BioScience Today 18

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ISSUE18

Drug delivery

Biosimilars set to make significant UK impact patient recruitment • dermatology • biosimilars • life sciences • diagnostic devices • intellectual property • optometry

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Welcome Increasing access Ellen Rossiter Editor in chief

Editor Ellen Rossiter ellen.rossiter@distinctivepublishing.co.uk

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What are the greatest challenges facing healthcare?

Increasing access to treatment may well be one and it’s a concern at the heart of several articles in this issue. News broke recently that the NHS has saved more than £700 million from the annual medicines bill through the use of ‘generic’ and best value ‘biologic’ treatments. In this edition of Bioscience Today, we learn more about the role of biosimilars in widening patient access.

Making it possible for more people to participate in clinical trials is also at the heart of efforts to increase accessibility. The National Institute for Health Research (NIHR) has worked to improve recruitment to clinical trials over the last decade and last year saw record levels of participation with over 870,000 people taking part in clinical research. Progress may be good, but the NIHR Clinical Research Network (CRN) is focusing on improving access still further. We take a look at their efforts to bring patients and life-sciences’ researchers together.

A clinical trial supported by the NIHR CRN South London is breaking down barriers to participation by taking the project to people.

Step into the ATTIC bus and you’ll find a multidisciplinary team working to treat homeless people with Hepatitis C. Rethinking the traditional model of outpatient care, the ATTIC team broaden access by treating patients in the community, overcoming barriers which may exist to patients attending multiple hospital appointments. Discover more about their work as you turn the pages of this issue.

If you were asked to name a diagnostic procedure which has changed little since its introduction, what would you say? You might come up with the colonoscopy. Introduced in the late 1950s, the colonoscope has remained much the same over the intervening decades.

An extremely skilled procedure which has a crucial role in diagnosing colon cancer early, over one million people are referred for colonoscopies each year.

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Colonoscopies, however, are also invasive procedures which can be painful and around one in ten fail to be completed, which is why work is afoot to transform the device. We learn about a project which is working to make colonoscopies painless and easier to carry out, changing the patient experience for the better and potentially reducing NHS waiting lists too. Find out about the tiny robotic capsule which is playing a part in bringing about this transformation.

Blink an eye and you are demonstrating one of the body’s great defence mechanisms – it may seem a straightforward action but it’s one which has many benefits for eye health. Blink exercises are thought to reduce the effects of Dry Eye Disease, for example. In this issue, we learn about the research work ongoing to define and treat a condition which affects hundreds of millions of people around the world. Find out why sometimes it’s the simplest things which work best…

One press release which popped into the Bioscience Today inbox made intriguing and slightly uncomfortable reading for a certain (left-handed) editor. Led by researchers at the University of Oxford, funded by the Medical Research Council and Wellcome, the study identified regions of the genome associated with left-handedness. Leaving the aforementioned editor simultaneously wishing she’d been involved in the research and feeling slightly appalled at the same time.

Why, why, why, do we still feel the need to explain difference? Have we not yet learnt why we shouldn’t be making sweeping statements about any group of people? When these statements relate the characteristics of the aforementioned group to genetics isn’t it even worse? I’ll leave you to read about the research and make up your mind…

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Biosimilars set to make significant UK impact

features

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20 Treading the path less travelled – a different approach to patient recruitment. We hear about a trial engaging homeless people in research.

A British Skin Foundation funded project into atopic eczema

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contents / www.biosciencetoday.co.uk / issue 18 /

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Introduction/Foreword

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Contents

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Biodigestables

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Industry Contributors

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News

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patient recruitment Treading the path less travelled – A different approach to patient recruitment

Patient recruitment: The balancing act

20-23

dermatology A British Skin Foundation funded project into atopic eczema

Many layers to cancer research

24-25

optometry Blinking an eye may seem a simple action, but in this issue, we learn how imperative it is for eye health.

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biosimilars Biosimilars set to make significant UK impact

Moving healthcare forward

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life sciences Whilst the recent past has been one of huge uncertainty with regards to the political and economic landscape across the globe, the past year saw major success in Life Sciences & Healthcare across the Eastern region

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diagnostic devices Diagnostic devices reimagined

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intellectual property Drug delivery encompasses a raft of issues that require real world solutions for the efficacy of drugs to be realised in the cell

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Training and Education The hidden way to fill vacancies, train and retain

26 Blinking an eye may seem a simple action, but in this issue, we learn how imperative it is for eye health

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BIODIGESTABLES

PathAnalyse project Sheffield Teaching Hospitals NHS Foundation Trust has been awarded £67,000 from the Health Foundation’s Advancing Applied Analytics programme to develop innovative new software which could transform NHS outpatient care.

Brain tissue database The UK Brain Banks Network (UKBBN) has enhanced its human brain tissue database. The database now includes searchable genomic data which allows tissue samples to be selected on the basis of genetic risk, as well as clinical and pathological findings.

The enriched database integrates genomic data from over 2,000 brains, which are drawn from collaborating studies, including the Brains for Dementia Research dataset hosted by Dementias Platform UK and a 2016 MRC-funded study by researchers at the University of Cambridge.

Concussion blood test Heart attack prediction Technology developed using artificial intelligence (AI) could identify people at high risk of a fatal heart attack at least 5 years before it strikes, according to new research funded by the British Heart Foundation (BHF).

Researchers at the University of Oxford have developed a new biomarker, or ‘fingerprint’, called the fat radiomic profile (FRP), using machine learning.

The fingerprint detects biological red flags in the perivascular space lining blood vessels which supply blood to the heart. It identifies inflammation, scarring and changes to these blood vessels, which are all pointers to a future heart attack.

A blood test that is currently under development and costs a fraction of the price of a brain scan may flag concussion in CT-negative patients, enabling them to be evaluated for long-term complications. In a study led by UC San Francisco, researchers tracked 450 patients with suspected traumatic brain injury (TBI). The patients, whose injuries were mainly attributed to traffic accidents or falls, all had normal CT scans.

The patients had their blood drawn to measure for glial fibrillary acidic protein, a marker correlating to TBI. The study used a device by Abbott Laboratories called i-STAT™ Alinity™, a handheld portable blood analyser, that produces test results in minutes.

The researchers later confirmed the blood test results against MRI, which offers a more definitive diagnosis of TBI. They found that 120 of these 450 patients (27 percent) had an MRI that was positive for TBI.

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The PathAnalyse project - which will be run in partnership with researchers from the University of Sheffield’s Department of Computer Science and the National Institute for Health Research’s Devices for Dignity MedTech Cooperative - is one of ten being funded in the latest round of the Health Foundation’s Advanced Applied Analytics programme.

BROWN TROUT GENOME Better conservation and management of fish stocks is on the horizon, after the completion of the brown trout reference genome by scientists at the Wellcome Sanger Institute and their collaborators.

