Author: Louise Stanley

Urine test for bladder cancer to be developed by University of Birmingham and Nonacus

Written by Louise Stanley on 01/07/2021. Posted in Cancer outcomes, Early diagnosis and detection.

BHP founder-member the University of Birmingham and Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, have partnered to develop a non-invasive test for bladder cancer. The test, which is expected to be available by mid-2022, will use highly sensitive liquid biopsy technology developed by Nonacus, and a panel of biomarkers validated by Dr Rik Bryan and Dr Douglas Ward from the University’s Bladder Cancer Research Centre, to diagnose the disease from urine samples.

Bladder cancer is the seventh most common cancer in the developed world¹. In the UK, over 100,000 people a year are referred to hospital clinics that investigate for bladder cancer, usually after passing blood in their urine (haematuria). The first stage of investigation is usually cystoscopy, which involves inserting a camera into the bladder. Of these 100,000 patients, around 12% are subsequently diagnosed with bladder cancer, normally after a second invasive procedure to extract a biopsy.

Dr Bryan, Director of the Bladder Cancer Research Centre, commented: “While blood visible in the urine should always be investigated, over 80% of people who have a cystoscopy at a haematuria clinic are diagnosed with non-malignant conditions or have no abnormality. Unfortunately, the remaining 20% will need a further invasive procedure to confirm diagnosis. What is required is a highly sensitive and specific, non-invasive test that can rapidly determine those who need a biopsy and those who do not, and a urine test is the obvious place to start.”

While the ‘liquid biopsy’ approach is attractive, the low levels of tumour DNA in a background of DNA from normal tissues requires highly sensitive analytical techniques to obtain accurate results. However, researchers at the University started their work in the knowledge that Nonacus had successfully pioneered commercial non-invasive prenatal tests to identify low-levels of fetal DNA in maternal blood samples. Moreover, the company was developing methods to allow confident and sensitive calling of mutations from as little as 10ng of DNA.

The researchers used ‘deep sequencing’ of tumour DNA to identify mutations that are present in the majority of urothelial bladder cancers (UBCs). Their work, which was funded by Cancer Research UK and an MRC Confidence in Concept grant, involved sequencing 23 genes from tumour samples collected from 956 newly diagnosed, treatment-naïve patients. This deep sequencing of genes identified 451 unique mutations that were present in over 96% of tumours. The researchers also demonstrated that these mutations were identifiable in urine samples collected at the same time as tumour sampling².

As the researchers have shown, mutated DNA in a urine sample can be extracted from cancer cells shed into the urine from the lining of the urinary tract, or can be found as cell-free DNA fragments. However, extracting DNA from the cancer cells provides more reliable amounts of DNA for the test, especially when only small volumes of urine may be available. Coupling the mutation panel with the unique molecular identifiers and the proprietary target capture technology provided by the Nonacus Cell3 Target™ will provide a much more sensitive test than the existing PCR-based approach. The researchers are already working on validating this combination in a further 600 cases (including non-cancer cases) and they expect to publish data on sensitivity and specificity within six months.

Nonacus intends to launch the new bladder cancer test within 12 months, and the final product will include access to bioinformatics software to help with analysis. The company expects the test will provide high sensitivity for all stages and grades of disease, and will ensure the test is available worldwide to laboratories, hospitals and clinics.

Promisingly, the original research also determined the influence of the mutations on cancer progression, time to recurrence, and overall and disease-specific survival in patients with non-muscle-invasive bladder cancer (NMIBC), and disease-specific survival in patients with muscle-invasive bladder cancer (MIBC), raising the possibility that the test could be used to stratify patients according to risk.

Chris Sale, CEO of Nonacus Ltd, commented: “We expect this partnership to deliver better care and outcomes for patients by reducing the number of invasive procedures, providing earlier diagnosis and speeding up access to treatment for people with bladder cancer.”

