Case Studies

Birmingham Life Sciences Park will offer our partners direct access to academic, scientific and clinical facilities and expertise through the Birmingham Health Partners network (partners are the University of Birmingham, University Hospitals Birmingham, Birmingham Women’s and Children’s, which are all in close proximity to the park). 

Below are a few case studies that demonstrate how our unique infrastructure, co-located expertise and embedded partnership working has allowed the rapid development of scientific and medical innovation into improved patient care. 

If you’d like to become part of this pioneering development, work with us, or find out more about how Birmingham Life Sciences Park could benefit you, please contact us at blsp@contacts.bham.ac.uk

Cutting-edge portable genomic sequencing to track infectious diseases

Academic innovation can create opportunities to modify and deploy industry innovation in new environments in order to tackle new challenges. A great example of this is our work with Oxford Nanopore and their MinION portable genome sequencer.

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What: A portable genomic sequencing device

Why: Conventional sequencing technologies are difficult to deploy in developing countries, particularly when continuous power can be unavailable

How: We used Oxford Nanopore’s MinION technology to track the recent Ebola crisis in West Africa and provide real-time sequencing results 

Conventional sequencing technologies are difficult to deploy in developing countries where availability of continuous power and cold chains, laboratory space, and trained personnel is restricted. In addition, some genome sequencer instruments, such as those using optical readings (e.g. the Illumina platform), require precise microscope alignment and repeated calibration by trained engineers.

Birmingham has a strong track record of expertise in the use of cutting-edge genomics and metagenomics approaches to the diagnosis, treatment and surveillance of infectious disease, and more recent work on development of novel sequencing and bioinformatics methods to aid the interpretation of genome and metagenome scale data generated in clinical and public health microbiology – particularly highlighted by the work of Professor Nick Loman within the Institute of Microbiology and Infection.

While the market-leading MinION technology had previously been utilised in investigations of a bacterial outbreak, the Loman lab set out to use it in the context of a viral outbreak setting, specifically the recent Ebola crisis in West Africa. The team designed a laboratory protocol to permit EBOV genome sequencing on the MinION in order to isolate sufficient DNA for sequencing, and demonstrated proof of principle in pilot experiments at the Defence Science and Technology Laboratory (DSTL) Porton Down, before designing a portable genome surveillance system – in effect a ‘mobile lab’ built around the technology – that could be transported to West Africa.

Here, academic and inter-sector networks played a key role in demonstrating utility and ensuring the reach and impact of the technology. After deployment of the genome surveillance system, they worked in partnership with diagnostic laboratories in Guinea to provide real-time sequencing results to National Coordination in Guinea and the World Health Organisation (WHO).

Collaborating laboratories provided leftover diagnostic RNA extracts for sequencing. The genome sequencing workflow, including amplification, sequence library preparation and sequencing could be accomplished within one working day. In one case, including remote bioinformatics analysis, the fastest time from patient sample to result was achieved in less than 24 hours, although the protocol was usually performed over two working days. In half of cases, they were able to generate sufficient reads on the MinION (between around 5,000 and 10,000) in less than an hour.

Professor Nick Loman

Professor Nick Loman

Professor of Microbial Genomics and Bioinformatics

“"Until even just a year ago, it would have been impractically difficult to sequence a whole human genome, but thanks to recent advances and innovations such as nanopore technology we now have the ability to sequence very long fragments of the genome"”

 

This work, published in Nature and repeated later during the Zika outbreak in Brazil, conclusively demonstrated for the first time that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.

Real-time genomic surveillance is now a new tool in the international arsenal to assist difficult epidemiological investigations, and to provide an international and environmental context to emerging infectious diseases. The work of the Loman lab in partnership with Oxford Nanopore has now improved and validated the real-world utility of their new technology. This should help improve the efficiency of resource allocation and the timeliness of epidemiological investigations through genomically-informed investigations of transmission chains, also increasing the possibility of identifying previously unknown chains of transmission.

Precision medicine clinical trials at scale and pace

The patient, clinical and academic environment in Birmingham provides a unique environment for design and delivery of clinical trials, as exemplified by National Lung Matrix – the largest precision medicine clinical trial in cancer in the world.

What: The world’s largest precision medicine clinical trial in cancer

Why: Designing and delivering effective clinical trials to validate new therapies is proving increasingly challenging in terms of cost, scale and pace

How: The patient, clinical and academic environment in Birmingham provides a unique environment for design and delivery of clinical trials

Precision medicine is revolutionising treatment opportunities, but designing and delivering effective clinical trials – in terms of cost, scale and pace – to validate new therapies is proving increasingly challenging in the context of genomic variation and the avalanche of new drugs.

Birmingham hosts the largest Cancer Research UK Clinical Trials Unit (CRCTU) in the UK – part of one of the largest clusters of trials expertise in Europe – with significant expertise in early phase trials and complex methodology. Supported by a range of strong NHS partnerships providing access to a diverse population (ethnically, socio-economically and culturally) with a high prevalence of cancer, and significant expertise in genetic/genomic testing, digital curation and patient stratification, we have an unrivalled testbed for new therapies. This is complemented by the West Midlands Genomic Medicine Centre and Regional Genetics Laboratory – both led by Birmingham Health Partners, and both the largest of their kind in the UK.

