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Improving screening in underrepresented groups for genetic condition with heart complications

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

Researchers from across BHP are collaborating with community groups and Amicus Therapeutics to improve screening and diagnosis of Fabry disease, a rare and inherited condition where complications affect the heart muscle, and can lead to premature death.

Through the project, the team – from University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham – has begun to build advisory groups in collaboration with community leaders, healthcare professionals and patients from black, South Asian and other minority ethnic groups. These advisory groups will support researchers to understand patient perspectives on possible barriers to diagnosis, as well as possible approaches to breaking down these barriers. Once further funding is secured, these approaches will be trialled locally in Birmingham, a super-diverse city.

The incidence rate of Fabry disease in the general population is reportedly around 1 in 100,000, although this is likely an underestimate of its true prevalence. Although Fabry disease is very rare, as a genetic condition, patient’s family members have a higher likelihood of the disease that the wider population. Therefore, family screening and mapping is an important tool to identify more cases.

Identifying Fabry disease is important, since the earlier that a patient is diagnosed the better the prognosis for treatment. There are several therapies available, including enzyme replacement and methods to make the faulty enzyme that causes Fabry disease work better, all of which are more effective if started earlier. Without treatment, patients may develop significant cardiac, renal and cerebrovascular complications.

Project lead Richard Steeds, Honorary Professor of Cardiovascular Medicine and Deputy Director of Clinical Research within the Institute of Cardiovascular Sciences at the University of Birmingham and Consultant in Cardiovascular Imaging at University Hospitals Birmingham, explained: “Previous work has shown that Black, South Asian, and other minority ethnic groups, as well as patients from lower socioeconomic groups, are underrepresented in our clinic in Birmingham, despite it being a very diverse city. This knowledge helped us to identify a need for further research to understand and overcome specific barriers to family screening that are more prevalent within minority ethnic groups. If we can address these barriers, then we can support more people to benefit from beginning treatment for this rare condition sooner. Working with members of different community groups is essential to making this work.”

It is well established that minority ethnic groups face health inequalities from language barriers, lower health literacy and cultural difference that contribute to stigma and fear of discrimination that can impact on help seeking behaviours. These inequalities can lead to poorer health outcomes, so addressing them is vital.

Fabry disease can often take many years and several doctors’ appointments to diagnose because many of the symptoms are also attributed to more common causes. Family screening has the potential to help identify more cases sooner.

Some of this work has been funded through a collaboration project with Amicus Therapeutics.

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Eye-safe laser technology to diagnose traumatic brain injury

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

Researchers from BHP founder-member the University of Birmingham have designed and developed a novel diagnostic device designed for the early detection of traumatic brain injury (TBI), which works by shining a safe laser into the eye.

Described in Science Advances, the technique is dramatically different from other diagnostic methods and is now expected to be developed into a hand-held device for use in the crucial ‘golden hour’ after TBI, when life-critical decisions on treatment must be made.

The device incorporates a class 1, CE-marked, eye-safe laser and a unique Raman spectroscopy system, which uses light to reveal the biochemical and structural properties of molecules by detecting how they scatter light, to detect the presence and levels of known biomarkers for brain injury.

There is an urgent need for new technologies to improve the timeliness of TBI diagnosis, which is a leading cause of death worldwide. TBI is caused by sudden shock or impact to the head, which can cause mild to severe injury to the brain, and although it needs diagnosis and treatment as soon as possible to prevent further irreversible damage, it is hard to diagnose at the point of injury. Additionally, radiological investigations such as X-ray or MRI are very expensive and slow to show results.

Birmingham researchers, led by Professor Pola Goldberg Oppenheimer from the School of Chemical Engineering, designed and developed the novel diagnostic hand-held device to assess patients as soon as injury occurs. It is fast, precise and non-invasive for the patient, causing no additional discomfort, can provide information on the severity of the trauma, and will be suitable to be used on-site – at the roadside, on the battlefield or on the sports pitch – to assess TBI.

The device works by scanning the back of the eye where the optic nerve sits. Because this nerve is so closely linked to the brain, it carries the same biological information in the form of protein and lipid biomarkers. These biomarkers exist in a very tightly regulated balance, meaning even the slightest change may have serious effects on brain health. TBI causes these biomarkers to change, indicating that something is wrong.

