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Author: Louise Stanley

Funding renewal allows experimental cancer therapy research to continue in Birmingham

Written by Louise Stanley on . Posted in Cancer outcomes, Experimental medicine.

New and innovative ways to detect and treat cancer being trialled at the University of Birmingham are to receive renewed funding from Cancer Research UK and the NIHR.

The Birmingham Experimental Cancer Medicine Centre (ECMC), jointly funded by Cancer Research UK and the National Institute for Health and Care Research in England, provides world-leading expertise in the development of innovative cancer trials. New funding will enable the Birmingham ECMC to continue to conduct the highest quality trials into experimental treatments for cancer over the next five years.

The centre aims to be an integrated translational hub for cancer research in Birmingham and brings together the University of Birmingham’s global expertise in cancer research and strength in clinical trials to deliver accelerated patient benefit regionally, across the ECMC network and globally.

The centre is part of world-leading cancer research infrastructure in Birmingham alongside the Birmingham Cancer Research Clinical Trials Unit (CRCTU) and the NIHR Biomedical Research Centre. The funding enables the University of Birmingham, working closely together with organisations across the Birmingham Health Partners network, to focus on three themes in experimental cancer medicine: Precision Medicine, Cancer Immunotherapy and Biomarker-driven patient stratification.

Gary Middleton, Professor of Medical Oncology and Centre Director for the Birmingham Experimental Cancer Medicine Centre said:

“Thanks to the funding from Cancer Research UK and the National Institute for Health and Care Research we will be able to continue to design and deliver trials that have the power to make a huge difference to the lives of cancer patients.

“Over the past five years we have already made significant advances in precision medicine for cancer including through the National Lung Matrix trial. With renewed funding we will be able to drive forward the next generation of these studies, offering access to personalised therapies to cancer patients in the West Midlands and across the national ECMC network.”

Case study: Lung Matrix Trial

Executive Director of Research and Innovation at Cancer Research UK, Dr Iain Foulkes, said:

“We are proud to be supporting an expansion of our successful ECMC network, bringing together vast medical and scientific expertise to translate the latest scientific discoveries from the lab into the clinic.

“The ECMC network is delivering the cancer treatments of the future, bringing new hope to people affected by cancer. The trials taking place today will give the next generation the best possible chance of beating cancer.

Chief Executive of the NIHR, Professor Lucy Chappell, said:

“The ECMC Network is a vital strategic investment in the UK’s cancer research community, bringing together top scientists and clinicians to tackle some of the biggest scientific challenges in cancer and improve outcomes for patients.

“Through this route, we enable more people to join trials that could help them. The ECMC Network will give access to brand new experimental treatments for patients, including children and young people, paving the way for these treatments to be used in the clinic one day. This is a crucial part of NIHR’s work, and enables more people to join trials that might help them. We are proud to be partnering with Cancer Research UK and the Little Princess Trust in funding this network.”

Building on success

Birmingham is part of a network of 17 ECMCs across the UK, funded by Cancer Research UK and the NIHR, which deliver clinical trials of promising new treatments. Since 2007, when the network was first established, around 30,000 patients have taken part in 2,100 trials.

The funding will allow new, experimental treatments – including immunotherapies – for a wide variety of cancers to be developed, as well as improve existing treatments.

ECMCs work in conjunction with local NHS facilities to provide access to cutting-edge cancer treatments. Testing these treatments helps to establish new ways of detecting and monitoring the disease and to evaluate how it responds to the treatment.

DETERMINE

The University of Birmingham is part of a newly announced partnership which is running a multi-drug, precision medicine platform trial for adults and children with rare cancers who have run out of other treatment options.

The DETERMINE trial is one of the largest precision medicine platform trials targeting these populations and it will enrol patients who have an identifiable genetic alteration in their cancer that can be targeted by treatments that are already approved for use in other cancer types.

The trial is aiming to recruit patients with rare adult and paediatric cancers, as well as more common cancers with rare genetic alterations that could be targeted by the drugs being studied in the trial.

New device provides early diagnosis for cardiac tamponade

Written by Louise Stanley on . Posted in Early diagnosis and detection.

A new diagnostic device, developed to monitor against post-surgery heart strangulation risk, has been introduced by a company formed by Birmingham cardiothoracic surgeon Hazem Fallouh.

Patients recovering from heart surgery can be at risk from a life-threatening condition – cardiac tamponade – where fluid builds up around the heart, strangling its ability to beat properly.

Fallouh Healthcare is developing the device to monitor cardiac patients after surgery, which is when cardiac tamponade usually strikes – and has received a £500k grant from Innovate UK.

Typically, cardiac tamponade happens late at night when the patient is in intensive care. Blood clots accumulate and compress the heart, reducing its ability to pump blood around the body.