Tony Hickson, Chief Business Officer at Cancer Research UK, said: “As funders of much of the world-class, cutting-edge cancer research happening in the UK, we offer unique opportunities to commercial partners looking for early involvement in new discoveries. Having Nonacus on board to help transform promising findings in the lab into a new non-invasive test to diagnosis bladder cancer is a testament to how commercial collaborations have the potential to transform the lives of patients. We are looking forward to seeing the next steps as the test is developed and rolled out to the UK and beyond.”

Allen Knight, Chair of Trustees, Action Bladder Cancer UK, said: “This really is very exciting and has the potential to make an incredible difference for patients and for Bladder Cancer treatment. Currently urine tests do not accurately pick up bladder cancer, and invasive tests are required to confirm a diagnosis. A urine test that can rapidly determine who needs these tests will be a very welcome development. Many patients, myself included, find cystoscopies very uncomfortable at best, and they can have lasting side effects. This research could pave the way for routine screening, common in other cancers, but unavailable at present for Bladder Cancer.”

Blood cancer trial sponsored by the University of Birmingham opens for recruitment

Written by Louise Stanley on 28/06/2021. Posted in Cancer outcomes, Clinical trials.

A new Cancer Research UK-funded clinical trial being sponsored by BHP founder-member the University of Birmingham has opened for recruitment – aiming to investigate the efficacy of a novel treatment for patients affected by a specific type of blood cancer.

PROMise, which is being co-ordinated via the Cure Leukaemia-funded Trials Acceleration Programme (TAP) hub at the University of Birmingham’s Cancer Research UK Clinical Trials Unit (CRCTU), will recruit patients aged over 16 who suffer with myelofibrosis (MF).

Over the next two years, 15 NHS centres will recruit MF patients who will be given a novel agent called PLX2853 in addition to the existing standard treatment of ruxolitinib.

Each year in the UK over 300 patients are diagnosed with MF, which is a blood cancer associated with debilitating symptoms including extreme fatigue, pain, weakness and shortness of breath. Around 10-20% of MF patients go on to develop acute myeloid leukaemia (AML) and consequently, a diagnosis of MF has a huge impact on both length and quality of life, with median survival from the time of diagnosis being just two years for patients with high-risk disease.

The only curative therapy for MF is stem cell transplant; however, this is only suitable for a small minority of younger patients who don’t present with comorbidities (the effect of all other conditions an individual patient might have – physiological or psychological).

The current NHS standard of care for those unsuitable for stem cell transplant is treatment with ruxolitinib, approved for use in 2011 and currently the only therapy approved with an indication for MF.

Professor Pam Kearns, Director of the University of Birmingham’s CRCTU, said: “Whilst ruxolitinib is already in widespread clinical use, many patients do not achieve an adequate response. Significant residual symptoms remain in most patients thus there is a major unmet clinical need and the PROMise trial is addressing an urgent need for improved therapeutic approaches for MF patients.”

Chief Investigator, Professor of Haematology at University of Oxford, Adam Mead, said: “The PROMise study is a really exciting study that has just opened in the UK and will be opening across 15 centres. This is introducing a new treatment called PLX2853, in combination with ruxolitinib, for patients with MF. The impact on patients for this combination of treatments, I hope, will be improvement of their symptoms, improvement of their quality of life, without causing them side effects.”

Advanced Therapies Skills Training Network comes to Birmingham

Written by Louise Stanley on 28/06/2021. Posted in Experimental medicine.

The University of Birmingham has been confirmed as the third National Training Centre in the Advanced Therapies Skills Training Network (ATSTN) initiative.

The initiative is designed to develop and deliver specific practical skills to address the growing need in the UK for skills in vaccine and advanced therapy medicinal product (ATMP) manufacturing.

As one of the three initial National Training Centres, BHP founder-member the University of Birmingham will deliver advanced technology courses on-site in collaboration with local companies and institutions to provide training complementary to the ATSTN initiative. These include modules on ATMP manufacturing design and clinical adoption, as well as documentation and implementation of ATMPs, which will be delivered as a combination of on-site, online learning and virtual reality modules.

