and becoming increasingly affordable. If you take a holistic view of safety, including the need for hospitalisations and urgent surgery, then the safest thing from a patient point of view is to offer ‘top-down’ therapy straight after diagnosis rather than having to wait and use ‘step-up’ treatment.”

The PROFILE team are now actively working on an analysis of the health economics to see whether the benefits of the therapy outweigh its cost.

Professor Parkes added: “It’s not just those five per cent of people requiring surgery that we need to think about. In the ‘step-up’ arm lots of people experienced disease flares without necessarily needing surgery. And every time somebody flares, they require several consultations with specialist doctors and nurses, clinical investigations such as scans and colonoscopies, time off work, time out of education and so on – all leading to major impacts on quality of life for individuals.”

While there are other anti-TNF drugs, such as adalimumab, that work in a similar manner to infliximab and are significantly cheaper, more research is required to understand if it would be as clinically effective.

Ruth Wakeman, Director of Services, Advocacy & Evidence at Crohn’s & Colitis UK said: “Crohn’s Disease affects over 200,000 people in the UK and we know that many of them have symptoms for a long time before they are diagnosed. But diagnosis is not the end of their journey, and the trial and error involved in finding the right treatment can be challenging and distressing.

“This study shows what a dramatic difference early treatment with advanced therapy can make to newly-diagnosed patients. People with Crohn’s don’t want to be stuck in hospital or having surgery, they want to be out in the world, living their lives. Anything that speeds up the path to remission can only be a good thing.”

The research was funded by Wellcome and PredictImmune Ltd and supported by the NIHR Cambridge Biomedical Research Centre.

“If the drug had been offered in the first place, things could have been very different.”

Toby Moore, 28, was just ten years old when it became clear there was something wrong.

“I was at primary school at the time and was getting lots of abdominal pain, lots of going to the toilet and vomiting, low energy levels – I was effectively unable to consume any food or drink without some kind of problem. It was just terrible.”

He visited the GP repeatedly over six months, where among other things he was told it was due to the stress of Year Six exams. He says that for his mother and father, it was probably the most challenging time of their lives as parents.

“I was eventually referred to a paediatric gastroenterologist specialist who within 30 seconds of looking at me said, ‘Right. I think you have Crohn’s disease. I’d like to do these tests,’ and off we went.”

The specialist was correct. He put Toby on an ‘elemental diet’ to manage his condition, which meant that for six weeks he could eat no food or drinks (other than water), only prescription shakes aimed at allowing his digestive system to heal. Toby then had to reintroduce different foods into his diet to see if they could identify what triggered his condition.

Not long afterwards, he had a ‘flare up’, with his symptoms worsening significantly. His local Peterborough hospital was unable to help and so he was referred to the Royal Free Hospital in London. There, his parents had to make the difficult decision of whether he should receive abdominal surgery or go onto biologic medication. They chose the latter, and Toby was put on infliximab.

“If you asked my parents now, they’d call it a light switch drug. I was infused with it on a Thursday and by the Sunday I was a different person. I was eating, drinking, my symptoms had stopped. It was unbelievable. Arguably, if that had been offered in the first place instead of the lighter approach, things could have been very different.”

Toby was on infliximab for several years, but was taken off the drug in late secondary school when he became unwell – “not in a Crohn’s disease way, something else was going on”. He was taken into hospital, where the doctors immediately stopped the treatment, concerned it was a trigger.

Toby was transferred to Addenbrooke’s Hospital, where Dr Miles Parkes took over his treatment. It turned out that Toby also had large vessel vasculitis, another autoimmune condition. Whereas Crohn’s affects your digestive system, this affects blood vessels. It causes the aorta, the main blood vessel in your body, to become narrowed, which causes symptoms including weight loss, unexplained lower back pain and fatigue.

Since then, Toby has been on a number of different biologic treatments, each working for a while before their effects wear off, he experiences another flare up, and is prescribed a different drug. Were it not for the drugs, he says his life would be very different.

“It can be quite debilitating, especially when it’s flaring up, as I’m sure you can imagine, when you have minimal control over certain bodily functions. It’s not the most pleasant.”

His current medication, upadacitinib, involves taking a daily pill. It has helped him manage his condition – flare ups aside – allowing him to live a relatively normal life, hold down a steady job as a chef in a local hospice , close to where he lives, and start a family. But he still has to be very careful.

“Where possible I try to avoid stressful situations that life throws at you. When you live at your mum and dad’s life’s a bit more simple, you’ve got a few less responsibilities, so stress is slightly less, but when you go out into the big wide world – and I’ve got a two-and-a-half year old daughter now – that obviously adds a new dynamic to your life!”