Around 45,000 patients in the UK undergo cardiac surgery each year, and it is usually safe. However cardiac tamponade can come on quickly, and diagnosis is difficult as it can be confused with other causes of heart failure. As high as 3 in 10 of all deaths that immediately follow post-cardiac surgery are thought to be due to cardiac tamponade.

If missed, cardiac tamponade can lead to cardiac arrest which is resistant to CPR and requires immediate opening of the patient’s chest in the uncontrolled environment of the intensive care unit – a procedure that has a mortality rate (30-70%), and poor outcomes for those patients who survive.

Consultant surgeon Mr Fallouh, who has worked in many centres of excellence in the UK, invented the device to provide early diagnosis of tamponade, allowing a planned return to surgery to drain fluid and clots around the heart.

Called PerDeCT (Pericardial Device to monitor Cardiac output and diagnose Tamponade), it is the only device to diagnose cardiac tamponade, and provide cardiac monitoring at no extra cost.

In 2021, Dr Fallouh, who has previously commercialised two award-winning inventions in cardiac surgery, received the prestigious Techno-College Innovation Award at the 35th Annual Meeting of European Society of Cardiothoracic Surgery for PerDeCT, by panels of expert surgeons, cardiologists and medical devices and investment specialists.

The device consists of a probe and a balloon, which is placed in the pericardium (the sac around the heart) during initial surgery, and measures cardiac efficiency (cardiac output) as well as predicting the development of tamponade, by looking at the trend in the relationship between balloon inflation and cardiac efficiency. It can be withdrawn through the skin after the patient is recovered.

The intellectual property in the form of a patent is assigned to Fallouh Healthcare Limited.

Fallouh Healthcare is a startup with a mission to deliver smart solutions to unmet needs in order to deliver safer and more effective cardiothoracic surgery.

The company has now taken up residency in Unit 9, a short-term medical technology incubator funded by University of Birmingham Enterprise, the Greater Birmingham & Solihull Local Enterprise Growth Hub and the West Midlands Combined Authority to provide flexible, low-cost facilities for medical research, proof of concept and prototyping activity.

The delivery of the Innovate UK project is in collaboration with University Hospitals Birmingham NHS Foundation Trust (UHB) and the University of Sheffield. The funding from Innovate UK will allow Fallouh Healthcare to build a prototype and conduct a usability study at UHB’s Queen Elizabeth Hospital site, the Medical Device – Testing and Evaluation Centre (MD-TEC).

New heart attack drug trialled in Birmingham

Written by Louise Stanley on . Posted in Clinical trials.

A new partnership between BHP clinical-academic institutions and Acticor Biotech will see patients with heart attacks treated with glenzocimab, a promising new class of drug, for the first time.

The drug – which has potential to improve the long-term outcomes for heart attack patients – will be trialled in two UK acute care hospitals: the Queen Elizabeth Hospital, Birmingham and the Northern General Hospital, Sheffield.The trial will be run at the University of Birmingham with expert clinicians from the Institute of Cardiovascular Sciences and University Hospitals Birmingham NHS Foundation Trust, bringing together clinical trials expertise from two founding members of BHP.

The randomised, double-blind Phase 2b LIBERATE study will recruit more than 200 patients to test the tolerance and the efficacy of glenzocimab 1000 mg, versus placebo, to reduce heart damage following a myocardial infarction (MI), commonly known as a heart attack. Bringing together experience in running multi-site trials from the Clinical Trials Units and expertise in heart diseases, the team will see whether glenzocimab will reduce the amount of dead heart tissue in patients following an ST-segment elevation myocardial infarction (STEMI), the most serious type of heart attack.

Professor Jon Townend, Consultant Cardiologist at University Hospitals Birmingham, Honorary Professor of Cardiology in the Institute of Cardiovascular Sciences at the University of Birmingham, and Chief Investigator of the trial said: “We look forward to starting this exciting trial of a new drug for heart attacks which are still only too common.

“Although immediate opening of the blocked coronary artery by angioplasty in cases of heart attack is now routine, significant heart damage still occurs. Glenzocimab reduces clot formation and laboratory findings have been impressive.

“There are strong reasons to believe that this new drug may improve outcomes and this randomised blinded trial is the right way to test this theory.”

Dr Mark Thomas, Associate Professor of Cardiology at the University of Birmingham and Honorary Consultant Cardiologist, who designed the trial and led its development, said: “This trial will help us establish whether glenzocimab is a safe and effective drug for preventing the kind of clotting that can lead to serious damage to the heart following a heart attack.

“We’re delighted to work with Acticor Biotech to see whether this new class of drug has the potential to improve the outcomes of our patients with heart attacks. While the immediate care provided for a heart attack is effective for improving patient survival, there is more we can do to prevent long-term damage to the heart.”