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Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, caused by a range of specific mutations varying between individuals – hence the need for a precision medicine approach in testing new therapies. The National Lung Matrix Trial is a precision medicine trialof national and international strategic importance that links in with the second phase of Cancer Research UK’s stratified medicine programme (SMP2).

The trial is a phase II non-randomised umbrella design initially evaluating seven targeted drugs in 20 different biomarker-defined cohorts and including an additional cohort for patients with no actionable targets. The trial opened to recruitment March 2015 and in June 2016, we received CRUK funding to extend the trial for a further 2 years to support the inclusion of 2 new trial arms. The complexity of the trial required a novel statistical approach and a Bayesian adaptive design has been adopted. Implementation has required the team at CRCTU to have an understanding of the complex biology underpinning the trial. Eligible patients are recruited to treatment arms depending on molecular targets identified by the CRUK Stratified Medicine Programme 2 (SMP2).

The trial recruits from the 18 Experimental Cancer Medicine Centres (ECMCs) across the UK – again, Birmingham has one of the largest ECMCs nationally supporting a range of studies and clinical connectivity – with each treating additional patients referred from feeder sites. Target recruitment for each drug-biomarker cohort is 30 patients to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation with interim analyses after 15 patients. Recruitment relies on the joined-up ability between our NHS partners and our trials teams to convert patients with advanced NSCLC from SMP2 into the Matrix trial, and the trial has successfully recruited almost 150 patients with some cohorts now reaching their formal planned interim analysis.

The success of the trial has showcased our ability to work closely with multiple industry partners – with current partners offering new compounds and new partners joining the collaboration – as well as the SMP2 team at CRUK and a large Trial Management Group including 20 national leading experts. New trial methodologies – including adaptive designs, basket and umbrella trials – are increasingly of interest to the pharmaceutical industry and SMEs as they offer efficiencies and speed, which can otherwise lead to significant cash burn in therapy development. In terms of acceleration, the critical link between academic insight into methodology and sustainable, well-managed trial delivery, linked with the power of the NHS to access and stratify the appropriate populations – all of course boosted by our physical co-location –  means that Birmingham has a nationally-leading ability to present a unified ‘front door’ for trials development and delivery.

Innovative medical technology development and testing

The ability to connect specific clinical challenges with focused academic innovation can be critical to the development of products that will deliver tangible patient impact. This is particularly true for medical devices, as with our revolutionary eye-drop to prevent corneal scarring and blindness.

eye dropperWhat: Revolutionary eye-drop to prevent corneal scarring and blindness

Why: Injuries to the surface of the eye are a leading cause of visual loss, but there are few therapeutic options to modify, minimise or reverse scarring

How: Birmingham hosts the largest medical device cluster in the UK with an impressive and extensive infrastructure in addition to world class hospital trusts

 

Injuries to the surface of the eye as a result of burns, infections, inflammation, trauma and surgery, can cause corneal scarring and opacity – a leading cause of visual loss. There are few therapeutic options to modify, minimise or reverse scarring to maintain corneal transparency and visual function, and these are not always effective. With a global prevalence of 5.1%, the incidence of visual loss is ~8 million people/year and costs ~£150 billion/year, and the WHO has consequently made this a priority area programme to prevent world-wide blindness.

Birmingham hosts the largest medical device cluster in the UK with an impressive and extensive infrastructure in addition to world class hospital trusts, including the Institute for Translational Medicine and the new Medical Device Testing and Evaluation Centre (MD-TEC) linked to our Healthcare Technology Research Institute. Co-located with a host of clinical/academic centres of excellence focused on translational challenges – such as the NIHR Surgical Reconstruction and Microbiology Research Centre (SRMRC) – this provides academics, clinicians and industry with a perfect environment to rapidly mature their nascent technologies, provide training opportunities, and act as an integrated coordination point to bring multi-disciplinary teams together around shared challenges and opportunities.

In this case, bringing together neurosciences and ophthalmology expertise with Professor Liam Grover’s healthcare technologies team led to the discovery that combining decorin and collagen results in enhanced anti-scarring bioactivities, creating a microenvironment that enables anti-fibrotic and anti-inflammatory factors to promote scarless wound healing and improve clinician and/or patient-reported visual outcomes. The combination of academic, clinical and technological expertise we were able to bring together rapidly pushed this along a translational escalator – securing over £5million through internal and external funding schemes from MRC, Wellcome Trust and NIHR to accelerate development of a synthetic, transparent, anti-scarring eye drop for the management of patients at risk of corneal scarring.

eye drop dispensed imageIn 2018 we will lead the first in-human clinical trial to assess the treatment’s safety and efficacy in patients with microbial keratitis. This will create a unique collaboration between the University of Birmingham, Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust and the Queen Elizabeth Hospital Birmingham. The clinical trial will also help move the technology along the translational pathway towards regulatory approvals and commercial realisation. The research team has already consulted with patients, practitioners and regulatory bodies, and potential commercial partners have also registered their interest in the technology.

The anti-scarring eye drop will not only have significant positive impacts for patients, but also socio-economic impacts – patients with ocular damage will carry a reduced direct and indirect cost of treatment burden as the eye drop may be self-administered in a home and/or community setting, negating the need for prolonged hospitalisation and clinic attendance. In the not too distant future, patients will be able to access this revolutionary sight-saving eye drop to prevent the devastating consequences of corneal damage.