The genome will help settle a longstanding debate about whether the physically-varied brown trout is actually a single species or several, and give insights into their ability to quickly adapt to multiple environments.

BioCity Investment announced BioCity has announced investment in precision medicine biotech, Kinomica Ltd., via the Innovate UK Precision Medicine Investment Accelerator.

Spun out from Barts Cancer Institute, Queen Mary University of London, Kinomica Ltd is an early stage precision medicine biotech developing novel technologies for companion diagnostics (CDx) and therapeutic development in precision medicines.

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BIODIGESTABLES

Being Human opens Being Human, the new permanent gallery at Wellcome Collection, has opened its doors exploring what it means to be human in the 21st century.

Divided into four sections, Genetics, Minds & Bodies, Infection, and Environmental Breakdown, the new display presents around 50 artworks and objects. Together, they explore our hopes and fears about new forms of medical knowledge and our changing relationships with ourselves, each other and the world.

Scientists have unravelled the attack initiation mechanism used by so-called ‘predatory bacteria’, which are capable of invading and killing harmful bugs including E. coli or Salmonella.

In a new study, published in Nature Communications, a research team led by the University of Birmingham has investigated the initiation “trigger” from one common type of predator called Bdellovibrio bacteriovorus.

Using a range of techniques, they were able to show how it produces a particular enzyme, called DgcB, when the bacterium encounters potential prey. The enzyme senses modification of its own floppy “tail” and then triggers production of a messenger molecule, switching the bacteria from a cruising and searching mode into invasion mode.

Ebola cases surpass 3000 LifeArc funding LifeArc, a UK-based medical research charity, has announced today it is investing £1.5million into Caldan Therapeutics Limited, a company developing novel therapeutics for the treatment of metabolic diseases based on original work.

Focusing on activators of free fatty acid receptors (GPR120) implicated in the development of non-alcoholic steatohepatitis (NASH), the investment is part of a £2million fund raise to support the optimisation of a lead candidate to progress to later preclinical development. LifeArc is joined in this investment by founding investor Epidarex Capital.

As the Ebola outbreak in the Democratic Republic of the Congo reaches 3000 cases, WHO calls for the full force of all partners to respond and increase their presence in the field to stop Ebola and to address one of the largest and most complex humanitarian crises in the world.

“Our commitment to the people of the Democratic Republic of the Congo is that we will work alongside them to stop the Ebola outbreak,” said WHO DirectorGeneral Dr Tedros Adhanom Ghebreyesus. “Our commitment also means strengthening the health systems to give them all the other things they need. Building strong systems is what will protect people, communities and the world.”

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Novel gene therapy treatment A novel gene therapy treatment for rare inherited eye disorder has been recommended by NICE for use on the NHS. The draft highly specialised technologies guidance recommends voretigene neparvovec (also called Luxturna and made by Novartis Pharmaceuticals UK) for people with vision loss caused by inherited retinal dystrophy from confirmed RPE65 gene mutations and who have enough viable retinal cells.

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Send them to our Editor, Ellen Rossiter, at ellen.rossiter@distinctivepublishing.co.uk

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Lucy O’Brien, Trainee Patent Attorney, AA Thornton Lucy works in the Chemistry, Life Sciences and Pharmaceuticals field and is involved in drafting and prosecuting patent applications before the UK and European Patent Offices, as well as working on opposition cases.

She also has experience in managing patent portfolios and has been involved in providing freedom-to-operate opinions to multinational corporations.

Jennifer Shelley PhD student at the University of Edinburgh in the Centre for Inflammation Research Having previously completely her BSc at University of Sheffield and MSc at Imperial College London, she now works on atopic dermatitis and hBD2.

Dr Gernot Walko Assistant Professor in Cell and Developmental Biology, University of Bath I am a skin biologist with expertise in epidermal stem cells, cell signalling and the cytoskeleton.

In my newly established research group, our research aims at understanding how the stem cell state in human epidermis is maintained throughout adult life, and what happens if we develop non-melanoma skin cancer.

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Professor Pietro Valdastri Professor of Robotics and Autonomous Systems at the University of Leeds.

He studied electronic engineering before specialising in biomedical engineering.

His extensive research has focused on the application of robotics to improve diagnosis and treatment. His more recent work involved the use of ‘capsule robots’: miniature devices for use in gastrointestinal endoscopy and surgery. He is pioneering the development of even smaller devices to give doctors access to areas deep in the lungs, heart and brain. He has won a number of prestigious academic research prizes.

Dr Jason Bellia Senior Patent Examiner at the UK Intellectual Property Office (IPO) He is responsible for search (for relevant prior art) and examination (leading to grant) of patent applications in the biotechnology and biopharma fields.

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Dr William Van’t Hoff Dr William van’t Hoff is an active paediatric researcher and has a long standing interest in involving young people in shaping clinical research. He is Consultant Paediatric Nephrologist at Great Ormond Street Hospital (GOSH) for Children NHS Foundation Trust London and Director of the NIHR GOSH Clinical Research Facility. In addition, he has also held local and national leadership roles in the National Institute for Health Research (NIHR) Clinical Research Network.

Professor Donald J. Davidson Chair of Host Defence & Inflammation Biology at the University of Edinburgh Centre for Inflammation Research and the Centre Academic Lead for Public Engagement He is a medically qualified researcher whose team focuses on understanding the function and therapeutic potential of Antimicrobial Host Defence Peptides in infectious diseases.

Professor James Wolffsohn Personal Chair in Optometry – Aston University

Fabio Kellet Director of Biosimilars at Napp Pharmaceuticals

Following a 1st class Optometry degree from Manchester, a professional year at Moorfields Eye Hospital, London, a PhD at Cardiff University and a clinical/research fellowship at the University of Melbourne, Australia, James was appointed by Aston University in 2000, where he was Head of Optometry 2004-9 and Deputy Executive Dean for Life and Health Sciences 2009-16, being awarded a personal Chair in 2007. He is now associate Pro-Vice Chancellor.

Fabio has a background in European Marketing and Sales, previously holding managerial positions in the areas of pain, primary care and addiction therapy. Fabio spent two years as Head of Sales – Biosimilars and held the position of Head of Biosimilars before moving into his current role.

Warwick Smith Director-General of the British Generic Manufacturers Association (BGMA) and the British Biosimilars Association (BBA) He is a member of the Board and Executive of Medicines for Europe – the European generic and biosimilar medicines association.

The BGMA launched the BBA four years ago to give a dedicated voice to the manufacturers of biosimilars medicines and to promote the creation of a balanced information resource.

Sarah Montague Originally trained as a Specialist Biomedical Scientist, Sarah worked at University College Hospital London and Great Ormond Street Hospital prior to working at King’s from August 2016. Her role is divided between research and service delivery. Sarah has recently completed an MSc at King’s College London in Implementation and Improvement Science and evaluated the acceptability of the Hepatitis C mobile outreach clinic amongst both patients and staff for her thesis.

