Month: April 2022

New spinout Healome Therapeutics to speed development for eye therapeutics

Written by Louise Stanley on 27/04/2022. Posted in Experimental medicine.

BHP founder-member the University of Birmingham has created a new spinout, Healome Therapeutics Ltd, to commercially deploy a platform that delivers a ‘pro-healing’ microenvironment for the leading causes of preventable blindness.

The company’s leading application will be in ocular surface diseases, which are notoriously challenging conditions to treat, and have progressively larger impacts on quality of life as the diseases run their course.

The Healome technology is a novel fluid-gel material that flows like a liquid, and self-structures into a thin, clear, protective layer over the surface of the eye which is gradually dispersed and cleared away by blinking over 2-8 hours (customisable depending on application).

The gel can be used alone, or as a ‘carrier molecule’ to deliver other therapeutics.

Studies have already shown that one of Healome’s formulations has anti-fibrotic (anti-scarring) activity and these healing properties are augmented by combining it with other therapeutics.

The technology was developed by a team led by Professor Liam Grover who is Director of the University’s Healthcare Technologies Institute (HTI). It is envisaged that treatments developed from this platform will come in the form of clear degradable ‘ocular bandages’ that can be applied like normal eye drops.

Professor Grover, who is also a co-founder of Healome Therapeutics, commented: “There are many cutting edge drugs on the market or in development for diseases that affect the surface of the eye. One of the biggest challenges is to keep therapeutics on the surface of the eye for sufficient time for them to have an effect and more generally to regain or replace all the functions of the tear film.”

The company’s founding directors already have prior experience in commercialisation and advancing therapies towards Phase I-III clinical trials and include Professor Anthony Metcalfe, Industrial Professor of Wound Healing, formulation engineer Dr Richard Moakes, and Dr Richard Williams, whose work at the HTI involves translating healthcare technology concepts to finished products ready to enter clinical trials.

Although Healome will initially concentrate on Dry Eye Disease, in the long-term the company aims to partner with healthcare companies to co-develop new therapeutics for delivery to the surface of the eye.

The gels respond to shear stress, which allows it to change back and forth from a liquid to a soft-solid consistency according to the physical forces applied to it, such as extrusion from a container, or blinking.

Its mechanical and drug diffusion properties can be ‘tuned’ by physical rather than chemical changes to the base polymers. These attributes mean that pre-clinical or early clinical safety studies for new formulations will not need to be repeated and will reduce the time and cost to bring new products to market.

CEO of Healome, Dr Richard Williams, commented: “Ocular surface diseases leading to Dry Eye have a disproportionately large impact on health, well-being and the ability to enjoy life. These conditions can also be very expensive for patients to manage. There are many unmet patient, clinical and industrial needs in this area, which Healome Therapeutics is well-placed to address. Pre-clinical safety of the platform is well-established, GMP manufacturing has been set up to supply planned phase 1 trials and we have brought in significant executive experience in eye care to accelerate plans.”

The researchers behind Healome have already raised £2.8m grant funding from the Medical Research Council (MRC) to progress the original concept from lab bench to completing phase 1 human trials. The developed platform and supply chain was then applied to help tackle challenges in ocular surface diseases via a £1.3m grant from the National Institute of Health and Care Research (NIHR) Invention for Innovation programme. The platform has also shown early promise in dermal and orthopaedic applications.

Healome Therapeutics has already raised £400k funding from Innovate UK and SFC Capital, and is now establishing its own laboratories at the Birmingham Research Park, which has been nurturing high-growth biomedical companies since 1986.

Phase I human trials to test the core technology in combination with therapeutics known to prevent corneal scarring and manage severe dry eye will commence in Q2 2022, supported by the University of Birmingham GMP manufacturing facility.

Urine test for bladder cancer could replace thousands of invasive procedures each year

Written by Louise Stanley on 25/04/2022. Posted in Cancer outcomes, Clinical trials, Early diagnosis and detection.

Birmingham researchers funded by Cancer Research UK and liquid biopsy company Nonacus have developed a new urine test for bladder cancer, which could reduce the need for invasive and time-consuming procedures to diagnose the disease.