Toby has nothing but praise for the NHS. “They’ve been just phenomenal. Miles is very good at nipping things in the bud straight away. He always actions things, he doesn’t just say, ‘Well, we’ll see how you are in a month’. So it never gets too out of control. My opinion of the NHS is really, really high. They’ve been a lifeline for me.”

Paper Reference

Noor NM, Lee JC, Bond S, et al. PROFILE: a multi-centre, randomised, open-label, biomarker-stratified clinical trial of treatment strategies for patients with newly-diagnosed Crohn’s disease. Lancet Gastroenterol Hepatol; 23 Feb 2024; DOI: 10.1016/S2468-1253(24)00034-7

Study estimates number of patients for potential new Alzheimer’s disease treatments

Clinical researchers at Cambridgeshire and Peterborough NHS Foundation Trust and South London and Maudsley NHS Foundation Trust have collaborated to model how many patients might receive new treatments for Alzheimer’s disease currently under review.

Using data on eligible patients from both Trusts and scaling up, the team estimate that a maximum of 30,000 people using dementia services around the country would be suitable for these potential treatments and that NHS providers could provide them on a small scale if approved.

This partnership study was supported by the National Institute for Health and Care Research (NIHR) Cambridge and Maudsley Biomedical Research Centres. Their paper has been shared with research and clinical communities in The British Journal of Psychiatry First View while the drugs are being reviewed for regulatory approval in the UK.

Lead author and CPFT Academic Clinical Fellow Dr Axel Laurell said: “‘Last year the first drugs which can slow down the progression of Alzheimer’s disease by targeting brain amyloid were identified as lecanemab and donanemab. This year they are being considered for approval to use in the UK. We wanted to answer a crucial question to help the NHS plan and prepare, by predicting the largest number of people that might receive these drugs if approved based on eligibility criteria from the clinical trials.”

The study team used anonymised research patient databases from Cambridgeshire and Peterborough and South London and Maudsley NHS Foundation Trusts and examined the records of 82,386 people referred to their services. Applying the eligibility criteria to receive these new types of drugs (monoclonal antibodies) for Alzheimer’s, such as diagnosis, stage of disease, other health conditions, brain imaging data and cognitive test results, they predict that 906 people every year could receive these treatments in their services. This model scales up to indicate around 30,000 people using dementia services nationally might use them. 

Dr Ben Underwood, honorary consultant psychiatrist, Research and Development Director at CPFT and study lead said: “Our work, based on real NHS data, suggests that some of the drugs currently being appraised would only be appropriate for a minority of the people we see in clinic. This gives some idea of the potential scale of the challenge of delivering these new treatments in the NHS if they were approved for use. It is important that we continue to research alternatives that can benefit the majority of people living with Alzheimer’s disease. At CPFT, we work to test and bring the latest proven treatments to our patients as a research active Trust, when their safety and clinical efficacy has been assessed and approved for the NHS.”

Dr Ash Venkataraman, NIHR Academic Clinical Lecturer at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King’s College London, Speciality Registrar in Old Age Psychiatry at South London and Maudsley NHS Foundation Trust and joint lead author said: “There is understandably a lot of anticipation around the potential of these new Alzheimer’s drugs, but they are both expensive and resource intensive as they require regular infusions and brain scans to check suitability and monitor side effects. As such, it is important to have an accurate estimate of how many people may be suitable for these medications to inform service provision. Our study is the first to do this at a detailed level using diverse patient data across two NHS Trusts.”

The NHS is a world leader in rolling out innovative treatments, including personalised cancer and life-saving gene therapies, and has established a dedicated programme team to prepare the NHS for the potential arrival of new Alzheimer’s treatments. They must first be approved by the Medicines and Healthcare products Regulatory Agency (MHRA) and meet National Institute for Health and Care Excellence (NICE) standards for patient safety, clinical and cost effectiveness.

NIHR’s BRCs are collaborations between world-leading universities and NHS organisations that bring together academics and clinicians to translate lab-based scientific breakthroughs into potential new treatments, diagnostics and medical technologies.

Cambridge launches clinical trial to test new drug for a rare lung condition

People with pulmonary sarcoidosis are being invited to take part in an international clinical trial at Cambridge University Hospitals.

The RESOLVE-Lung study, supported by the NIHR Cambridge BRC, is evaluating the safety and effectiveness of a new drug, namilumab, in the treatment of pulmonary sarcoidosis.

Sarcoidosis is a rare inflammatory disease which causes granulomas, tiny clumps of immune cells, to form in any organ or tissue. When it occurs in the lungs it is known as pulmonary sarcoidosis.