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UEA scientists receive £7.4 million boost to combat ‘worst superbugs’ University of East Anglia scientists are developing a new wave of drugs to combat antibiotic resistance – thanks to a £7.4 million boost.

The overuse of antibiotics has made infections harder to treat, leading to thousands of deaths a year through drugresistant superbugs.

“This is a paradigm shift in research, and we have made a significant breakthrough in the race to solve antibiotic resistance.

Now, a spin-out company based at UEA’s Norwich Medical School is ‘shutting down’ the genes that cause antibiotic resistance.

“It is important because the problem of antibiotic resistance could take medicine back to the dark ages. Infections caused by multi-drug resistant bacteria lead to prolonged hospital stays, an increase in deaths and pose a major threat to global public health.

Researchers at Procarta Biosystems have discovered a new type of antimicrobial that kills bacteria, including multidrug-resistant Gram-negative strains, by blocking their gene expression.

Antibiotic resistance happens when bacteria acquire genes that protect them from the drug’s attack. They survive treatment and reproduce, spreading the key genes more widely so that drugs become increasingly less effective.

The UEA team hope that new drugs, which combat resistance by blocking gene expression in bacteria, will one-day help save lives by combating the world’s worst superbugs.

The funding comes from CARB-X (Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) - a global partnership dedicated to accelerating early research and development, to address the rising global threat of drugresistant bacteria.

The new funding complements a recent £1.3 million investment from Novo Holding’s Repair Impact Fund.

Procarta Biosystems founder Prof Michael McArthur, from UEA’s Norwich Medical School, said: “Antibiotics are important medicines needed to treat and prevent bacterial infections. They are very effective, but they also have a major weakness – bacteria acquire genes that protect them from the drug’s attack.

“Until now, part of the solution has been to develop new antibiotics, however there has not been a new class of antibiotic since the 1980s.

“We want to revolutionise the treatment of serious and lifethreatening infections in order to radically improve patient well-being and aid in the global fight against antibiotic resistance.

“If new drugs are not available soon, some infections could become completely untreatable and surgery and cancer therapy could become much more risky.”

Procarta Biosystems was founded in 2008 by Prof McArthur and Prof Mervyn Bib from the John Innes Centre, with seed funding from the UEA-based Iceni Seedcorn Fund and the UK Innovation & Science Seed Fund (ukinnovationscienceseedfund.co.uk).

The new funding will be used to progress the company’s pipeline of pre-clinical precision drugs to treat some of the world’s worst superbugs. These include potentially lifethreatening complicated urinary tract and intra-abdominal infections caused by a particular group of Gram-negative pathogens.

This group of pathogens – known collectively as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) are responsible for a significant proportion of infections throughout the world.

And they represent the greatest risk of antibiotic resistance of all clinical infections.

Prof McArthur added: “We are particularly concerned about a sub-group of Gram-negative bacteria called Carbapenemresistant Enterobacteriaceae (CRE), which are considered to be the worst new superbugs. These bacteria can kill up to half of the patients who develop bloodstream infections and worryingly, resistance in this group is growing exponentially.”

“Our aim is to create new drugs that shut down bacteria’s protective genes in order to stop antibiotic resistance.

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Turkish Cargo maintains its steady growth According to the data obtained by WACD, the international air cargo information provider, in May; Turkish Cargo, the global air cargo brand providing service to 124 countries around the world, increased its tonnage rate by 7.1 percent, and grew substantially across the industry which shrank by 5.1 percent in the global air cargo market.

Maintaining its steady growth as proven by the data disclosed right after its relocation to the Mega Hub Istanbul Airport, the accomplished air cargo brand increased its market share to 4.0 percent from 3.9 percent across the industry which shrank by 4.0 percent in the global air cargo market, and maintained its position at the 7th rank in the air cargo market.

RECORD-BREAKING GROWTH ACROSS THE ASIAN AND AMERICAN MARKET Based on the regional data obtained by WACD in May, Turkish Cargo achieved the most remarkable growth across the Asian and American market. The flag-carrier cargo brand attained a growth rate of 34.4 percent across

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the American Continent, 19.3 percent across the Far East Region, and 12.2 percent across the Middle East/South Asia Region as based on the sold tonnage. The accomplished air cargo brand achieved good results at all regions it provides air cargo service.

Operating direct cargo flights to 88 destinations by means of its fleet of freighters in addition to the cargo carrying capacity of the flag-carrier Turkish Airlines, the accomplished brand operates its dual-terminal operations from Ataturk and Istanbul Airports in 2019. Achieving a sustainable growth with its newly-launched destinations, current infrastructure and investments, Turkish Cargo keeps enhancing its capacity in more than 300 destinations included in its current flight network.

The outstanding air cargo brand, providing service to 124 countries, combines its wide range of services and operational capabilities with the unique geographical advantages of Turkey, and keeps setting the bar higher.

To view the flight schedules and details please visit www.turkishcargo.com.tr, or contact with the call center at +90 850 333 0 777.

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World’s largest genetics project launched A new ground-breaking project in the fight against life-threatening illnesses has just been launched.

The £200 million whole genome sequencing project is being created, forming a partnership of pharmaceutical firms and health experts which will examine and sequence the genetic code of 500,000 volunteers at the UK Biobank, based in Stockport.

Prime Minister Boris Johnson said: “Britain has a proud history of putting itself at the heart of international collaboration and discovery. Over 60 years ago, we saw the discovery of DNA in Cambridge by a team of international researchers and today we are going even further. Now we are bringing together experts from around the globe to work in the UK on the world’s largest genetics research project, set to help us better treat life-threatening illnesses and ultimately save lives.

“Its results could transform the field of genetic repeated research - unlocking the causes of some of the most terrible diseases and how we can best tackle them. It will be a major step forward for individually tailored treatment plans, and will help us better understand why some people get certain diseases while others don’t.”he UK Biobank recruited 500,000 people aged between 40 and 69 years between 2006 and 2010 from across the country. They have provided blood, urine and saliva samples for future analysis, detailed information about themselves and agreed to have their health followed on an anonymous basis.

Much of the sequencing will be by experts at the Wellcome Sanger Institute, based in Cambridge, and the results will help the NHS treat patients better.

“Breakthroughs of this kind wouldn’t be possible without being open to the brightest and the best from across the globe to study and work in the UK. That’s why we’re unveiling a new route for international students to unlock their potential and start their careers in the UK.”

Through the Biobank research, industry can work with experts to create new treatments and preventative measures which will help those suffering from illnesses and may eventually reveal why some people develop diseases and others do not.

Genomics research has the potential to create a genuinely predictive, more personalised healthcare system and the UK has a clear desire to seize the opportunities that research in this area offers, which is why the government has committed to carrying out five million analyses of DNA by 2024.

