Author: Louise Stanley

New research collaboration will develop precision cell therapies for blood disorders

Written by Louise Stanley on 19/05/2022. Posted in Cancer outcomes, Experimental medicine, Health inequalities.

The Universities of Birmingham and Oxford are to take part in one of five NHS Blood and Transplant (NHSBT) research units launched today.

The £20m programme, co-funded by the National Institute for Health and Care Research (NIHR) and NHSBT – is aimed at providing new technologies, techniques or insights that will benefit donation, transfusion, and transplantation. The NIHR BTRUs are partnerships between universities and NHSBT.

Many of the work strands in the new units could result in new technologies and practices that can then be delivered at scale by NHSBT, helping to save and improve even more lives. Much of the work will be aimed at reducing health disparities and improving access to new treatments.

Researchers at the Universities of Birmingham (UoB) and Oxford are part of the NIHR BTRU in Precision Cellular Therapeutics – also working in collaboration with University Hospitals Birmingham (UHB) NHS Foundation Trust. UoB and UHB are both founding members of BHP, with a long history of collaborative research and development.

The aim is to develop new kinds of cell therapies for blood disorders and blood cancer, and improved systems for following up patients receiving treatment to better support their care.

There is a wide range of work in the package but examples include:

- Transplants work in blood cancer patients because some of the donor immune cells attack and eliminate the cancer, but these cells can also attack the donors own cells and cause a complication called graft versus host disease (GvHD). The team will seek to identify and clone the receptors that enable the T cells to target the cancer cells while reducing the toxicity due to GvHD seen in patients. The ultimate aim of this research is develop a novel clinical trial, with NHSBT, via its cell therapy manufacturing infrastructure, expanding these cancer specific T cell receptors for use in patients.
- There is a shortage of suitable cell donors for minority communities. Cord blood units from babies may be a match but not have enough cells to be successful in adults. The team will seek to expand and gene edit the stem cells in cord blood, so they could be used with increased safely in a wider range of adults. NHSBT will support the translation of this research through to early phase clinical trials, providing process development, manufacturing and quality control expertise. This initiative will drive wider access to cord blood transplant.
- It is important that patients from all communities benefit from cell therapies. The team will seek to better understand how patients access the newer cell therapies and how they perceive the benefits of treatment. The team will develop new digital technologies that improve care by enhancing interactions between the patients and their doctors and nurses.

The BRTUs are funded by £16m from the NIHR and £4m from NHSBT, with research goals set to meet NHSBT’s requirements, to be delivered between 2022 and 2027.

The products could be manufactured at the latest NHSBT sites including major new centres such as the new cellular therapies laboratories in Barnsley and the forthcoming Clinical Biotechnology Centre in Bristol.

Dr Gail Miflin, Chief Medical Officer for NHSBT, said: “By collaborating with academia, these five new Blood and Transplant Research Units will help us to deliver on our mission to ‘save and improve even more lives’ and drive innovation to inform future clinical practice and improve patient outcomes.

“For example, the supply-demand gap for solid organs continues to grow. We will explore the use of organ perfusion technologies to maintain and enhance the quality of organs, improve organ preservation and increase organ utilisation. This will enable more patients to receive the transplant they need.

“And by building and analysing new data sets to track and demonstrate the impact of our interventions will lead to better understanding and improved outcomes. We already do this well for solid organs, but do not currently understand the outcomes for people who receive blood or stem cells. We will work with partners to build integrated data sets for these patients, focusing on the multi-transfused, especially those with sickle cell disease where a clear health inequity exists.

“To maximise the value and impact from our research, we will accelerate the translation of innovation into practice. The NIHR BTRUs will be an important vehicle for this in the longer term.”

BHP welcomes new Professor of Regenerative Medicine

Written by Louise Stanley on 16/05/2022. Posted in Experimental medicine.

Professor Ivan Wall has been appointed as Professor of Regenerative Medicine with the Institute of Immunology and Immunotherapy at BHP founder-member the University of Birmingham.