Gilles Avenard, Chief Executive Officer and founder of Acticor Biotech said: “Glenzocimab has already delivered very promising results in the treatment of acute ischemic stroke and we hope to confirm its therapeutics potential in another severe indication.

“We are proud of this Phase 2b study launch, which allows glenzocimab development programme extension to myocardial infarction. We would like to congratulate all the teams involved, the University of Birmingham particularly, sponsor of this study.”

Glenzocimab, a humanized monoclonal antibody (mAb) fragment directed against the platelet Glycoprotein VI (GPVI), was developed by Acticor Biotech for the treatment of cardiovascular emergencies, including stroke.

This new drug, currently being trialled for strokes, stops the functioning of platelets that cause abnormal clotting of blood. While platelet function is normally important to stop bleeding, this drug specifically targets only dangerous clotting inside damaged blood vessels called thrombosis that can cause strokes and heart attacks.

The BHP Starter Fellowship – a catch-up with Karl

Written by Louise Stanley on . Posted in Birmingham Health Partners.

Karl Payne

Dr Karl Payne is currently an NIHR funded Academic Clinical Lecturer in Oral & Maxillofacial Surgery and a Surgical Trainee in the West Midlands. He undertook a Birmingham Health Partners Starter Fellowship in 2018 – 2019 and, having shared his thoughts with us soon after completing his fellowship, is back to update us on his progress in the years since.

When we last spoke to you, you’d just completed your BHP Fellowship and had ‘taken a gamble’ to use it as the first year of your PhD. What is your research topic and how are you progressing?

My research topic continues to be focused on a liquid biopsy in head and neck cancer. Specifically using a simple blood test to detect tumour specific markers that can could pick up recurrence or metastasis earlier than conventional methods, and hopefully direct treatment in these groups. I’ve been using a novel platform to capture circulating tumour cells and do multi-plex proteomic analysis. For the first time we can interrogate up to 44 proteins on cancer cells derived from a patients blood, far beyond current standards. We are progressing well. I’ve run my first pilot cohort and we are planning a larger trial also incorporating genomic assessment of circulating tumour DNA. I’m excited, but then I would be, it’s my project!….

Do you feel the fellowship was advantageous to you in your PhD, compared with a traditional route? 

Firstly, it’s always advantageous to be paid! That might sound a bit clichéd, but any salary-funded fellowship buys you the opportunity to spend time doing research outside of clinical training. I think what sets the BHP fellowship apart is the integration within existing clinical academic pathways, while also recognising the need to support those aspiring academics who haven’t been able to get an academic post in their training but need that first bit of help to get some pilot data.

It depends what route you are taking and which specialty, but certainly in surgery it was invaluable to have that first year funded to be able to get another grant. I was successful in achieving a CRUK funded clinical doctoral fellowship – which I wouldn’t have got without the BHP fellowship. The support and training was great, but you only get out what you put in – really it gives you the chance to really spend time on your research and make connections within the University. I think there could be a bit more peer-to-peer mentorship, but we are working on that so watch this space!

Has the Fellowship helped with any challenges you might have experienced while completing your PhD?

Getting your first research fellowship or grant is really hard. I failed several times before being successful with the BHP fellowship. So the best thing I got from the fellowship was the confidence that I could make my project work and that others believed in me and my research. My first year in basic science research was challenging, so the fellowship taught me a bit of resilience and determination.

Has the Fellowship benefited your career or opened up other opportunities besides the PhD?

Any career is a constant progression, and none more so than a clinical academic career. These days when I talk to students, I try and make them understand that its not just about climbing the ladder, it is about enjoying each rung and getting the most out of each stage of your training. I view my PhD as a continuum of the BHP fellowship, and indeed my training as a whole. While we all want a good paper from our PhD, it isn’t really about what you’ve done or discovered, it is about your journey and learning from mistakes on the road to research independence. In that sense the fellowship has enormously benefited my career, but its only a piece in a big puzzle and I’ve been learning along the way. Although, it has to be said, I didn’t know that at the start so my focus at the time was to get maximum research output from one year and move on – that attitude has now changed.

What do you plan to do next?

I finished my PhD a few months ago and I have just started an NIHR-funded Academic Clinical Lecturer post in the University. This allows me to spend half my time on research, while still getting the chance to operate and complete my training. I’ve always been interested in teaching and training, so I am always trying to help others and give something back to the programme.

Last time we asked what advice you’d give to someone applying for the fellowship. This time, what advice would you give to someone on the programme – how should they prepare for their post-fellowship career?

  1. Plan ahead, BUT not too far ahead. Don’t lose sight of the short-term goals you need to achieve.
  2. Having said that, always start planning ahead early!
  3. The project you start with, either a fellowship or PhD, will likely not be the one you finish with. Things will almost certainly go wrong, so have a plan B, C, D….
  4. Finally, take the time to make friends and nurture research connections within the University. Both at your level and mentors just above you. Research is always a team effort.