Funding for the genome project comes from a consortium formed by the government’s research and innovation agency, UK Research and Innovation (UKRI) with £50 million through the Industrial Strategy Challenge Fund, £50 million from the research organisation, Wellcome.

The new project aims to improve health through genetic research, improve the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses including cancer, heart diseases, diabetes, arthritis and dementia.

Business Secretary Andrea Leadsom said: “Today’s funding will support one of the world’s most ambitious gene sequencing programmes ever undertaken, reflecting the UK’s determination to remain at the forefront of scientific endeavour and progress.

A further £100 million has come from four of the world’s leading biopharmaceutical and healthcare companies Amgen, AstraZeneca, GlaxoSmithKline (GSK) and Johnson & Johnson.

The samples will be sequenced in equal numbers at the Wellcome Sanger Institute in Cambridge and the deCOde site in Iceland, from the genome sequencing company, Illumina.

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Repairing damaged hearts British Heart Foundation-funded research takes major step towards heart failure treatment.

A combination of heart cells derived from human stem cells could be the answer to developing a desperately-needed treatment for heart failure, according to new research partfunded by the British Heart Foundation (BHF) and recently published in Nature Biotechnology.

Researchers have found that, by transplanting an area of damaged tissue with a combination of both heart muscle cells and supportive cells taken from the outer layer of the heart wall, they may be able to help the organs recover from the damage caused by a heart attack.

Scientists have been trying to use stem cells to repair damaged hearts for a number of years. Efforts have been unsuccessful so far, mainly because the vast majority of transplanted cells die within a few days.

Now, Dr Sanjay Sinha and his team at the University of Cambridge, in collaboration with researchers at the University of Washington, have used supportive epicardial cells developed from human stem cells to help transplanted heart cells live longer.

regenerative power of stem cells, they will one day be able to heal human hearts using a patient’s own cells.

In addition to the BHF, this research was funded by the UK Medical Research Council (MRC) and the National Institute for Health Research (NIHR).

Dr Sanjay Sinha, BHF-funded researcher and leader of the study at the University of Cambridge, said: “There are hundreds of thousands of people in the UK living with heart failure – many are in a race against time for a life-saving heart transplant.

But with only around 200 heart transplants performed each year in the UK, it’s absolutely essential that we start finding alternative treatments.”

Dr Johannes Bargehr, first author of the study at the University of Cambridge said: “Our research shows the huge potential of stem cells for one day becoming the first therapy for heart failure.

Although we still have some way to go, we believe we’re one giant step closer, and that’s incredibly exciting.”

The researchers used 3D human heart tissue grown in the lab from human stem cells to test the cell combination, finding that the supportive epicardial cells helped heart muscle cells to grow and mature. They also improved the heart muscle cell’s ability to contract and relax (1).

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation which partfunded the research said: “Despite advances in medical treatments, survival rates for heart failure remain poor and life expectancy is worse than for many cancers.

Breakthroughs are desperately needed to ease the devastation caused by this dreadful condition.

In rats with damaged hearts, the combination also allowed the transplanted cells to survive and restore lost heart muscle and blood vessel cells.

Researchers now hope to understand how the supportive epicardial cells help to drive heart regeneration.

Understanding these key details will bring them one step closer to testing heart regenerative therapies in clinical trials.

Hundreds of thousands of people in the UK are living with debilitating heart failure, often as a result of a heart attack. During a heart attack, part of the heart is deprived of oxygen leading to death of heart muscle.

This permanent loss of heart muscle as well as subsequent scarring combines to reduce the heart’s ability to pump blood around the body.

People suffering from heart failure can’t regenerate their damaged hearts and the only cure is a heart transplant.

Ultimately, these researchers hope that, by harnessing the

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“When it comes to mending broken hearts, stem cells haven’t yet really lived up to their early promise. We hope that this latest research represents the turning of the tide in the use of these remarkable cells.”

The BHF has invested millions of pounds in research to harness the power of stem cells in treating heart and circulatory diseases. The charity has funded three Centres of Regenerative Medicine across the UK, housing some of the world’s leading experts.

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Genetic regions associated with left-handedness identified A new study has for the first time identified regions of the genome associated with left-handedness in the general population and linked their effects with brain architecture. The study, led by researchers at the University of Oxford who were funded by the Medical Research Council – part of UK Research and Innovation – and Wellcome, linked these genetic differences with the connections between areas of the brain related to language.

It was already known that genes have a partial role in determining handedness - studies of twins have estimated that 25% of the variation in handedness can be attributed to genes - but which genes these are had not been established in the general population.

Neuroimaging at the University of Oxford, said: “Many animals show left-right asymmetry in their development, such as snail shells coiling to the left or right, and this is driven by genes for cell scaffolding, what we call the “cytoskeleton”.

The new study, published in the journal Brain, identified some of the genetic variants associated with lefthandedness by analysing the genomes of about 400,000 people from UK Biobank, which included 38,332 lefthanders.

“For the first time in humans, we have been able to establish that these handedness-associated cytoskeletal differences are actually visible in the brain. We know from other animals, such as snails and frogs, that these effects are caused by very early genetically-guided events, so this raises the tantalising possibility that the hallmarks of the future development of handedness start appearing in the brain in the womb.”

Of the four genetic regions they identified, three of these were associated with proteins involved in brain development and structure. In particular, these proteins were related to microtubules, which are part of the scaffolding inside cells, called the cytoskeleton, which guides the construction and functioning of the cells in the body.

Using detailed brain imaging from approximately 10,000 of these participants, the researchers found that these genetic effects were associated with differences in brain structure in white matter tracts, which contain the cytoskeleton of the brain that joins language-related regions.

Dr Akira Wiberg, a Medical Research Council fellow at the University of Oxford, who carried out the analyses, said: “Around 90% of people are right-handed, and this has been the case for at least 10,000 years. Many researchers have studied the biological basis of handedness, but using large datasets from UK Biobank has allowed us to shed considerably more light on the processes leading to lefthandedness.”

“We discovered that, in left-handed participants, the language areas of the left and right sides of the brain communicate with each other in a more coordinated way.

This raises the intriguing possibility for future research that left-handers might have an advantage when it comes to performing verbal tasks, but it must be remembered that these differences were only seen as averages over very large numbers of people and not all left-handers will be similar.”

Professor Gwenaëlle Douaud, joint senior author on the study, from the Wellcome Centre for Integrative

The researchers also found correlations between the genetic regions involved in left-handedness and a very slightly lower chance of having Parkinson’s disease, but a very slightly higher chance of having schizophrenia.

However, the researchers stressed that these links only correspond to a very small difference in the actual number of people with these diseases, and are correlational so they do not show cause-and-effect. Studying the genetic links could help to improve understanding of how these serious medical conditions develop.