The test will use highly sensitive liquid biopsy technology developed by Nonacus in conjunction with a panel of biomarkers developed and validated by Mr Rik Bryan and Dr Douglas Ward from the Bladder Cancer Research Centre at BHP founder-member the University of Birmingham, to detect the presence of bladder cancer by finding DNA from tumour cells present in the urine.

The biomarker panel, which consists of 443 genetic mutations that are common in bladder cancer has been validated in a deep sequencing study recently published in European Urology Oncology.

In this study, which was funded by Cancer Research UK and the Medical Research Council, the researchers used the test to analyse urine from 165 people with bladder cancer that had experienced haematuria (blood in the urine), and successfully detected the disease in 144 of them (87%).

The researchers also looked at using the test in 293 patients who had already been treated for bladder cancer and were being monitored for the cancer returning. In this setting, the test returned a higher proportion of false positive results compared to when used in the haematuria clinic (37.5% vs 15.2%), with 99 positive urine tests without a tumour being seen by cystoscopy on the same day. However, during their follow up monitoring, the patients who had those positive results had almost 3-times higher (11% vs 4%) rates of the cancer returning within 24 months indicating that the test could help detect recurrent disease before it is visible by cystoscopy (the camera inspection of the bladder). Further research is needed for the test to be used for surveillance.

Lead researcher Mr Richard Bryan said: “Even though cystoscopy is good at detecting bladder cancer, it’s invasive and time consuming for patients, so we need a better way to diagnose patients. In the future our test could be an easier way to get people with bladder cancer diagnosed faster, and could mean that tens of thousands of cystoscopies on healthy patients can be avoided each year.”

Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK said “These findings show that this urine test could help diagnose bladder cancer more easily. Early detection of cancer is key for improving patient outcomes and research like this could help identify the patients that need treatment soonest, while easing the pressures of diagnostic procedures on the NHS. We look forward to seeing how the test performs in the next clinical trial.”

The researchers are working in partnership with Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, to turn their approach into a clinical test for patients to be used within the NHS, and will start a clinical study funded by Cancer Research UK and involving over 3000 patients to evaluate just how powerful the test is at reducing the number of cystoscopies.

Each year, over 300,000 cystoscopies are carried out in England, however, around 80% of patients with haematuria who’ve had cystoscopy are found to have no cancers or abnormalities^1,2. The researchers believe that using the urine test in haematuria clinic could reduce the number of patients requiring a cystoscopy by at least 45%.

Civilians and military take part in study to improve concussion prognosis

Written by Louise Stanley on 08/04/2022. Posted in Clinical trials.

A major UK study to identify new ways to accurately predict if patients will develop long-term complications as a consequence of concussion has been launched, led by experts at BHP founder-member the University of Birmingham and the Defence Medical Rehabilitation Centre, in collaboration with the Defence Medical Services.

With year one funded by the Ministry of Defence (£2m) and projected to run over eight years, the multi-faceted study will include a trial involving 400 civilians and 400 military personnel aged over 18 with a new diagnosis of concussion (also known as a mild traumatic brain injury or mTBI) which has resulted in them needing hospital treatment or rehabilitation.

At specific time intervals over two years, the participants will take part in nine different areas of research using a variety of medical techniques and assessments to establish if these can be used routinely by medics as ‘biomarkers’ to indicate prognosis and long term impact of concussion. Medical techniques and assessments being trialled include brain imaging and function, analysis of blood and saliva samples, and headache measures, as well as mental health, vision, balance, and cognitive performance.

mTBI is common and has been declared a major global public health problem, with 1.4 million hospital visits due to head injury annually in England and Wales – 85% of which are classified as mTBI. It is also estimated that up to 9.5% of UK military personnel with a combat role are diagnosed with mTBI annually.

The research will involve 20 University of Birmingham experts working across disciplines, including neurology, psychology, sports medicine, mathematics and academics within the University’s Centre for Human Brain Health, and will be coordinated by Birmingham Clinical Trials Unit. It will also be driven by experts at the Defence Medical Rehabilitation Centre Stanford Hall; Aston University, Imperial College London; University of Westminster; University of Nottingham; Royal Centre for Defence Medicine; and University Hospitals Coventry & Warwickshire.