The first courses will be launched in September 2021 and will cover the fundamental aspects of ATMPs and Good Manufacturing Practice (GMP). The University of Birmingham will also offer master’s degree level modules on GMP standards, which are a vital requirement for the authorisation, manufacture, and commercialisation of ATMPs.

Professor Phil Newsome, Director of Research in the College of Medical and Dental Sciences at the University of Birmingham, commented: “We are delighted to provide our leading expertise, playing such a pivotal role in delivering these much-needed skills for the UK’s advanced therapies sector. This collaboration between industry and academia will create a truly world-class offering, ensuring the UK remains at the forefront of the manufacture and delivery of vaccines and advanced therapies. Moreover, it will further strengthen and leverage the rapidly-growing health and life science sector in Birmingham and the Midlands.”

The National Training Centres are a part of the ATSTN initiative, which also includes an online training platform to provide remote learning for those currently working in the vaccine manufacturing and advanced therapy industry, and a ‘career converter’, which maps an individual’s transferrable skills from adjacent sectors into recommended roles for this industry.

The ATSTN, driven by industry and coordinated by the Cell and Gene Therapy Catapult (CGT Catapult), was launched in December 2020 with £4.7m in funding awarded from BEIS. The initiative was designed in collaboration with industry to create opportunities to upskill, through digital and practical on-site courses, current professionals and leverage skills from individuals coming from other sectors.

Matthew Durdy, Chief Executive Officer, Cell and Gene Therapy Catapult, commented: “The UK ATMP industry is expanding rapidly, and to support that tremendous growth the industry needs skilled people. The UK is making one of the biggest commitments anywhere in the world to training in this sector, keeping it as the “go to” place for the cell and gene therapy industry. As part of the ATSTN programme, the University of Birmingham is well placed to develop and deliver high-impact training courses utilising its world leading delivery technologies”.

Sponsored by the Department for Business, Energy & Industrial Strategy (BEIS), ATSTN’s national training centres includes RoslinCT with its academic partners and the National Horizons Centre.

a mother and daughter select healthy foods from a selection of fruits and grains

Increased risk of chronic kidney disease in people with ‘healthy’ obesity

Written by Louise Stanley on 21/06/2021. Posted in Inflammation and chronic disease.

People with ‘healthy’ obesity have a 66% increased risk of chronic kidney disease compared to metabolically healthy individuals with normal weight, finds a new study led by the University of Birmingham.

Those that are metabolically healthy (do not suffer with metabolic conditions such as hypertension, diabetes, high cholesterol or cardiovascular disease) and are overweight but do not have obesity are at a 30% risk of chronic kidney disease compared to healthy people with normal weight, the study found.

The research also found that the increased risk was greater in those aged under 65, while also the more the number of the metabolic complications a person has the higher risk of chronic kidney disease even in the normal weight range.

The research, published in the American Journal of Kidney Disease, was carried out in collaboration with University Hospitals Birmingham NHS Foundation Trust and the University of Warwick.

The retrospective population-based cohort study examined the GP records of around 4.5 million individuals from the UK and tracked their health over an average of almost five-and-a-half-years. Of the 4.5 million individuals, 1,040,921 (23.4%) and 588,909 (13.2%) were metabolically healthy overweight and metabolically healthy obese, respectively.

Chronic kidney disease has a major impact on global health and cost the UK National Health Service £1.45 billion in 2009-2010. In 2017, 697.5 million people in the world had the disease, and it accounted for 1.2 million deaths. The prevalence of chronic kidney disease increased by almost 30% between 1990 and 2017, while the number of deaths caused by the condition rose by 41.5% in the same period. Similarly, the prevalence of obesity is also on the rise, tripling between 1975 and 2016.

First author Dr Jingya Wang, Research Fellow at the University of Birmingham, said: “Our results demonstrate that individuals with metabolically healthy obesity might have a higher risk of developing chronic kidney disease compared with normal weight individuals, especially those younger than 65 years.