Although it most commonly affects the lungs, it can also affect the skin, eyes, joints, nervous system, heart and other parts of the body.

The main symptoms of pulmonary sarcoidosis are shortness of breath and a persistent dry cough, and some people experience pain and discomfort in their chest.

Namilumab is a targeted drug designed to block a molecule which promotes inflammation, thought to be involved in granuloma formation and maintenance. Namilumab has not yet been approved by any health authority for any disease or condition.

Participants in the RESOLVE-Lung study will initially receive monthly injections of namilumab or a placebo (a substance with no therapeutic effect) for approximately six months.

After the initial treatment period, all participants will have the option to receive namilumab for another six months, regardless of whether they initially received namilumab or a placebo.

Up to 100 participants will be enrolled at study sites in the United Kingdom, Europe and the United States.

Dr Akhilesh Jha and Dr Theresia Mikolasch, Co-Principal Investigators of the RESOLVE-Lung study at CUH, said: “Sarcoidosis is a disease that can cause inflammation and scarring of the lungs and is often treated with oral steroids, which are known to have significant side effects.

“The RESOLVE-Lung trial aims to investigate a new treatment for sarcoidosis, which will target inflammation more precisely, and if successful, will provide an alternative option to steroids.

“We are grateful if people with sarcoidosis and clinicians looking after them would consider participating in the study.”

Dr Helen Macdonald, Chief Operating Officer at the NIHR Clinical Research Network East of England, said: “It’s only through research that we can find new treatments for managing long-term conditions such as sarcoidosis. We are hugely grateful to people in the East of England who participate in research, including patients, staff and supporters alike.”

To find out more about the RESOLVE-Lung study, please visit www.sarcoidosistrial.com/en-uk.

Cambridge-led study discovers cause of pregnancy sickness – and potential treatment

A Cambridge-led study supported by the NIHR Cambridge BRC has shown why many women experience nausea and vomiting during pregnancy – and why some women, including the Duchess of Cambridge, become so sick they need to be admitted to hospital.

The culprit is a hormone produced by the fetus – a protein known as GDF15. But how sick the mother feels depends on a combination of how much of the hormone is produced by the fetus and how much exposure the mother had to this hormone before becoming pregnant.

The discovery, published today (13 December 2023) in Nature, points to a potential way to prevent pregnancy sickness by exposing mothers to GDF15 ahead of pregnancy to build up their resilience.

As many as seven in ten pregnancies are affected by nausea and vomiting. In some women – thought to be between one and three in 100 pregnancies – it can be severe, even threatening the life of the fetus and the mother and requiring intravenous fluid replacement to prevent dangerous levels of dehydration. So-called hyperemesis gravidarum is the commonest cause of admission to hospital of women in the first three months of pregnancy.

Although some therapies exist to treat pregnancy sickness and are at least partially effective, widespread ignorance of the disorder compounded by fear of using medication in pregnancy mean that many women with this condition are inadequately treated.

Until recently, the cause of pregnancy sickness was entirely unknown. Recently, some evidence, from biochemical and genetic studies has suggested that it might relate to the production by the placenta of the hormone GDF15, which acts on the mother’s brain to cause her to feel nauseous and vomit.

Now, an international study, involving scientists at the University of Cambridge and researchers in Scotland, the USA and Sri Lanka, has made a major advance in understanding the role of GDF15 in pregnancy sickness, including hyperemesis gravidarum.

The team studied data from women recruited to a number of studies, including at the Rosie Maternity Hospital, part of Cambridge University Hospitals NHS Foundation Trust and Peterborough City Hospital, North West Anglia NHS Foundation Trust. They used a combination of approaches including human genetics, new ways of measuring hormones in pregnant women’s blood.

The researchers showed that the degree of nausea and vomiting that a woman experiences in pregnancy is directly related to both the amount of GDF15 made by the fetal part of placenta and sent into her bloodstream, and how sensitive she is to the nauseating effect of this hormone.

GDF15 is made at low levels in all tissues outside of pregnancy. How sensitive the mother is to the hormone during pregnancy is influenced by how much of it she was exposed to prior to pregnancy – women with normally low levels of GDF15 in blood have a higher risk of developing severe nausea and vomiting in pregnancy.

The team found that a rare genetic variant that puts women at a much greater risk of hyperemesis gravidarum was associated with lower levels of the hormone in the blood and tissues outside of pregnancy. Similarly, women with the inherited blood disorder beta thalassemia, which causes them to have naturally very high levels of GDF15 prior to pregnancy, experience little or no nausea or vomiting.