Professor Dominic Furniss, joint senior author on the study, from the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science at the University of Oxford, said: “Throughout history, lefthandedness has been considered unlucky, or even malicious. Indeed, this is reflected in the words for left and right in many languages. For example, in English “right” also means correct or proper; in French “gauche” means both left and clumsy.

“Here we have demonstrated that left-handedness is a consequence of the developmental biology of the brain, in part driven by the complex interplay of many genes. It is part of the rich tapestry of what makes us human”.

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UK lags behind Cancer survival in the UK has improved since 1995, although it still lags behind other highincome countries, according to new analysis by the International Cancer Benchmarking Partnership (ICBP), which is managed by Cancer Research UK. “More people than ever before are surviving cancer thanks to research and targeted improvements in care. But, while we’re on the right track, the numbers show we can certainly do better.” - Sara Hiom, Cancer Research UK’s director of early diagnosis The study, published in Lancet Oncology, looked at 3.9 million cancer cases between 1995 and 2014, in seven comparable countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK).

This is the first international study to look at changes in cancer survival alongside incidence and mortality for cancers of the oesophagus, stomach, colon, rectum, pancreas, lung and ovary. Exploring these three key measures allows us to better understand how countries like the UK compare in the prevention, diagnosis and treatment of different cancers.

Encouragingly, one-year and five-year survival has improved across all seven cancer sites in the UK across the 20-year period. Five-year survival for rectal cancer in the UK rose by 14 percentage points since 1995, from 48% to 62%.

The UK also has one of the highest increases in five-year survival - almost 12 percentage points - across all countries for colon cancer. This can potentially be attributed to advances in treatment such as better surgery, among other factors.

Additionally, one-year survival for lung, ovarian and oesophageal cancer all increased by around 15 percentage

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points in the last 20 years. Though great progress has been made, the UK remains near the bottom of the rankings, and has not yet caught up with the other countries.

Cancer Research UK’s clinical adviser, John Butler, who co-authored the study and is a consultant surgeon at the Royal Marsden, said: “There isn’t one specific reason why survival in the UK has improved - it’s a combination of many different factors. Over the last twenty years we’ve seen improvements in cancer planning, development of national cancer strategies and the rollout of new diagnostic and treatment services.

“For lung, ovarian, and oesophageal cancer in particular, survival has increased largely because the quality of surgery has radically improved, and more surgery is taking place than before. More people are being looked after by specialist teams, rather than surgeons who aren’t experts in that area.

But while we’re still researching what can be done to close the survival gap between countries, we know continued investment in early diagnosis and cancer care plays a big part. Despite our changes we’ve made slower progress than others.”

Sara Hiom, Cancer Research UK’s director of early diagnosis, said: “More people than ever before are surviving cancer thanks to research and targeted improvements in care. But, while we’re on the right track, the numbers show we can certainly do better.

“We will not see the necessary improvements in diagnosis and access to treatment unless we have enough of the right staff across our NHS. Cancer Research UK has been calling for staff shortages to be addressed because, quite simply, it will give people a better chance of surviving their cancer. If we are to achieve world class cancer outcomes in the UK, then we need to see comparable investment in the NHS and the systems and innovations that support it. It’s never been a more crucial time for the Government to put new money where it matters.”

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Treading the path less travelled – A different approach to patient recruitment In a previous issue, we spoke to Professor Miles Witham about his work to facilitate the participation of older people in clinical trials. Now we hear from Sarah Montague about a trial engaging homeless people in research.

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| patient recruitment |

Researchers face a challenge striking the balance between getting people to participate and getting the appropriate people to participate. If they set the criteria for participation too broad, their data may not be reliable enough to answer their question. Too stringent, and they may not be able to recruit enough patients.

The National Institute for Health Research (NIHR) Clinical Research Network (CRN) South London helps to increase the opportunities for people to take part in clinical research.

The NIHR CRN South London is supporting a project taking a different path to recruitment; The Access To Treat in the Community (ATTIC) trial.

Sarah Montague, Research Associate and Clinical Trials Manager at King’s College Hospital NHS Foundation Trust explains more about their work.

“Typically, clinical trials have strict criteria for participation, with a lengthy document outlining what’s required of a candidate. These parameters tend to be specific and unbending in terms of who’ll they’ll accept, meaning few people meet the requirements.

“In addition to which, the practicalities of attending multiple appointments at hospital presents another set of challenges, with lifestyle, mobility, the cost and difficulty of accessing transport all preventing involvement.

“Our trial aims to remove these barriers by taking our trial to people, rather than expecting them to come to us. We also take a different approach to recruitment by recognising and accepting that many of our participants face multiple challenges from mental health issues to drug dependency.

By doing so, we are engaging with a much underrepresented group in clinical trials, the homeless.”

The ATTIC trial aims to test and treat homeless people with Hepatitis C in areas where infection rates are high. In doing so, the trial is supporting NHS England’s ambition to eliminate the virus as a public health threat in England by 2025, and the World Health Organisation’s global goal of 2030.

Crucially, the trial clinic is mobile, using a converted bus as its base, enabling the team to reach participants more easily.

Supported by CRN South London, the bus is run day-today by a joint team from the King’s College Hospital NHS Foundation Trust, supported by The Hepatitis C Trust.

When the trial began in late 2018, the bus initially visited homeless shelters and day centres and Sarah is quick to remark how helpful local homelessness organisations have been in helping them engage with the homeless community. As time progressed and the team knew the community better, they began taking the bus directly to the homeless, at local railway stations, for example.

Barriers to participation were also reduced by keeping the paperwork, tests and criteria to an absolute minimum. A

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simple finger prick test is used to test for the Hepatitis C antibody, giving a result that is ready in a mere 15 minutes.

If the test proves positive, then further blood tests are undertaken.

Not only does this trial represent a sea change in how a trial is carried out, but it also represents a change in attitude to treatment accessibility. “Previously, some patients with Hepatitis C were expected to live with the condition due to the poor treatment options,” explains Sarah. “In the last few years, however, treatment has progressed, Hepatitis C can be treated quickly and effectively and there are fewer unpleasant side effects than was once the case.”

For those who test positive, treatment is given by the healthcare team working from the bus, no hospital visits are required. The tablet antiviral drug Zepatier is used to treat people with the genotype 1a, 1b and 4 Hepatitis C infection, stopping the virus from multiplying. 12 weeks after the course of Zepatier is completed, patients have a blood test to determine whether they have been cured. Whilst those with a different genotype access standard NHS treatment.

“The aim of this trial is not only to increase testing, so we can discover new cases, but also to demonstrate we can deliver Hepatitis C treatment to the homeless community away from the hospital in the community,” observes Sarah.

Improved detection and inclusivity are crucial as an estimated 113,000 people are living with the virus in England, around half of whom are undiagnosed. Left undiagnosed and untreated, HCV can be extremely damaging, potentially causing fatal cirrhosis and liver cancer. Reaching more people, earlier in the disease progression and being inclusive in the delivery of treatment is vital.