“Looking to the future, a clinical trial of a weight loss intervention could be considered in these individuals to help us establish whether this can reduce their high risk of chronic kidney disease.”

Dr Abd Tahrani, Senior Lecturer in Metabolic Endocrinology and Obesity Medicine at the University of Birmingham, says: “It is likely that weight loss in people with metabolically healthy obesity is likely to reduce their risk of chronic kidney disease as it will also reduce their risk of future type 2 diabetes, and hypertension, both of which can worsen kidney function and result in chronic kidney disease, however this needs to be examined in future trials.

“In addition, we know from previous trials that weight loss in individuals with normal weight can reverse non-alcoholic fatty liver disease for example, hence weight loss could offer an important strategy to prevent obesity complications in this population.”

Dr Krish Nirantharakumar, also of the University of Birmingham, said: “Furthermore, our results suggest that individuals with normal weight who have metabolic abnormalities are also at a higher risk of chronic kidney disease and as such might benefit from meticulous metabolic control to reduce the risk of developing the condition.

“Ultimately, chronic kidney disease is largely preventable, and therefore, it is important to identify and treat the underlying modifiable causes and risk factors.”

This new study follows previous research led by the University of Birmingham and published in 2017 in the Journal of the American College of Cardiology which showed that individuals living with obesity who are metabolically healthy have an increased risk of cardiovascular disease events compared to those who are normal weight without metabolic abnormalities.

Neil Thomas, Professor in Epidemiology and Research Methods at the University of Birmingham, adds: “This new study and our previously published study together demonstrate that individuals who are metabolically healthy can develop organ damage over time.

“Therefore, metabolically healthy obesity should not be considered ‘benign’ or harmless and addressing obesity in metabolically health people might reduce organ damage including chronic kidney disease.”

Young patients with cancer to benefit from £1million investment in genomic testing

Written by Louise Stanley on 11/06/2021. Posted in Cancer outcomes, Early diagnosis and detection, Experimental medicine.

Children and young people living with cancer from across the West Midlands, Oxfordshire and parts of Southern England will now benefit from improved genetic testing, thanks to a seven-figure donation to Birmingham Children’s Hospital Charity from Children with Cancer UK, in partnership with Kwik-Fit.

Home to one of the largest children’s cancer centres in the UK, BHP member Birmingham Children’s Hospital cares for over 200 patients with cancer, leukaemia and brain tumours every year, from the West Midlands and beyond.

Genomic testing for patients diagnosed with cancer is incredibly important and over the last decade, large scale sequencing projects have identified pertinent DNA changes, which have enabled scientists to develop new and improved cancer drugs and treatments to specifically target these variations.

Sequencing all possible DNA changes in a single test gives scientists the best possible chance of detecting the genetic changes driving a child’s cancer; and knowing the genetic makeup of a child or young person’s cancer, or tumour, allows clinicians to offer a more tailored treatment.

Targeted therapies have improved the number and different types of treatment offered to children and young people, aimed at saving more lives and improving the quality of life for patients living with cancer.

The UK’s largest genetics laboratory, the West Midlands Regional Genetics Laboratory, based at BHP member Birmingham Women’s and Children’s NHS Foundation Trust, provides cancer genetic services for patients across the West Midlands, Oxfordshire and parts of Southern England, covering a population of 12million.

Now a donation of just over £1million to Birmingham Children’s Hospital Charity has allowed the laboratory to purchase a high-throughput next generation sequencing platform. This investment is possible thanks to the incredible fundraising efforts of Kwik-Fit’s staff, customers and suppliers who raised the substantial sum after Kwik-Fit employees chose Children with Cancer UK as the company’s national charity partner.

The NovaSeq 6000 is a state-of-the-art piece of DNA sequencing equipment which has enabled the rapid expansion of cancer genetic testing at the West Midlands Regional Genetics Laboratory.