Professor Wall joins us from Aston University and has a well-established relationship with the University of Birmingham as the Lead for the Centre for Advanced Therapies Manufacturing Training. His research group works on stem cells and extracellular vesicles, with emphasis on industrial translation and scale up production – his ambition is to see Birmingham become a hub manufacturing cell and gene therapies that local patients can benefit from.

To mark Professor Wall’s latest appointment with the University, the Institute of Immunology and Immunotherapy sat down with him to learn more about his background and expertise:

What research and industry work do you currently undertake?

My academic research spans stem cells, tissue engineering and bioprocessing. I am particularly interested in the role of mesenchymal stem cells in regenerative medicine, both via direct differentiation towards regenerative cell types but also via their secretion of paracrine signalling vehicles such as exosomes. Exosomes enable cells to communicate with each other and current research points to stem cell-secreted exosomes as important cues for regeneration of injured tissues. My research team has created novel cell lines, demonstrated scalable production and examined cell stimulation methods to enhance potency. Outside of academia I have co-founded two companies: FourPlus Immersive, which creates virtual reality training simulations for GMP cell and gene therapy manufacturing; and Quest Meat. Both companies are based in Birmingham.

What made you become interested in regenerative medicine?

I undertook a PhD in wound healing and my early research focussed on understanding why some wounds in aged or diabetic patients do not heal very well. This spurred an interest in how stem cells are the building blocks for tissue and organ formation, with the aim of understanding how stem cells might be used to drive regeneration of aged or injured tissues. In 2009 I became a lecturer at UCL, working in regenerative medicine bioprocessing, which enabled me to bring together my interest in working with stem cells to treat disease with industrialisation strategies to scale up production for clinical applications.

What is Quest Meat and how did you come about co-founding this organisation?

Quest Meat is a startup that is creating cultivated meat. I co-founded this company with Dr Petra Hanga (now UCL) and former board members of a UK regenerative medicine company and we are based here in Birmingham. We have been able to take our knowledge of scaling up stem cells for medicine and apply it to future meat production. We are doing this because global food production in its current form is not sustainable and, with a growing global population and climate change creating pressure on existing food systems, we need a radical new approach to food production. As a parent I want my children to eat nutritious food that has not been intensively farmed, used antibiotics that may cause health problems, or will accelerate environmental damage. As a scientist and CEO of Quest, I can work with a brilliant team to create a healthy and sustainable alternative.

What are the opportunities and challenges facing future cell and gene therapies?

Cell and gene therapies are transforming healthcare and we are now seeing some truly remarkable treatments emerging that are curing patients of rare and life-threatening diseases, including rare forms of cancer that have not responded to conventional treatments.

Even though these medicines are still in their early days, the rate of development of new treatments means they are becoming more and more prevalent in hospitals and so over time more patients will benefit from them. The main challenge is in being able to manufacture them consistently and affordably, especially as some manufacturing batches only treat a single patient. A second critical challenge is in training enough people to grow the workforce needed for this rapidly growing industry – there is a huge skills shortage. University of Birmingham is at the forefront of addressing these challenges, with the National Training Centre for Advanced Therapies Manufacturing and also excellent advanced therapy manufacturing cleanroom capabilities.

What key advice would you give to researchers considering scaling their research into industry?

Think about what manufacturing for your final product would look like early in the translation cycle. A lot of effort is required to manufacture medicines that will be administered to patients. For example, regulatory guidelines around good manufacturing practice (GMP) must be adhered to, to show that those manufacturing processes consistently deliver the required product quality. Everything from the cleanroom environment, manufacturing equipment, processes and personnel must be monitored and documented. Any changes to manufacturing later on will require re-validation which can cause significant delays to the product development cycle.

Healthy Mum, Healthy Baby, Healthy Future: Report Sets out Vision to Deliver Safe, Effective and Accessible Medicines for use in Pregnancy

Written by Louise Stanley on 11/05/2022. Posted in Birmingham Health Partners, Maternal health.