“We now know why: the baby growing in the womb is producing a hormone at levels the mother is not used to. The more sensitive she is to this hormone, the sicker she will become. Knowing this gives us a clue as to how we might prevent this from happening. It also makes us more confident that preventing GDF15 from accessing its highly specific receptor in the mother’s brain will ultimately form the basis for an effective and safe way of treating this disorder.”

Previous studies of mice exposed to acute, high levels of GDF15 showed signs of loss of appetite, suggesting that they were experiencing nausea, but mice treated with a long-acting form of GDF15 did not show similar behaviour when exposed to acute levels of the hormone. The researchers believe that building up woman’s tolerance to the hormone prior to pregnancy could hold the key to preventing sickness.

Co-author Dr Marlena Fejzo from the Department of Population and Public Health Sciences at the University of Southern California whose team had previously identified the genetic association between GDF15 and hyperemesis gravidarum, has first-hand experience with the condition. “When I was pregnant, I became so ill that I could barely move without being sick. When I tried to find out why, I realized how little was known about my condition, despite pregnancy nausea being very common.

“Hopefully, now that we understand the cause of hyperemesis gravidarum, we’re a step closer to developing effective treatments to stop other mothers going through what I and many other women have experienced.”

The work involved collaboration between scientists at the University of Cambridge, University of Southern California, University of Edinburgh, University of Glasgow and Kelaniya University, Colombo, Sri Lanka. The principal UK funders of the study were the Medical Research Council and Wellcome, with support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Professor Sir Stephen O’Rahilly added: “The support of the NIHR Cambridge Biomedical Research Centre has been critical for the success of this study. The BRC has provided crucial support to our Peptidomics lab to help with our analysis and access to resources like the BRC supported Clinical Biochemistry Assay lab has been essential to deliver this significant breakthrough in understanding hyperemesis gravidarum.

“The BRC provides us with an opportunity to collaborate with expertise from University of Cambridge, Cambridge University Hospitals and other research themes like Professor Gordon Smith, whose samples from his POPS study was vital in our discovery. Without the necessary infrastructure and resources the BRC provides, this study would not have been made possible.”

Professor Miles Parkes, NIHR Cambridge BRC director said: “Its great to see this great breakthrough coming out of the O’Rahilly group. It represents a major step towards better treatment of hyperemesis gravidarum – the most severe and dangerous form of nausea and vomiting in pregnancy that often leads to mums spending long periods in hospital. This work has been supported at each step by the research infrastructure of the NIHR Cambridge Biomedical Research Centre. It emphasises the importance of this NHS-funded infrastructure in delivering major biomedical discoveries of potentially transformational significance with regards to improved health of patients in Cambridge and around the world”

“I was told: ‘Oh, for God’s sake, you’ve just got morning sickness. Pull yourself together.’”

Charlotte Howden considered herself to be in good health prior to getting pregnant in her early thirties. Her pregnancy was proceeding as normal until around week six or seven, when she began feel nauseous. Even then, she didn’t see any reason to be concerned.

“It’s just what we’ve been told to expect in early pregnancy,” she says.

Around a week after the onset of nausea, Charlotte’s condition got worse. Much worse. She found herself being sick as often as 30 times a day, unable to keep food down.

“Every time I tried to eat something, which is obviously what I wanted to do, not only because I felt hungry, but because I was pregnant, that would then instantly make me sick.”

Worse still, she could not keep any fluids down – not even water. Her condition – which she now knows to be hyperemesis gravidarum (HG) – became so bad that even to swallow saliva would make her sick. And a cruel irony is that a common symptom of HG is excessive saliva production.

When Charlotte finally accepted that there was something wrong, that this was not normal pregnancy sickness, she turned to her GP.

“They just said ‘There’s nothing we can do for you. Have you tried ginger? Try and limit your daily activities to best get through this. Try eating a little and often.’”

Returning to the GP, she was offered a urine test for levels of ketones, a chemical produced by the liver (high levels can indicate a serious problem) – the only way, it seemed, that she would be diagnosed with dehydration and referred for treatment. And given that she had not been taking any fluids, this made taking the test incredibly difficult.

“For some reason, it’s only women with HG who are asked to give a sample, when other conditions it is obvious from the way someone looks,” she says.

Charlotte was not referred, but instead her GP prescribed her the first line medication for HG. This did little to help.

“It just makes you comatose, so you sleep the whole day. But I had a full time job, I had responsibilities, financial and otherwise. Sleeping 20 hours a day is not an effective way to live!”