The ATTIC trial also focuses on enabling participants to complete their treatment, with the on-board healthcare team providing extensive follow-up and support. Working flexibly is also required to meet the needs of the community, dispensing a month’s worth of treatment, for example, proving impractical when the recipient has nowhere to store it, so some standard procedures are being rethought.

Peer support plays a particularly significant role, with a key member of the on-board team having experienced both homelessness and hepatitis. Whilst the project also demonstrates the value of nurses working in the community.

The success of the project indicates that in this area at least, the typical model of outpatient care needs changing. Whilst the multi-agency approach, with the NHS, charities and other local organisations working together, speaks volumes about how best to deliver both a trial and treatment. As for the ATTIC bus, the wheels will keep turning for the rest of the year and potentially beyond.

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Patient recruitment: The balancing act

Well conducted patient and public engagement can have a positive impact on recruitment and retention. To really increase your chances of success you need to be engaging patients as early as possible in the clinical development process, says Dr William Van’t Hoff, a Clinical Director in the National Institute for Health Research (NIHR) Clinical Research Network.

In the UK, the NIHR has made huge efforts to improve recruitment into clinical trials over the last decade, with justifiable success. Last year the National Institute for Health Research (NIHR) Clinical Research Network (CRN), published record levels of research participation. Over 870,000 people took part in clinical research (including both commercial and non-commercial) during 2018/19, a 54 per cent increase from 2010/11. Drilling down to commercial contract research alone reveals an impressive 229 per cent increase in recruitment to 46,064 participants in 2018/19 from 13,987 over the same period.

Whist we celebrate these results, it is also important to focus on the need to further improve our performance in the set-up and delivery of research – offering research to participants quicker and completing studies to time and target is important to patients and industry alike. Working with patients can help enhance our performance. We use the term ‘patient engagement’ to talk about this important relationship between patients and the life sciences industry. Other terms may be used in other contexts but the key thing is the principle underpinning the approach, which is about collaborating with patients and the public throughout research design and delivery, rather than doing research ‘to them’ or ‘for them.’

In the UK meaningful patient engagement has been taking place across the NIHR for over twenty years; NIHR Involve1 was created in 1996. Activities such as research priority setting, advising on recruitment strategies and reviewing the wording of patient information leaflets have become commonplace. Yet it’s fair to say that patient engagement has, to date, been more visible in non-commercial research (funded by government, universities, research charities) than in commercial research (funded by the life sciences industry). This needs to change if the UK is to maintain its position as a global leader in clinical research delivery.

As a paediatrician and a researcher, I really see, and experience, the challenge of conducting clinical trials with children. There are many factors which influence the family’s decision whether or not to take part, but I would say that first and foremost we need to ensure that the ‘ask’ of the research is balanced with the burden of the disease.

For example, for a life-limiting disease like cancer you might expect a trial to be quite intensive in terms of treatment sessions, hospital visits and tests. But that same regime would be less acceptable for a long term condition like asthma, which many people manage with medicine, at home, on a daily basis. If we have a mismatch, in other words if the ask of the research is heavy where the burden of

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Throughout 2018 we collaborated with patients and a global pharmaceutical company, Pfizer Ltd, to design and pilot this new service. The pilot involved two Pfizer studies looking at a new treatment for eczema which were both paediatric and adult studies. The NIHR Clinical Research Network team facilitated two meetings at Alder Hey Children’s Hospital NHS Foundation Trust, Liverpool, firstly with a group of young people2 and then with a group of parents/carers.

Dr William Van’t Hoff

Sophie Evett

the disease is light, patients are less likely to participate and it will have a significant impact on a study, from approvals right through set-up and recruitment.

It’s really important to prevent a mismatch from happening and I believe the key is to ensure that there is an opportunity for patient engagement and input to protocol review.

Spending time consulting with patients, representative of potential participants, should reap dividends in a study set-up and delivery. Patient’s experience of their disease and its impact on their daily lives can really help us achieve the right balance between the ‘ask’ of the research and the burden of the disease.

However, bringing patients and life-sciences’ researchers together is not easy and needs to be done appropriately.

Some members of the public are unclear or suspicious about what motivates and drives the life science industry and how they operate. Codes of practice and regulations governing the life science industry, which are entirely appropriate, may seem like an impediment to this form of engagement at times. When the NIHR Clinical Research Network team held discussions with industry representatives about patient engagement, a number of practical issues were raised. These included: Identification of patients/public who are willing and able to work with industry Managing the legal requirements, professional standards and commercial sensitivities, often across different nations Appropriate formats companies should use to communicate and work with patients/public Recompense and thanks for patients/public for their time, commitment and expertise Public perception of patient engagement with the pharmaceutical industry Cost-effectiveness in the absence of clear evidence of positive impact Last October the NIHR Clinical Research Network announced a pilot project which aimed to address some of these challenges while focusing on facilitating patient and public engagement activities earlier in the clinical development process – specifically at the protocol review stage. The initiative’s long term aim is to create a level playing field, on a national scale, in which patient engagement activities can take place unhindered.

“...first and foremost we need to ensure that the ‘ask’ of the research is balanced with the burden of the disease.”

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Sophie Evett, Feasibility Lead for Pfizer UK, who led Pfizer’s participation in the pilot, said: “At the study level, the clinician who wrote the protocol met with both patient groups in person, as did my colleague who supports recruitment for Pfizer globally. They were surprised at some of the questions they were asked by the young people in particular. Some of the questions were very scientifically technical, for example around how the drug might alter your immune system and what effects that might have on the body. The young people were not afraid to say what they felt and were very clear about what they wanted to see included in the informed consent and assent document. For the adult study, one element of the draft protocol relating to prohibiting other medications was amended as a direct result of engagement with the parents/carers, and the study has since been approved to move to site selection stage.

“Looking at the pilot more broadly, it took a little longer than expected to satisfy our legal and compliance teams initially, mainly because it was a completely new way of working. However, it was a worthwhile exercise because it has enabled us to work through the many legal and compliance challenges and develop documentation that we can use time and time again for patient engagement activities, regardless of the study, patient group or therapeutic area.”

A review of the pilot suggests that one of the factors contributing to successful engagement between early-adopter companies and patients is the role of an independent ‘go-between’ or facilitator – a role which the NIHR Clinical Research Network is undertaking. Keith Wilson, Patient Research Ambassador for Liverpool Heart and Chest Hospital NHS Foundation Trust, worked with NIHR Clinical Research Network on developing the pilot.

Keith explains: “The main challenge in the past has been around trust.

Patients and the public have historically been wary of the life sciences industry, and some may still harbour some misconceptions.