In a UK-first report launched today, in the House of Commons, leading figures from charity, healthcare, industry, law and academia have outlined a collaborative vision for UK leadership to improve maternal health. The Healthy Mum, Healthy Baby, Healthy Future: The Case for UK Leadership in the Development of Safe, Effective and Accessible Medicines for Use in Pregnancy report proposes a clear roadmap to improve the lives of millions of people, not just for women while they are pregnant, but for future generations.

Download the report Healthy Mum, Healthy Baby, Healthy Future: The Case for UK Leadership in the Development of Safe Medicines for Use in Pregnancy [PDF, 2mb]

Globally, over 800 women and 12,000 newborns die every day from preventable pregnancy-related complications – that is one woman and 17 babies every 2 minutes. Pregnancy complications affect two lives in one short period of time, yet only two medicines have ever been developed specifically for pregnancy-related conditions, and not a single new medicine for some of the most serious pregnancy-specific conditions has reached women in decades.

Over the past year, a Birmingham Health Partners led Policy Commission – co-chaired by Baroness Manningham-Buller, Co-president of Chatham House and Professor Peter Brocklehurst, University of Birmingham – has heard from key stakeholders on how best to develop safe, effective and accessible medicines for use in pregnancy. Compelling evidence gathered throughout the process has informed eight critical recommendations which, if implemented by government, will successfully prevent needless deaths and find new therapeutics to treat life-threatening conditions affecting mothers and their babies.

Key proposals include strengthening the UK’s research capabilities to address gaps in our biological knowledge; more effective clinical trials support; and harnessing collaborative partnerships between government, universities and the pharmaceutical industry. Importantly, the report advocates for women who have been historically excluded from clinical trials to be a vital part of future research, ensuring they are not left behind and can benefit from modern medical advances. The UK, with its existing track record of pregnancy research, and lifelong NHS health records, is uniquely placed to lead this overdue and vital reform, working alongside global partners to deliver real change.

Commenting on the report, Co-chair, Baroness Manningham-Buller LG, DCB, FMedSci said: “When I was asked to become joint chair of the Commission that has produced this report, I am ashamed to say that I wasn’t aware that there was an acute problem. Despite being at Wellcome for twelve years and Imperial College for six, I had no idea that research into conception and pregnancy was largely neglected and that virtually no drugs had been developed and trialled for pregnant women in the many decades since thalidomide. This leaves women at the mercy both of general diseases, the diseases of pregnancy and drugs which are usually unlicensed. The evidence taken by the Commission in its inquiry convinces us that this urgently needs to change. We suggest how.”

Co-chair, Professor Peter Brocklehurst said: “This report represents a clear and timely platform to improve the care we provide to pregnant and breastfeeding women, by increasing the availability of safe, effective and accessible medicines for their use. The Commission’s role was to provide a blueprint for action and will provide ongoing support in implementing the recommendations set out in this report, as there is an urgent need for action to address this underserved area of medical need. Without it, women and babies will continue to die when they could be saved. They will continue to experience long-term health effects, disability and distress, which might be avoided.

“We strongly urge the scientific, clinical, industry, regulatory, governmental and public sectors to come together to address the recommendations of this Commission. The UK has the opportunity to transform maternal health across the world, improving the lives of mothers, their babies and future generations – let’s not waste it.”

Yasmin Golding, campaigner from the Epilepsy Society, who continues to be affected by the lack of safe and effective medicines said: “As a mixed race woman with epilepsy there are pregnancy risks I cannot avoid, but many I should be able to in the age of modern medicine. This report gives me and other women hope that in the future they will be able to spend more time enjoying pregnancy and less worrying about avoidable risks that threaten them and their baby.”

Sandra Igwe, founder of The Motherhood Group and Co-chair of the National Inquiry into Racial Injustice in Maternity Care welcomed the report by saying: “Giving a voice back to those who are ultimately the most affected is crucial, and an imperative step for us mothers advocating for ourselves. All women, regardless of race, age, and socioeconomic background should be allowed to have safe and effective medicine during their pregnancy. It’s key in building trust, offers more choice, and lowers potential health risks – a springboard in the right direction. These recommendations will specifically further help women like me, who due to the colour of our skin, face health inequalities within maternity care.”