A second ketone test showed that something was obviously wrong. She was told to get to the hospital immediately.

Charlotte was admitted to the early pregnancy ward, which she describes as a traumatic experience.

“You’re with women who are losing their pregnancies, and you’re very much still pregnant. There’s a kind of dismissive behaviour around you of, ‘Oh, for God’s sake, you’ve just got morning sickness. That woman over there has just had a miscarriage. Pull yourself together.’”

After being rehydrated, she was discharged, only to become very sick again and be re-admitted. This cycle repeated, taking its toll.

“Mentally you end up thinking to yourself there is no point in going back to hospital. The definition of insanity is doing the same thing over and over again. You feel completely broken.”

Eventually, she had had enough.

“When I went in again for my third time, I begged [the consultant] to help me because I was very close to making the decision to terminate. She said ‘Look, just give me 24 hours.’”

This time, the consultant gave her medication that finally made her “feel incredible” for 12 hours. Discharged, she would need to get a repeat prescription from her GP – something they were unwilling to do.

“There was a complete disconnect between my GP and the consultant,” she says. Fortunately, Charlotte, rehydrated and re-energised, was ready to fight. She managed to get through to the consultant, who was astounded to hear she was being refused the medication.

“She got on the phone to the GP and I won’t repeat the language she used, but she was very stern, quite rightly, because what’s the point of treating someone in hospital and then just sending them home to come back in a couple of days’ time?”

It took Charlotte until around week 16 of her pregnancy before she was finally on the right treatment to overcome her sickness. She continued taking the medication until around week 37 as she was “petrified to stop taking it”.

In 2016, Charlotte gave birth to a healthy son, Henry. She is determined that no woman should have to go through what she did. In 2020, she presented the world’s first documentary on HG, Sick – The Battle Against HG.

Charlotte became involved with the charity Pregnancy Sickness Support, joining an army of around 600 volunteers who offer peer support and man telephone helplines. She is now its Chief Executive and uses her position to raise awareness of the condition among women and healthcare professionals, including pushing for HG to be taught on all midwifery courses.

Charlotte is hopeful that this new study will lead to a way of treating – and even preventing – HG. She is grateful to Professor O’Rahilly and Dr Fejzo for their work – and in particularly, for taking the condition seriously.

“When you are suffering from a condition and no one can tell you why, you start to think, oh, is it me? Is it something I’ve done?” she says. “I’m so grateful for the dedication of the researchers, because this isn’t a condition that really ever made the headlines until the now Princess of Wales suffered with it. It wasn’t an area of research that people were really interested in. It was just morning sickness – why should we care?”

Reference

Fejzo, M et al. Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy. Nature; 13 Dec 2023; DOI: 10.1038/s41586-023-06921-9

Research nurse’s poster on complex cancer study wins first prize at public event

“It’s all about collaboration. Collaboration with people across the Cambridge Biomedical Campus was key to getting this study off the ground,” was the first thing Jason Domingo, senior clinical research charge nurse from the NIHR Cambridge Clinical Research Facility (CRF) said on winning the poster competition at the NIHR Cambridge BRC open evening which took place in November.

His poster highlighted the crucial elements of working with multiple hospital teams to set up a complex cancer trial and to try and improve the patient’s research journey.

The poster was one of 14 on display and was voted the winner by members of the public and healthcare professionals.

“This particular cancer trial involved a multi-team effort,” Jason emphasised. “It was a first-in-human trial to be hosted at the NIHR Cambridge CRF and we were only one of nine sites in the world. This treatment-trial was looking at radiation therapy to see if it could help patients with advanced tumours with overexpression of Gastrin-Releasing Peptide Receptor (GRPR), a receptor normally present on some body cells.

“The trial involved giving a radiation infusion to patients, they would then have regular bloods taken and scans to monitor the effects of the treatment. As well as providing radiation treatment, we were dealing with lots of new equipment like a dosimeter and Geiger-Muller contamination monitor that detects and measures radiation that you have been exposed to.

“This meant we had to set up our clinical rooms in a certain way and learn how to monitor radiation levels safely. All the staff had specific radiation safety training and learned how to use the right protective clothing and decontamination procedures.

“In order to set the study up in the CRF, we had to work closely with the hospital’s Cambridge Cancer Trials Centre, Nuclear Medicine, Estates and Facilities, Clinical Trials Pharmacy and Infection Control teams as well as the researchers, it was a team effort. Nuclear Medicine staff provided us with safety training to make sure we could run the study and we also completed risk assessments on members of staff to make sure they were safe to work on the trial.  