“I thought the pilot was a great idea and long overdue but, at the same time, I was initially sceptical that the project would achieve the desired outcomes. However, having the NIHR Clinical Research Network – which has worked in partnership with our NHS for over a decade – facilitate the service has made an enormous difference. Patients love their NHS, and if the approach comes from the NIHR Clinical Research Network, patients and members of the public are more open to having those direct discussions with life sciences companies. The NIHR Clinical Research Network is absolutely instrumental and fundamental to brokering that deal.”

The pilot continues and is expected to publish case study material by the end of the year describing how this patient engagement process has an impact on clinical trial design.

The ambition is then to establish a national framework for earlier patient engagement by 2020, with the CRN providing a clear route for life sciences companies to connect with relevant patients to help ensure patient-friendly clinical trial designs. www.nihr.ac.uk 1. https://www.invo.org.uk 2. YPAG - Young Person’s Advisory Group https://www.invo.org.uk/ypag-the-young-persons-advisory-group

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A British Skin Foundation funded project into atopic eczema Human beta-defensin in Atopic Dermatitis: dissecting the mechanism of a novel, targetable, protection against skin barrier damage. need to be used long-term from an early age. Therefore, it is really important that these treatments are safe and well tolerated.

AD costs the NHS over £47 million/year, with use of corticosteroids on the skin being the current main form of treatment. These can work well for a lot of people, but they can have damaging side effects over long term use, including interfering with the body’s natural responses to skin infection. In addition, in some people, these corticosteroids do not work well or they stop being effective.

There are not many other good treatment options for these people and those that are available can have more harmful side effects. For most of the people you know that have eczema, the condition may seem like a relatively minor problem. But, for a significant proportion, the disease can be very extensive, painful, hard to treat and have a genuinely disabling impact on their lives.

Dr Donald J. Davidson is an Inflammation Biologist and Senior Researcher at the University of Edinburgh Centre for Inflammation Research. Dr Davidson was awarded a British Skin Foundation Large Grant, entitled ‘Human betadefensin in Atopic Dermatitis: dissecting the mechanism of a novel, targetable, protection against skin barrier damage’, supporting a PhD student, Jennifer Shelley, to conduct research into this topic, starting in the autumn of 2018.

Here Donald and Jennifer explain the research in more detail and what they hope they can achieve.

WHAT IS THE PROBLEM? Atopic Dermatitis (AD), commonly known as atopic eczema, is a common, distressing skin disease. We all know somebody affected by it or have experienced it ourselves. It results in areas of itchy, red, broken skin, typically on the face, scalp and limbs, where the skin is inflamed. In the UK, as many as 20% of children, and up to 10% of adults, have AD. AD is a chronic condition, so it flares up repeatedly and can affect people for their whole lives. As a result, treatments

It is therefore clear that medical researchers and clinicians need to development new therapies for AD. This will be done most effectively if we have a stronger understanding of how the disease develops and progresses, and what prevents it from occurring in people who are not affected. We can then target new treatments based on that knowledge.

Funding for research in this area, such as grants from the British Skin Foundation (BSF), enables laboratories like ours to try to start to tackle this problem. In this manner, the BSF can translate donations and the fund-raising work of their supporters into efforts to improve the lives of individuals with AD in the future. Research can be a long hard process, but it offers a light at the end of the tunnel.

HOW CAN WE TRY TO TACKLE THE PROBLEM? One important feature of AD is disruption to the barrier function of the skin. Recent clinical studies suggest that restoring and/or maintaining effective skin barrier function is a promising strategy to explore. Skin barrier disruption in AD has been linked to a wide range of factors, including environmental irritants, and an individual’s genetics. It

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AD COSTS THE NHS OVER £47 MILLION/YEAR

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can also be affected by skin infections and by the types of bacteria an individual has living on their skin; some of which seem to be more protective, while others may be more harmful. For example, the bacteria Staphylococcus aureus, more commonly found on the skin of people with AD than those without AD, can produce barrier-damaging substances called proteases that may contribute to the disease process. If we can find ways to block the barrier damage caused by these proteases, and to tip the balance towards more protective bacteria on the skin, perhaps we can move towards new treatments for AD. But what kind of substances could have those properties?

Donald, and the researchers he works with, study substances called Antimicrobial Host Defence Peptides (HDP). These are naturally produced by all animals, and even by plants. HDP can kill harmful bacteria, viruses and fungi, can alter the balance of the types of bacteria living on our bodies, and can direct and adapt the approaches our bodies choose to use to fight infections. The team discovered that one HDP, called human beta-defensin (hBD)2, can also protect the skin barrier from damage caused by proteases in a laboratory setting. Intriguingly, this hBD2 is produced naturally by the skin, and, whereas healthy skin makes more of it when faced with

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inflammation, damage or infection, AD skin is less effective at responding in this way and launching a protective hBD2 response. So, can studying hBD2 help us develop a new treatment for AD, based on a naturally occurring skin HDP? Might it help kill harmful bacteria, select for more protective bacteria, and block the damaging effects of bacterial proteases to protect the skin’s barrier function? That’s what our team are hoping!

Jennifer started her PhD in the autumn of 2018. With supervision from Donald and other members of the group, she is now getting to grips with the varied laboratory techniques required to start to develop this research proposal. It is early days. But, as she learns these skills and a working knowledge of the research topic, she has the type of exciting future prospects that sustains a medical researcher through the days when experiments are not working; namely that, thanks to BSF funding, she just might make the kind of breakthrough that ultimately leads to the development of a new, safe, long-term treatment approach for AD. For more information see Donald’s websites at: www.djdavidsonlab.net www.ed.ac.uk/inflammation-research/people/principalinvestigators/dr-donald-j-davidson

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many layers to cancer research Dr Gernot Walko, is a skin biologist and Lecturer in Stem Cell Biology at the University of Bath. In 2017, Dr Walko was awarded a British Skin Foundation small grant for his research, ‘Targeting YAP/TAZ as a novel therapeutic strategy in cutaneous squamous cell carcinoma.’ Here he explains in more detail about the research and what he hopes it can achieve. to grow out of control, invade surrounding tissues and spread through the body.

Skin cancer is the most common cancer world-wide, and rates continue to rise by 2-4% each year. There are two main categories of skin cancer: melanomas and non-melanoma skin cancers (NMSCs) often now also termed keratinocyte cancers. Cutaneous squamous cell carcinoma (cSCC) is a NMSC and originates from the epidermal keratinocyte. cSCC is the second most common skin cancer in the UK and world-wide. cSCC can be cured by surgical removal if detected early. But if left untreated and the cancer cells spread to other parts of the body, no effective treatment is available. This is serious, resulting in death in 70-89% of patients.

Dr Gernot Walko Skin is a very important organ in our bodies. It protects us from infection and dehydration, and allows us to feel many different things, such as pressure or heat. In humans and other mammals, the skin has three tissue layers - the epidermis, the dermis and the subcutis (or hypodermis). The epidermis forms the surface of the skin.

It is made up of several layers of specialised cells called keratinocytes.