Previous research has demonstrated the technology can accurately detect the changes in animal brain and eye tissues with different levels of brain injuries – picking up the slightest changes.

The device detailed in the current paper detects and analyses the composition and balance of these biomarkers to create ‘molecular fingerprints’. The study details the development, manufacture, and optimisation of a proof-of-concept prototype, and its use in reading biochemical fingerprints of brain injury on the optic nerve, to see whether it is a viable and effective approach for initial ‘on-scene’ diagnosis of TBI.

The researchers constructed a phantom eye to test its alignment and ability to focus on the back of the eye, used animal tissue to test whether it could discern between TBI and non-TBI states, and also developed decision support tools for the device, using AI, to rapidly classify TBIs.

The device is now ready for further evaluation including clinical feasibility and efficacy studies, and patient acceptability.

The researchers expect the diagnostic device to be developed into a portable technology which is suitable for use in point-of-care conditions capable to rapidly determine whether TBI occurs as well as classify whether it is mild, moderate or severe, and therefore, direct triage appropriately and in timely manner.

BHP members join new Mission for mental health research

Written by Louise Stanley on . Posted in Clinical trials, Early diagnosis and detection, Mental health.

BHP members the University of Birmingham, Birmingham Women’s and Children’s NHS Foundation Trust and Birmingham & Solihull Mental Health NHS Foundation Trust, are part of the Government’s new Mental Health Mission – designed to develop radical new treatments for mental health conditions.

The £42.7M investment into research aims to improve the speed and accuracy of diagnosis and increase the use of new technologies, as well as novel and targeted treatment approaches for those with mental illnesses – including young people at Forward Thinking Birmingham (FTB), the city’s unique 0-25s Youth Mental Health Service.

The Mission will be delivered through the National Institute for Health and Care Research (NIHR) Mental Health Translational Research Collaboration, a UK wide network of leading investigators specialising in mental health research.

In Birmingham, £9.9 million in funding will enable the establishment of the Midlands Translational Research Centre of Excellence, co-led by the Universityof Birmingham with Birmingham Women’s and Children’s Hospitals and Birmingham & Solihull Mental Health NHS Foundation Trust, with reach across the Midlands through the five years’ funding.

Research will focus on increasing recruitment to new studies to test and validate treatments in early psychosis, depression and children and young people. We will work with people with lived experience to comprehensively understand the best way to test novel treatments. There are also plans to train and support a network of new researchers, partners, NHS staff and young people in the Midlands.

Professor Rachel Upthegrove, Professor of Psychiatry and Youth Mental Health at the University of Birmingham and Mental Health Research and Development Lead at Birmingham Women’s and Children’s NHS Foundation Trust, said: “We’re delighted that the Government is making such a significant investment in mental health research. This funding will allow us to increase and lead large-scale early intervention trials aimed at delaying or preventing the onset of severe mental illness, and its impact, with evidence-based treatments and support.

“The Centre will put research where we need it most, focusing on young, superdiverse, and deprived populations, which may be unfairly missing out on access to research.”

Teams at the Research Centre will work with individuals with lived experience to understand the best way to test treatments. There are also plans to train and support a network of new researchers, partners, NHS staff and young people in the Midlands.  

Building on the priority healthcare missions launched in November 2022 as part of the Life Sciences Vision, the Mental Health Mission will promote collaboration across different sectors to bolster research and attract further investment from industry and research organisations.

Nationally, the Mental Health Mission will be chaired by Kathryn Abel and Husseini Manji. In a joint statement, they said: “We are delighted to be working together to make the new Mental Health Mission a truly revolutionary force behind mental health research. We want the Mission to create tangible differences to the lives of patients, both in the UK and internationally. Between us, we bring a wealth of experience in mental health research and innovation, and a commitment to genuine collaboration with patients, industry and healthcare staff.

“Bringing together the public sector, patients and industry as equal partners, the Mission will work with the Office for Life Sciences and the National Institute for Health and Care Research (NIHR) to support the NHS and NIHR to capitalise on its size and scope, and on the depth of its data resources. Alongside additional investment in mental health research and infrastructure, the Mission will foster a step change in the way we think about mental health, mental illness and its treatment. This will support development of the critically needed treatments across the spectrum of mental illness.