“Being a patient-centric trial we then wanted to make sure the patients had a full understanding of what was involved and we wanted to them to have a good experience. The trial involved them staying overnight multiple times and some of the patients participating were coming from outside Cambridge.  

“We then decided to invite eligible patients to come and look around the facility, to see their private en-suite room, meet the staff and have the opportunity to ask any questions.  

“When they joined the trial it went really well. The radiation levels we were dealing with were low and safe for us to work, we were very well monitored by the hospital’s nuclear medicine team. The estates team ensured that trial’s urine samples will not contaminate others’, and infection control team made sure we had the right protective clothing and minimised any risks.

“The patients were comfortable and closely monitored, and they gave some really nice feedback at the end of their visits. They liked the facilities, knowing the hospital was nearby and enjoyed the calming atmosphere of the CRF.

“We knew this trial was going to be a new challenge but we had the support of so many hospital teams. We couldn’t have done it without them and part of this award goes to them as well.”

Caroline McMahon, patient and public involvement coordinator at the NIHR Cambridge CRF, who worked on the poster with Jason said: “This poster is a prime example of why CRFs exist. We provide a dedicated space with experienced research nurses, facilities, expertise, resources and support staff to run trials like this, and without the help of other teams this study just wouldn’t have happened. Now the staff have this experience it means we can run more of these kind of trials in the future. Cambridge is an amazing place to do research, we’re fortunate that our CRF is based in the heart of the Cambridge Biomedical Campus and can work collaboratively with many different specialities.”

Jason added: “But it’s not just having the facilities and space, it’s the patients who really make a difference. Without our participants we couldn’t do research. I want to thank them all, any contribution whether it’s giving feedback or taking part in a trial makes a huge difference and it’s really valuable to us. Truly, today’s research has the potential to become tomorrow’s care and practice.”

Newborn babies at risk from bacteria commonly carried by mothers

One in 200 newborns is admitted to a neonatal unit with sepsis caused by a bacteria commonly carried by their mothers – much greater than the previous estimate, say Cambridge researchers. The team has developed an ultra-sensitive test capable of better detecting the bacteria, as it is missed in the vast majority of cases.

Streptococcus agalactiae (known as Group B Streptococcus, or GBS) is present in the genital tract in around one in five women. Previous research by the team at the University of Cambridge and Rosie Hospital, Cambridge, identified GBS in the placenta of around 5% of women prior to the onset of labour. Although it can be treated with antibiotics, unless screened, women will not know they are carriers.

GBS can cause sepsis, a life-threatening reaction to an infection, in the newborn. Worldwide, GBS accounts for around 50,000 stillbirths and as many as 100,000 infant deaths per year.

In a study published in Nature Microbiology, the team looked at the link between the presence of GBS in the placenta and the risk of admission of the baby to a neonatal unit. The researchers re-analysed data available from their previous study of 436 infants born at term, confirming their findings in a second cohort of 925 pregnancies.

From their analysis, the researchers estimate that placental GBS was associated with a two- to three-fold increased risk of neonatal unit admission, with one in 200 babies admitted with sepsis associated with GBS – almost 10 times the previous estimate. The clinical assessment of these babies using the current diagnostic testing identified GBS in less than one in five of these cases.

In the USA, all pregnant women are routinely screened for GBS and treated with antibiotics if found to be positive. In the UK, women who test positive for GBS are also treated with antibiotics. However, only a minority of pregnant women are tested for GBS, as the approach in the UK is to obtain samples only from women experiencing complications, or with other risk factors.

There are a number of reasons why women in the UK are not screened, including the fact that detecting GBS in the mother is not always straightforward and only a small minority of babies exposed to the bacteria were thought to become ill. A randomised controlled trial of screening for GBS for treatment with antibiotics is currently underway in the UK.

Dr Francesca Gaccioli from the Department of Obstetrics & Gynaecology at the University of Cambridge said: “In the UK, we’ve traditionally not screened mothers for GBS, but our findings – that significantly more newborns are admitted to the neonatal unit as a result of GBS-related sepsis than was previously thought – profoundly changes the risk/benefit balance of universal screening.”

To improve detection, the researchers have developed an ultrasensitive PCR test, which amplifies tiny amounts of DNA or RNA from a suspected sample to check for the presence of GBS. They have filed a patent with Cambridge Enterprise, the University of Cambridge’s technology transfer arm, for this test.

Professor Gordon Smith, Head of Obstetrics & Gynaecology at the University of Cambridge, said: “Using this new test, we now realise that the clinically detected cases of GBS may represent the tip of the iceberg of complications arising from this infection. We hope that the ultra-sensitive test developed by our team might lead to viable point-of-care testing to inform immediate neonatal care.”