Find out more about Birmingham’s holistic and collaborative approach to maternal health research on our new research spotlight page

Improving access to quality post-injury care can save lives

Written by Louise Stanley on 11/05/2022. Posted in Health inequalities.

A major study led by BHP founder-member the University of Birmingham will help reduce unnecessary deaths in developing countries from injuries caused by accidents or violence.

Every year five million people die due to injuries like road traffic accidents, burns, falls, or violence – with 90% of these deaths in Low- or Middle-income Countries (LMICs).

Backed by £2.9 million of NIHR funding, University of Birmingham (UK) and University of Stellenbosch (South Africa) researchers will build on partnerships with experts in Ghana, South Africa, Rwanda, and Pakistan to explore how to overcome barriers to accessing quality care after injury and reduce the likelihood of death or disability.

Experts will use a ‘four delays framework’, which looks at where delays occur in people seeking, reaching, receiving, and remaining in good quality care after injuries, to collect information on delays and their effects on patient outcomes. They will develop visualisations for policy makers to see where to intervene to reduce delays suffered after injury and produce maximum health benefits.

The project builds on a recent study funded by the NIHR led by University of Birmingham and experts in Rwanda which identified 121 barriers to access to quality injury care in three countries across sub-Saharan Africa: Ghana, South Africa and Rwanda.

Researchers discovered that whilst there were a large number of barriers in total, only 31 (25.6%) of these were shared across all three countries, suggesting that solutions to improve access to quality care after injuries may be highly contextually dependent.

Also, only just over half of these common factors (18/31, 58%) were related to delays in receiving quality care at the healthcare facility, suggesting that investment needs to be made in overcoming delays in seeking or reaching care.

Justine Davies, Professor of Global Health Research at the University of Birmingham, explained: “Injuries in LMICs are common and their number is expected to increase, but death and disability after injury can be substantially reduced if people reach healthcare facilities in a timely manner. Understanding access to quality injury care is critical to improving patient outcomes. By partnering with organisations in Ghana, South Africa, Rwanda, and Pakistan, we will develop solutions for future study in these, and similar countries. Our research has already identified many barriers to quality care in Rwanda, Ghana and South Africa. However, as few of these are shared across countries, solutions to reduce the risk of post-injury death and disability will need to reflect circumstances in each country.”

The diversity of cultures, economies, and injuries in partner countries will allow researchers to identify delays and solutions that can be applied across different settings and others that are transferable outside of the four countries of this study.

Study leaders will also train four PhD students and 14 junior researchers in countries with low resources. Training will be done through the development of research hubs in partner countries – these hubs will continue and train future LMIC researchers beyond the project’s end.

Researchers will also work closely with patients, community members and leaders, healthcare providers, and policy makers to understand how to translate the findings of the study into real world solutions.

Patient symptom and quality of life assessments must be inclusive and equitable

Written by Louise Stanley on 09/05/2022. Posted in Health inequalities.

Information reported directly by patients can be invaluable for assessing the impact of disease and treatment on patients’ symptoms and quality of life -but more needs to be done to include under-served groups to avoid rising inequalities in healthcare, say experts at BHP founder-member the University of Birmingham.

The information is commonly collected in both clinical trials and clinical practice and ensures that the patient’s perspective is at the heart of decision making. As use of these data become more commonplace, however, researchers in the University’s Centre for Patient-Reported Outcomes Research are calling for more to be done to ensure such information can be provided by everybody.

In an article published 5 May 2022 in Nature Medicine, researchers in collaboration with patients, regulators and international experts identify some of the barriers to participation such as access to technology, disability, language and cultural requirements and call for these to be addressed.

Lead author, Professor Melanie Calvert, said: “When we start to embrace new approaches to healthcare, such as use of patient-reported outcomes, we need to make sure that barriers to participation are addressed at an early stage. If we don’t do this, the gaps between advantaged and disadvantaged populations will only get worse.