Researchers make mini ‘bone-marrow-in-a-dish’ to test cancer treatments

Written by Louise Stanley on . Posted in Cancer outcomes, Experimental medicine.

Scientists from BHP and Oxford University have made the first bone marrow ‘organoids’ that capture the key features of human bone marrow. The technology, for which University of Birmingham Enterprise has filed a patent application, will allow for the screening of multiple anti-cancer drugs at the same time, as well as testing personalised treatments for individual cancer patients.

A study, published in the journal Cancer Discovery, describes the new method; a process resulting in the production of an organoid that faithfully models the cellular, molecular and architectural features of myelopoietic (blood cell producing) bone marrow.

The research also showed that the organoids provide a micro-environment that can enable the survival of cells from patients with blood malignancies, including multiple myeloma cells, which are notoriously difficult to maintain outside the human body.

First author Dr Abdullah Khan, a Sir Henry Wellcome Fellow at BHP founder-member the University of Birmingham, said: “Remarkably, we found that the cells in their bone marrow organoids resemble real bone marrow cells not just in terms of their activity and function, but also in their architectural relationships – the cell types ‘self-organise’ and arrange themselves within the organoids just like they do in human bone marrow in the body.”

A cross section of a mini bone marrow organoid, showing cells that produce blood platelets, in a network of blood vessels. Credit: Dr A Khan, University of Birmingham

This lifelike architecture enabled the team to study how the cells in the bone marrow interact to support normal blood cell production, and how this is disturbed in bone marrow fibrosis (myelofibrosis), where scar tissue builds up in the bone marrow, causing bone marrow failure. Bone marrow fibrosis can develop in patients with certain types of blood cancers and remains incurable.

Senior study author Professor Bethan Psaila, a haematology medical doctor as well as a research Group Leader at the Radcliffe Department of Medicine, University of Oxford, said: “To properly understand how and why blood cancers develop, we need to use experimental systems that closely resemble how real human bone marrow works, which we haven’t really had before. It’s really exciting to now have this terrific system, as finally, we are able to study cancer directly using cells from our patients, rather than relying on animal models or other simpler systems that do not properly show us how the cancer is developing in the bone marrow in actual patients.”

Dr Khan also added: “This is a huge step forward, enabling insights into the growth patterns of cancer cells and potentially a more personalised approach to treatment. We now have a platform that we can use to test drugs on a ‘personalised medicine’ basis.

“Having developed and validated the model is the first crucial step, and in our ongoing collaborative work we will be working with others to better understand how the bone marrow works in healthy people, and what goes wrong when they have blood diseases.”

Dr Psaila added: “We hope that this new technique will help accelerate the discovery and testing of new blood cancer treatments, getting improved drugs for our patients to clinical trials faster.”

Two BHP members deepen collaboration to improve health provision

Written by Louise Stanley on . Posted in Birmingham Health Partners.

Aston University and Birmingham Women’s and Children’s NHS Foundation Trust (BWC) – both members of BHP – have deepened their strategic relationship by signing a Memorandum of Understanding to co-develop paediatric health initiatives.

The MoU also aims to develop the health services workforce of the future together, with a specific focus on course development and delivery, including placements. It will invest in shared posts that enable closer links between academia, education and healthcare provision, while also supporting honorary appointments and initiating collaborative projects to develop world-leading research and provision in the field of paediatric health and wellbeing.

Professor Aleks Subic, Vice-chancellor, Raffaela Goodby, BWC Chief People Officer (front row) sign the MoU, accompanied by colleagues from both organisations

The partnership will make the most efficient use of resources and reduce duplication by providing a range of shared services, as well as continuously developing new ways to work together, with a view to supporting innovation in the field of healthcare.

These activities will build on the existing joined up work taking place between Aston University and BWC via BHP, such as shared use of the MRI scanning services in the Aston Institute for Health and Neurodevelopment and joint research projects examining topics including epilepsy in children, eating behaviours and neurodevelopment.

Professor Anthony Hilton, pro-vice-chancellor and executive dean of the College of Health and Life Sciences at Aston University, said: “The signing of this Memorandum of Understanding formalises the existing relationship between our two organisations and represents a strong joint commitment to improving healthcare provision in our city.

“Working collaboratively enables us to bring together world-leading research with outstanding clinical provision, for the benefit of our students, patients accessing BWC services and our city and region. I look forward to developing the many ways in which our organisations can work together to improve healthcare provision in Birmingham.”

Matthew Boazman, deputy chief executive officer of BWC, said: “The partnership between BWC and Aston University represents a wonderful opportunity for us to ensure that Birmingham has access to world-class healthcare provision and that those entering the workforce are as ready as they can be.”