When the researchers analysed serum from the babies’ umbilical cords, they found that over a third showed greatly increased levels of several cytokines – protein messengers release by the immune system. This suggests that a so-called ‘cytokine storm’ – an extreme immune response that causes collateral damage to the host – was behind the increased risk of disease.

Professor Gordon Smith added: “The study required meticulous collection of data and biological samples and involved molecular analysis of more than 1,300 placental samples. These were collected as part of the Pregnancy Outcome Prediction study, funded by the Cambridge NIHR Biomedical Research Centre, which generated a unique and valuable resource to address this and other important questions about what determines healthy and a complex pregnancy.”

The research was funded by the Medical Research Council and supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

Reference

Gaccioli, F, Stephens, K & Sovio, U et al. Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and fetal pro-inflammatory cytokines in term infants. Nature Microbiology; 29 Nov 2023; DOI: 10.1038/s41564-023-01528-2

Patient and Public Involvement Network – next meeting 24 January

Do you work at the Cambridge Biomedical Campus in a Patient and Public Involvement role or are you working to involve the public in your practice or research? 

Would you like to meet others working in similar roles?

For the past 5 years, NIHR Cambridge Biomedical Research Centre has hosted a network for people interested in PPI across the Biomedical Campus. The network provides an opportunity for colleagues across the campus to come together, share ideas and challenges and explore ways to support each other with involving the public in research.

If you work at the Cambridge Biomedical Campus you can attend the next meeting on 24 January, 14:00-15:00, please contact CUH.PPI@nhs.net to register and for further details.

Prestigious NIHR Research Professorship awarded to Cambridge researcher

Congratulations to co-theme lead for the NIHR Cambridge BRC Data Science and Population Health theme, Professor Angela Wood, who has been awarded an NIHR Research Professorship.

Professor Angela Wood, Professor of Health Data Science, whose research focuses on the use of population health data for the prevention of numerous chronic diseases, is one of six leading researchers in England who has been given this prestigious award.

The NIHR Research Professorships scheme funds and supports research leaders of the future. It aims to strengthen and benefit health, public health and care research leadership.

The researchers will receive five-year awards of up to £2 million as well as a package of extensive support, including three support posts and access to a leadership and development programme.

Professor Wood said: “I’m really delighted and honoured to receive the NIHR Research Professorship Award. My goal is to advance the prevention of multiple chronic diseases by harnessing population-wide health data. I will develop new methods to identify who will benefit the most from specific interventions and when is the best time to start them.” 

Since 2011, 66 people have been successful in gaining the competitive award. Many have gone on to become senior research leaders. This includes Professor Lucy Chappell, Chief Scientific Adviser to the Department of Health and Social Care and CEO of the NIHR.

Professor Waljit Dhillo, Dean of the NIHR Academy and Scientific Director for Research Capacity and Capabilities, said: “I am delighted and honoured to welcome the latest group of outstanding researchers to the NIHR Research Professorship scheme. I look forward to seeing the difference their research will make to the lives of people and communities across the UK.

“The NIHR Research Professorship is one of the most prestigious awards we offer. Their expertise in health and care research will help improve people’s health and wellbeing.”

NIHR Research Professors

The five other researchers to receive a 2023 NIHR research professorship are:

• Professor Samuele Cortese, University of Southampton. Their research topic is: Personalising the pharmacological treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children
• Professor Daniela Ferreira, Professor of Vaccinology, University of Oxford. Their research topic is: Understanding nasal immunity to improve vaccine protection against respiratory infections
• Professor Shonit Punwani, University College London. Their research topic is: Smarter identification and management of Early prostate cancer: improving Lives and outcomEs through Clinical Translation of novel magnetic resonance imaging (SELeCT)
• Professor Matthew Ridd, University of Bristol. Their research topic is: Transforming Outcomes for Paediatric allergy in primary care (TOPIC)
• Professor Reecha Sofat, University of Liverpool. Their research topic is: CAUsal Inference Methods to Inform MedicineS ReguLation and Guidance: CAUSAL

Cambridge announced as a major collaborator in new paediatric HealthTech Research Centre

NIHR Cambridge BRC researchers will be supporting a new paediatric research centre hosted by Sheffield, which aims to develop new technologies that improve healthcare in children and young people.  

The Children and Young People HealthTech Research Centre (HRC), led by Sheffield Children’s NHS Foundation Trust, was awarded a £3 million grant from the National Institute for Health and Care Research to identify new ways to improve the management of rare and long-term conditions in babies to young adults.