“Representative diversity in clinical trials is vital to ensure new medicines and technologies are applicable to the population they are intended to serve. Targeted initiatives are needed to ensure that no groups are excluded from participation in patient-reported outcome data collection, both in research settings and routine clinical care.”

Specific recommendations in the article include:

- - Improve diversity by involving individuals who represent target populations when designing patient questionnaires.
  - Consider the type and severity of disease when seeking patient views, including cognitive or functional impairment that would limit participation.
  - Be aware of cultural needs or languages that might be a barrier, and address these sensitively and appropriately.
  - Include individuals with all levels of reading, writing and problem solving abilities by ensuring material is accessible and that assistance is available, if required.
  - Provide alternative methods of participation to promote digital inclusion
  - Where information is being used in drug development, make sure inclusivity is included early on in discussions about data collection.

Rav Verdi, a patient partner who co-authored the work, said: “As a patient and living in a cosmopolitan society it’s encouraging to see that all walks of life have been considered and a means of communication thought about to glean information from the patient and to provide information to the patient regarding their care and treatment. As worldwide issue, information could be shared with treatment centres to provide better care and understanding of different groups of the population.”

Roger Wilson, a patient partner adds: “Listening to patients reveals the range of diversity which must be understood and allowed for by careful design if a study is to offer benefits to society equitably.”

Professor Calvert adds: “Patient-reported outcome measures and data collection must be reflective of diverse and multicultural societies, to improve research and promote equitable clinical care for the benefit of all patients and the public as a whole.”

The team are supported by a number of funders including the National Institute for Health and Care Research (NIHR) Biomedical Research Centre Birmingham and Applied Research Collaboration West Midlands, Health Data Research UK and UK SPINE.

Revolutionary technology has potential to help children with asthma

Written by Louise Stanley on 05/05/2022. Posted in Inflammation and chronic disease.

BHP members Birmingham Women’s and Children’s Hospitals have initiated a new study which could potentially revolutionise care for young people with asthma using artificial intelligence technology.

Over the next two years, 50 children and families will take part in the Childhood Home Asthma Monitoring Study (CHAMP), which uses a small table-top electronic device designed by Albus Health, not dissimilar in size to an Amazon ‘Alexa’ virtual assistant, to personally monitor a child’s symptoms and breathing while they sleep.

Using sensors and a microphone, it measures breathing and heart rate by analysing coughs, wheezing and other noises, while also assessing environmental factors, such as humidity and air pollution levels. The data collected over a period of months will help form a unique and personalised set of triggers which is able to warn of a future asthma attack days before it potentially happens, allowing for action to be taken.

Around one in 11 children in the UK has asthma and it’s one of the most common chronic conditions which causes hospitalisations. The potential of this AI technology is potentially huge; positively impacting thousands in the future.

Dr Prasad Nagakumar, Respiratory Consultant, is the Chief Investigator leading this exciting £1.6million CHAMP study, funded by the National Institute for Health Research. He’s looking forward to working alongside partners including Asthma UK, Imperial College London, Oxford Academic Health Science Network and Royal Brompton Hospital, where patients are also being recruited to take part.

Dr Nagakumar said: “I’m delighted that we’ve now started this exciting study, which has such a huge potential. Over the next two years we’ll be working hard to further understand and develop the use of this innovative monitoring and, importantly, prediction technology.

“Our aim is to build algorithms and clinical-supporting tools for the early detection of asthma attacks in children by capturing warning signs before patients or those giving care perceive them.”

Professor Jeremy Kirk, Clinical Director NIHR Clinical Research Network (West Midlands) and Research and Innovation Director at our Children’s Hospital, said: “Asthma is the most common chronic disease in childhood and blights many lives. This project utilises the very newest cutting-edge technologies to give us further understanding of this condition, hopefully enabling better monitoring, optimal care and a reduction in hospital admissions.

“Dr Nagakumar and the team are to be congratulated on being awarded this highly competitive and prestigious grant.”