Initial forecasts provided by NHS England and NHS Trusts across the West Midlands, Oxfordshire and parts of Southern England suggest that approximately 560 children and young people per year could benefit from large cancer panel genetic testing following the installation of the NovaSeq.

The significant gift also allowed for the refurbishment of the laboratory in which the NovaSeq will sit.

The Chairman of Birmingham Women’s and Children’s NHS Foundation Trust and its Charity, Professor Sir Bruce Keogh, former Medical Director of the NHS in England, said: “The NovaSeq 6000 has dramatically enhanced our ability to identify diagnostic and prognostic biomarkers for childhood and young people’s cancers, thereby enabling our expert scientists and doctors to quickly optimise and develop more effective and less toxic treatments for children and young people with cancer.

“We’re incredibly thankful to Children with Cancer UK and all the employees at Kwik-Fit for enabling us to expand our cancer genetic testing capability in this way. It really will make a difference to thousands of families living with a cancer diagnosis.”

Children with Cancer UK, the charity dedicated to the fight against childhood cancer, is a long-term supporter of Birmingham Children’s Hospital and is making its second £1million donation to the hospital’s charity. The first helped ensure the opening of a brand new Children’s Cancer Centre in 2018.

Children with Cancer UK Trustee, Nick Goulden, said: “We are delighted the new NovaSeq 6000 has been installed at the West Midlands Regional Genetics Laboratory, ready to serve its young cancer patients across the region. By offering personalised treatments through genetic sequencing, it’s another step towards our ultimate goal of saving the life of every child and young person diagnosed with cancer.

“We are also incredibly grateful for our year-long partnership with Kwik-Fit who shared this vision with us. Through their innovative and dedicated fundraising, Kwik-Fit employees raised £1million to make all of this possible and the legacy of our relationship will benefit the lives of thousands of children and young people in the future.“

Kwik-Fit’s partnership with Children with Cancer UK, which took place before the pandemic, saw its staff participate in events such as the Virgin Money London Marathon and the Simplyhealth Great North Run. It also organised various fundraising activities including bake sales, static bike challenges, car washes and sponsored walks. In addition, staff swapped cars for cycles as part of the company’s first-ever ‘Tour De Branch’ – a nationwide bike ride in which over 80 employees covered 2,500 miles between 120 Kwik-Fit centres.

Mark Slade, managing director of Kwik-Fit, said: “We were delighted to hit our fundraising target of £1million which has enabled Birmingham Children’s Hospital Charity to invest in such an important piece of equipment.

“I would like to congratulate and thank all of the Kwik-Fit staff for their tremendous effort and dedication and all our customers and partners who supported us – we would not have been able to achieve this target without them. We hope that this vital testing equipment will make a massive difference to the outcome for many families in the future.”

Better treatment for miscarriage patients is also more cost effective

Written by Louise Stanley on 13/05/2021. Posted in Clinical trials, Maternal health.

A new drug combination that is better at treating miscarriage is also more cost effective than current standard NHS treatment, finds a new study led by BHP founder-member the University of Birmingham and Tommy’s National Centre for Miscarriage Research.

A previous study by the same team and published in The Lancet in August last year, found that a combined drug treatment is more effective than the standard medication for women having miscarriages without symptoms – also known as missed, delayed or silent miscarriage.

Missed miscarriage occurs when a baby has died in the womb but the mother hasn’t had symptoms, such as bleeding or pain. Current hospital restrictions on surgery mean that many women face waiting for the miscarriage to happen by itself, which can take weeks and still might not happen, or being offered medication to speed the process along.

National guidelines recommend a treatment called misoprostol, which is successful in most cases – but some women wait anxiously for weeks, repeating the medication and eventually needing surgery.