Alex Sinclair, Professor of Neurology at the University of Birmingham and Chief Investigator of the project, called mTBI-Predict, explained: “Although classified as mild, and many recover, the consequences of concussion can be profound with many patients suffering long-term disability due to persistent headaches, fatigue, imbalance, memory disturbance, and poor mental health including post-traumatic stress disorder, while it can have a significant impact on the economy through loss of working hours and demand on the health system.

“Identifying those patients most at risk of these disabling consequences is not currently possible. There is therefore a pressing need to develop accurate, reproducible biomarkers of mTBI that are practical for use in a clinical setting and can predict long-term complications. Our programme of research will deliver a step change in the care of patients with mTBI, enabling a personalised medicine approach to target early intervention for those most in need but also identifying those with a good prognosis who can return rapidly to activities of daily living.”

Co-Chief Investigator, Air Vice-Marshall Rich Withnall QHS Director of Defence Healthcare, UK Ministry of Defence said: “I am delighted that the Defence Medical Services, including the Defence Medical Rehabilitation Centre at Stanford Hall, will be working hand-in-glove with class-leading civilian colleagues and the National Rehabilitation Centre Programme. I fully support this ground-breaking research which I am confident will lead to significant clinical innovation to benefit military and civilian patients, and have translational positive impact for sporting activities from grass-roots to elite levels.”

Peter McCabe, Chief Executive of Headway – the brain injury association, said: “We know that even a seemingly minor head injury can have a major impact on a person’s life – and often the lives of those closest to them. This is particularly the case if the brain injury goes undiagnosed or its effects are mistaken for other conditions. The frustration of not having an accurate diagnosis or receiving the right support can be compounded by the lack of a clear recovery pathway or timeline. We therefore welcome this study in the hope that it can advance our understanding of concussion and mTBI.”

Genetically-determined levels of inflammation linked to neuropsychiatric illness

Written by Louise Stanley on 04/04/2022. Posted in Inflammation and chronic disease, Mental health.

A potential link between inflammation and the structure of specific regions of the brain has been identified by researchers at BHP founder-members the University of Birmingham.

The study, published today in JAMA Psychiatry, may be particularly relevant for neurodevelopmental psychiatric disorders including autism spectrum and schizophrenia.

Researchers say the findings could open up a completely new target for the pharmacological treatment of these disorders, which has not significantly changed since the identification of antipsychotic medications in the mid-late 20th century.

The research was carried out by a team based in the University’s Institute for Mental Health and Institute and Institute of Cancer and Genomic Sciences, with collaborators from the University of Cambridge, Manchester and Bristol. It showed that genes associated with inflammation, particularly interleukin (IL) 6, are linked to a reduction in grey matter volume in certain areas of the brain known to be implicated in neuropsychiatric disorders.

Using records from the UK Biobank, a large-scale biomedical database, the team was able to compare genetic variants which affect levels of IL-6, and other inflammatory genes in more than 20,000 patients with changes in grey matter volume in specific areas of the brain.

They were able to show strong links between IL-6 and brain structure particularly in the temporal and frontal regions. Further analysis using the Allen Human Brain Atlas, showed that genes overexpressed in these areas are associated with conditions such as epilepsy, cognitive dysfunction, and schizophrenia.

Professor Rachel Upthegrove of the University of Birmingham Institute for Mental Health, explained: “This study shows that the IL-6 gene, which we know to be linked to systemic inflammation, also affects brain structure in areas associated with these neuropsychiatric disorders. Understanding these links offers an exciting opportunity to explore new treatments which target IL-6. This could be the first new target for severe mental illnesses including schizophrenia identified in more than 60 years.”

Dr John Williams, of the Institute for Cancer and Genomic Sciences at the University, a first author on the paper, said: “Current treatments for these illnesses act on dopamine, a chemical messenger in the brain associated with mood and attention. These drugs can have side effects, however, and they are not effective in all patients.

“There are drugs already on the market which target inflammation as well as the opportunity to screen potential new compounds. Finding a new avenue for exploring the links between inflammation, brain structure and neuropsychiatric disorders is really exciting.”

The work is part of the PIMS (Psychosis Immune Mechanism Stratified Medicine Study) programme, led by the University of Birmingham and set up to investigate the links between inflammation and psychosis. In the next phase of the research, the group will carry out experimental studies to knock out IL-6, as well as replicating the Biobank research in more diverse patient cohorts.