The award will see Cambridge researchers working in collaboration with Sheffield’s HRC and other expertise across the country to support the development of new medical devices, diagnostics and digital technologies.

Cambridge researchers will focus on the Mind-Body Integration (MBI) theme of the HRC, which is inspired by a growing recognition of the need to jointly consider the physical and psychological needs of children.

Researchers will look at how the interactions of the ‘brain-body’ affect children in order to create new therapies that can target both physical and mental health from birth. They will also look at addressing unmet challenges such as:

• Supporting the mental health needs of parents of babies who are admitted to neonatal intensive care, 80% of whom go on to suffer mental illness.
• How to improve mental health outcomes in babies who spent time in neonatal intensive care, who currently experience twice the rate of subsequent psychiatric problems.
• Optimising treatment and care for children with epilepsy, 30-50% of whom have co-occurring psychiatric problems.
• Reducing depression in adolescents with diabetes.
• Responding to the 20% increase in demand for mental health support in under-18s that has occurred since the COVID-19 pandemic.

Professor Paul Dimitri, Clinical Director of Innovation and Technology at Sheffield Children’s NHS Foundation Trust, said: “This is an historic milestone positioning Sheffield at the cutting edge of paediatric research and innovation worldwide. The HRC and NCCHT will pioneer the health technologies of tomorrow, delivering dramatic improvements in NHS care that benefit generations to come. We aim to create a lasting legacy for children’s health.”

New HRC for Cambridge

As part of the announcement from the NIHR, Cambridge has been selected to host another arm of the HRC where they will be leading on new ways to improve the experiences of people affected with brain and spinal injuries.

The new Brain and Spine Injury HRC, based at Cambridge University Hospitals, received nearly £3 million in mid-November. Researchers will be collaborating with other teams across England and will focus on five clinical themes. This new HRC will be led by NIHR Cambridge BRC researcher and neurosurgeon, Professor Peter Hutchinson and academic neurosurgeon, Dr Alexis Joannides.

Dr Joannides said: “The new HRC will enable us to build on the Brain MIC’s achievements and work effectively with inventors, academics, and clinicians within the UK and beyond to identify, evaluate, and implement meaningful solutions to improve the lives of people affected by brain injury.”

Professor Hutchinson added: “This funding from the National Institute for Health and Care Research will make a major contribution to the outcome of patients with brain and spine injury. Engaging patients and the public will help us to identify areas of unmet need and working with industry will facilitate the development of new devices and treatment.”

About HRC

From 1 April 2023 the NIHR will launch 14 new HRCs to work to develop new and improved treatments and enable people to better monitor their health, diagnose

ill health sooner and improve management of conditions including cancer, dementia,

cardiovascular and respiratory disease.

The HRCs will also work with companies to develop and test products to support rehabilitation and help those with social care needs to maintain their independence. They will work closely with carers, patients and users at all stages.

Each HRC will be hosted by an NHS organisation in England, bringing industry, academia and the health and care system together. The HRCs will drive innovation and efficiency, bringing new technologies to those who need them most, support the health and care workforce to reduce workload, and help alleviate pressures on the health and care system.

The HRCs will keep the UK at the forefront of research and the place companies want to come to in order to invest in the development of health technologies.

Full list of HRCs

Cambridge University Hospitals NHS Foundation Trust Brain and spine injury

Guy’s and St Thomas’ NHS Foundation Trust Cardiovascular and respiratory disease

Imperial College Healthcare NHS Trust Diagnostics for cancer, infectious and respiratory diseases, critical care, primary and social care

Leeds Teaching Hospitals NHS Trust Surgical technologies and rehabilitation

Manchester University NHS Foundation Trust Urgent and emergency care

Nottinghamshire Healthcare NHS Foundation Trust Mental health

Nottingham University Hospitals NHS Trust Rehabilitation and assistive technologies

Oxford Health NHS Foundation Trust Community healthcare (cancer, infectious diseases, mental health and technology for care homes)

Royal Devon University Healthcare NHS Foundation Trust Diagnostics, rehabilitation and frailty

Sheffield Children’s NHS Foundation Trust Children and young people’s health

Sheffield Teaching Hospitals NHS Foundation Trust Long-term neurological conditions, diabetes, kidney care, women’s health, rehabilitation, mental health

South London and Maudsley NHS Foundation Trust Dementia and brain health

The Newcastle Upon Tyne Hospitals NHS Foundation Trust Diagnostics for infectious diseases, ageing and multiple long-term conditions and rare diseases

University Hospitals Birmingham NHS Foundation Trust Trauma and emergency care

Find out more on the NIHR website.