The research published in The Lancet in August 2020 showed that misoprostol is more effective when combined with mifepristone, an anti-progesterone drug used to induce labour. The trial found that the combined drug treatment worked in 83% of cases, compared to 76% in the misoprostol and placebo group – and crucially, it reduced the need for surgery. One in four women (25%) given the placebo later needed an operation to complete the miscarriage, compared with less than one in five (18%) of those who had the new medication.

Now the team has carried out a further study to assess the cost-effectiveness of mifepristone and misoprostol combined compared with misoprostol alone for the medical management of a missed miscarriage.

The National Institute for Health Research (NIHR) funded study involved 711 women across 28 UK hospitals with a diagnosis of missed miscarriage in the first 14 weeks of pregnancy, who were randomly assigned to receive either mifepristone or a placebo drug followed by misoprostol two days later.

Published in the British Journal of Obstetrics and Gynaecology, the study found the new combined drug treatment was on average £182 cheaper for each successfully managed miscarriage than the current standard NHS medication.

As this is the largest ever study into the most effective medical treatment for missed miscarriage, and the results are so clear, researchers and campaigners are calling for guidance from the National Institute for Health and Care Excellence (NICE) to be updated in light of the newly published findings. In the meantime, Tommy’s experts encourage anyone diagnosed with missed miscarriage to ask their doctor about the combined drug treatment.

Senior author Tracy Roberts, Professor of Health Economics at the University of Birmingham, said: “Pregnancy loss causes heartbreak for millions of families, and it is crucial that we find better ways to care for everyone going through miscarriage. Our findings could have huge benefits if they’re translated into clinical practice, with better outcomes for patients and lower costs for care services.”

First author Dr Duby Okeke Ogwulu, of the University of Birmingham’s Institute of Applied Health Research, added: “We hope the NICE guidance will be updated in light of this new evidence, so that everyone who needs it has access to the most effective treatment.”

Tommy’s CEO Jane Brewin commented: “Besides the physical harm, miscarriage can have serious psychological consequences, which can be made worse by the trauma of a failed treatment forcing mothers to endure weeks of carrying a baby they know has died.

“One in four pregnancies ends in loss, and while our researchers work to understand how we can prevent this, it’s vital their latest findings are put into practice so that everyone going through miscarriage has the best possible care. Particularly given Covid-19 pressures on the NHS, our new study could be applied to make better use of precious resources, as well as reducing the toll miscarriage can take on parents.”

An estimated 23 million miscarriages occur every year worldwide – equating to 44 pregnancy losses each minute. Miscarriage (defined as the loss of a pregnancy before 24 weeks) costs the UK at least £471 million a year, through direct impact on health services and lost productivity, but scientists expect the costs surpass £1 billion a year when factoring in longer-term physical and mental health impacts.

Claire Bromley, aged 32, from Sittingbourne in Kent, chose surgery when she had a miscarriage last year, as her previous experience when medication failed was so distressing.

Claire said: “The whole process took around 3 months and was extremely traumatic, so I hope this new drug will mean others don’t have to suffer like I did. I was told medication would take a few hours to work, but started bleeding and cramping in minutes, while stuck in hospital waiting for other prescriptions. Despite taking effect so fast, the medication didn’t work, so I was sent for surgery – and when that failed too, I had to take the pills again. With my second miscarriage, I chose surgery right away to avoid the risk of repeating such a long and painful treatment.”

Katy Allan, aged 43, from South Yorkshire has experienced multiple miscarriages and a range of treatment, initially having surgery that caused internal scarring and later choosing medication in the hope it would cause less damage.

Katy said: “The treatment for my third miscarriage was a four-month long nightmare, with several rounds of medication and hospital staff trying to physically remove the pregnancy while I was awake, ending in painful surgery; it was one of the most horrendous experiences of my life and I remain completely traumatised. I couldn’t move on physically or mentally because I was pregnant and not pregnant for months, with tests remaining positive and hormones still racing long after we heard those spine-shivering words of ‘I am so sorry but there is no heartbeat’. The long ordeal of treatment made miscarriage even harder so I hope this new research can help to prevent others from going through what I did.”