“We want the UK to be the most attractive place to conduct robust, high impact mental health research, ensuring people have access to the best, and newest, treatments. We are confident that the Mission will be unique in its ability to convene and challenge national partners to make this happen.”

 

£2m study aims to improve early stage ovarian cancer diagnosis

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

A £2 million study will see an advanced test used at GP surgeries in the West Midlands to diagnose early-stage ovarian cancer – potentially saving thousands of lives a year.

The project involves BHP members Sandwell and West Birmingham (SWB) NHS Trust and the University of Birmingham collaborating with Walsall Healthcare NHS Trust (WHT) and primary care provider Modality, to offer a blood test called ROMA to patients experiencing symptoms of ovarian cancer.

Signs of the disease include bloating, stomach pain, needing to urinate more often and always feeling full.

If symptoms persist or are severe, frequent or out of the ordinary, women are urged to see their GP where – usually – a CA-125 blood test will be carried out, which has around a 50% detection rate of early-stage cancer.

However, the advanced ROMA test used during this trial at Modality-run GP services in Walsall, Sandwell and West Birmingham, will identify key markers of this particular disease at an earlier stage.

If a patient has tested positive, they will be referred to their local Trust to attend a new one stop clinic where they’ll see a consultant, undergo a specialist scan and then a further consultation where the results will be shared. They will be referred for further treatment if needed.

Speaking about the study, called SONATA (tranSforming Ovarian caNcer diAgnostic paThwAys), Sudha Sundar, Professor of Gynaecological Cancer at the University of Birmingham and Consultant Surgeon at SWB NHS Trust, said: “Ovarian cancer is rare and there is a need to increase the understanding and awareness of the symptoms associated with it among our population and GPs.

“We know that 90% of women diagnosed with ovarian cancer at stage one will survive, but this drops drastically to 15% if it is picked up during stage four.

“Research conducted with my team at the University of Birmingham found out that the ROMA test is significantly better than current tests (CA125 and ultrasound) used in both pre and postmenopausal women*.

“A previous study had found that the ROMA test detects up to 20% more early-stage cancers than the current test which only picks up 50% of early-stage cancers**. We are putting this research into practice by carrying out this trial.”

“With Modality-run GP surgeries trialling the ROMA test we will be able to establish if it is acceptable to patients and clinicians. By testing many samples across two large laboratories, we will be able to confirm whether the ROMA test has a higher chance of detecting this cancer earlier than the current CA-125 blood test used and whether implementing this across the NHS will be cost-effective.”

Leading on the project, Dr Aamena Salar, medical director for Modality Partnership Community Services, said: ‘Our aspiration is to transform the care of ovarian cancer by earlier detection and better outcomes for our patients.”

Nina Jhita, programme director at Modality, added: “This is true innovation; we (primary care) are delighted to collaborate with key system partners across the West Midlands to really make a difference to the lives of women while demonstrating how this solution can be scaled across the UK.”

The final part of the study will see 41,000 primary care samples sent to the Black Country Pathology Service and South Tyne and Wear laboratories to accurately establish whether using the ROMA test rather than CA125 will be cost effective for the NHS. The results from the study, funded by the NHS Cancer Programme and the Small Business Research Initiative, will be analysed and used to change the way this cancer is diagnosed in the future.

Professor Sundar added: “It’s an exciting study which is a great example of integrated working between all the organisations involved. We are looking forward to finding out the results so that we can change the way this cancer is detected in the future and drastically improve survival rates.”

*Abstract published in July 2023: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011964.pub2/full
**Further information can be found here: https://pubmed.ncbi.nlm.nih.gov/27540691/

Funding boost for Birmingham rare disease research

Written by Louise Stanley on . Posted in Birmingham Health Partners, Clinical trials, Early diagnosis and detection, Experimental medicine.

BHP founder-member the University of Birmingham has been awarded a £500k Pathfinder Award from the medical research charity LifeArc which will support early-stage projects with a focus on translational development in rare diseases.

The successful projects have now been announced following an internal selection process. Research, conducted by the University of Birmingham and working across Birmingham Health Partners, will begin this spring.

Professor Timothy Barrett, Director of the Centre for Rare Disease Studies (CRDS) Birmingham, commented: “I am thrilled that our Centre for Rare Disease Studies at the University of Birmingham has been successful in securing a LifeArc Pathfinder Award. We are working closely with other organisations from Birmingham Health Partners; Birmingham Children’s and Women’s Hospital and University Hospitals Birmingham; to fund a number of impactful translational research projects through the fund. Our uniquely diverse patient population, and strength in partnership ensures that we are in the best possible position to drive forward research in rare diseases to accelerate progress and ultimately improve patients’ lives.”

Around the world, approximately 300 million people are living with a rare disease. A disease is considered rare if it affects less than 1 in 2000 people. Around 80% of rare diseases have a genetic component. They are often chronic, progressive, degenerative and frequently life-threatening with no existing cure.

Owing to the nature of rare disease, small patient populations make research challenging. Lack of scientific knowledge and quality of information on rare diseases can mean that misdiagnosis is common and treatment options may be limited.

The Centre for Rare Disease Studies supports basic and applied research, in order to build a pipeline of translational research from gene discovery to improving the diagnosis, clinical management and treatment of these disorders.

Research projects that will benefit from the Pathfinder Award include:

      • The NEEDED Study (NanoporE Enhances Diagnosis in rarE Disease), led by Dr Hannah Titheradge, which will investigate the effectiveness of a new type of genome sequencing to identify rare diseases.
      • A proof-of concept study, led by Dr Nekisa Zakeri, which aims to develop a novel ‘off-the-shelf’ T cell immunotherapy capable of providing more effective treatment for patients with a rare liver cancer.
      • The CATCH Study (CArbalivefor the Treatment of CHoleastic Disease), led by Dr Palak Trivedi, looks into whether a new medical device can absorb toxins from the gut to reduce inflammation and scarring in primary sclerosing cholangitis; a rare progressive liver disorder for which no medical treatment has been shown to slow disease progression.
      • Dr Richard Tuxworth and Professor Zubair Ahmed, whose research in DNA damage in nerve cells has already resulted in patent applications covering pathways and mechanisms that could provide new therapies for neurological conditions and spinal cord injury, will now work with Professor Andrew Beggs and Dr Chiara Bardella to investigate the potential for one of these pathways (the ATM-Chk-2 pathway) as a basis for therapies to tackle rare neurological conditions that appear early in childhood.
      • Dr Sovan Sarkar’s study aims to improve the health of patients with rare childhood-onset forms of neurodegeneration by correcting the process of autophagy that normally removes undesirable cellular materials which is detrimental to brain cells called neurons.

Dr Hannah Titheradge, a Consultant in Clinical Genetics at Birmingham Women’s and Children’s NHS Foundation Trust, will investigate the effectiveness of nanopore sequencing – a new type of real time genome sequencing – on a larger group of patients. Previously tested on a very small sample, this new technology showed promise for improving our capability to diagnose rare diseases.

Nanopore sequencing reads more letters in an individual’s genome than the standard sequencing method used to diagnose rare genetic disorders. The NEEDED Study (NanoporE Enhances Diagnosis in rarE Disease) will explore a more detailed approach that could improve the percentage of patients who receive an important genetic diagnosis, which can help those patients and their families face their challenges feeling better informed.

Dr Hannah Titheradge commented: “Receiving a diagnosis can be an uphill challenge for patients with rare diseases and their families. These individuals often wait years for a final diagnosis, having undergone multiple tests and procedures. Having a diagnosis is very important because it helps these individuals better understand their health problems and plan for the future. Some genetic conditions are treatable, and a diagnosis is the first step towards accessing these treatments. We can also understand whether any other family members’ health may be affected. For these reasons, any advance that can be made in improving rare disease diagnostics is invaluable.”

Samira Fakire, Business Manager at LifeArc, added: “We hope that the Pathfinder Award will encourage more researchers to move into the rare disease space and promote the development of a translational culture – pushing more discoveries from the lab into meaningful real-world benefits for patients.”

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).