Most of the work in the cells of our body – including keratinocytes – is done by proteins, which are a huge, varied group of molecules. Therefore, the thousands of genes expressed in a particular cell determine what that cell can do. The instructions for how to make proteins comes from genes. The process by which the information in a gene is turned into a functional protein is called gene expression. Gene expression is a tightly regulated process that allows a cell to respond to its changing environment.

Only a fraction of the genes in a cell are expressed at any one time, and differences in gene expression programmes determine the distinct functions of different cell types.

In all types of cancer, some of the body’s cells begin to divide without stopping and spread into surrounding tissues. As a result of altered gene expression, cancer cells differ from normal cells in many ways that allow them

Two proteins called YAP and TAZ contribute to initiation, progression and body-wide spread of cSCC as well as many other cancer types. YAP/TAZ work in the cell’s nucleus where they interact with many other proteins to promote the expression of genes that allow cancer cells to grow, divide, migrate and spread to other body parts. YAP/TAZ appear not to be involved in the maintenance of normal healthy epidermal tissue, but they are essential for cSCC development and progression. This makes them ideal targets to develop treatments for cSCC and other cancers.

RESEARCH INTERESTS OF MY LAB How YAP/TAZ control gene expression in the nucleus represents a largely unexplored but promising area to design new modalities of therapeutic anti-cancer interventions. In our current British Skin Foundationfunded project my lab first aims to identify all the different proteins that YAP/TAZ interact with in the nucleus of normal healthy keratinocytes to control gene expression in these cells. We will then monitor how the interaction partners of YAP/TAZ change as keratinocytes become more and more abnormal during development of cSCC and eventually turn into aggressive cells that can invade neighbouring tissues. This strategy should enable us to identify and characterise cSCC-specific nuclear YAP/TAZ binding partners as novel candidate targets for the design of therapeutics to treat cSCC and other cancers.

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In the blink of an eye Blinking an eye may seem a simple action, but in this issue, we learn how imperative it is for eye health. Professor James Wolffsohn, Chair of Optometry and associate provice-chancellor of Aston University, casts a fresh pair of eyes on Dry Eye Disease and explains the role of blinking in relieving symptoms. Here, he speaks to Ellen Rossiter, about the research work ongoing to define and treat the condition.

DRY EYE DILEMMA “Affecting hundreds of millions of people around the world, Dry Eye is one of the most common reasons for a visit to an eye care practitioner,” explains James, “and given the volume of people affected, finding effective preventative measures and treatments is vital.

“Resulting in dryness and inflammation of the cornea; Dry Eye Disease is caused by a chronic lack of lubrication and moisture on the eye’s surface. Typically, the disease causes irritation, soreness and sometimes even watery eyes.

“Left untreated, the disease can cause damage to the eye’s surface, and in some instances, vision problems. However, when you look at the ocular surface, some patients with severe damage have relatively few symptoms, meaning cases are often not picked up until later in the disease’s progression.

“Estimates for the numbers of people affected range from 5% to 50% of a population in different parts of the world, with most studies estimating around 15% of Caucasians and 30% of Asians have the disease. A lot of clinical trials, however, have previously failed to standardise what they are looking for, so the prevalence and severity of the disease remains a topic for debate.

“The variation in world-wide figures is thought to be down to several factors including a lack of uniformity in the diagnosis criteria and the impact of environmental factors such as humidity. So part of our work has focused on creating clear criteria for diagnosing Dry Eye.”

CONSENSUS WORLD-WIDE “Taking over two years and involving over 150 experts, the Dry Eye Workshop II of the Tear Film and Ocular Surface Society has worked to achieve a global consensus concerning the multiple aspects of the disease.

“As well as updating the definition and classification of Dry Eye Disease, those of us involved, evaluated the information available on the distribution, development, processes and impact of the disease.

“With the work that’s been done, we’ve now classified a spectrum between two types of the disease, one where the eye doesn’t produce enough tears and one where tears aren’t retained for long enough by the eye largely due to evaporation.

“The review of all the science on the disease to date identify around 50 possible treatments and a huge matrix of information about their effectiveness, but there is still a lack of clarity about which should be used for a particular patient. Much better guidance on treatments is required, so people have certainty about which to choose and for how long it should be used.

“When we look at artificial tears alone, there are hundreds of options available, so we’ve looked at which treatments work, for whom and what are the most effective components. As a result of this research, we’re developing new artificial tears to treat the condition.”

CHANGING DEMOGRAPHICS “Dry Eye Disease tends to be experienced by people working in air-conditioned environments, who wear contact lenses or who work at computer screens and it’s typically associated with those aged over 50.

“A worrying trend has recently emerged of young people suffering from the condition, presumed to be due to their prolonged screen time. Spending too much time at a computer, looking at a phone or tablet, is known to affect the frequency and completeness of our blink rate, which in turn affects the tear film.

“Blinking may seem a straight forward action we take for granted, but it’s one of the body’s great defence mechanisms and has many benefits for eye health.

Increasing moisture, fighting infection, flushing debris, clearing vision, maintaining comfort and restoring the transparency of the cornea are all brought about by blinking.”

“Blink exercises are thought to be effective in reducing the disease’s effects but there is no research to show this is the case, so in one study we are evaluating the optimum way to

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TAKING OVER TWO YEARS AND INVOLVING OVER 150 EXPERTS, THE DRY EYE WORKSHOP II OF THE TEAR FILM AND OCULAR SURFACE SOCIETY HAS WORKED TO ACHIEVE A GLOBAL CONSENSUS CONCERNING THE MULTIPLE ASPECTS OF THE DISEASE.

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carry out blink exercises and the frequency with which they should be carried out.

working on reducing the loss of contrast and optimising how these lenses work.

“We’ve also developed an app which patients can use to establish if they are likely to have Dry Eye Disease called the blink test, which has proven a quick and accurate way to identify the disease and particularly helpful where clinicians don’t have access to advanced instrumentation.”

“Another huge area of interest is myopia or shortsightedness, as an increasing number of people are affected; in some areas of Asia, for example, it’s estimated that 95% of children are short-sighted.

A BROADER VIEW “Investigating Dry Eye Disease is just one facet of our Ophthalmic research at Aston; we’re working to advance our understanding of many aspects of the development, use, preservation and restoration of ocular function.

“As well as the tear film, my research focuses on intraocular lenses (used in cataract operations), contact lenses, developing ophthalmic instrumentation and the impact of ageing on eyesight.

“We know people tend to experience a loss of eye focus around the age of 40 and glasses with varifocal lenses often assist with the challenges this brings. Given the popularity of contact lenses, developing varifocal options has been a priority.

“In some instances, the options available, are associated with blurred vision at some distances and scatter of light such as when night driving, so this is another of our research area. Light levels and distances can all prove problematic for varifocal contact lens wearers, so we’re

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“Over the last decade, there’s been a growing understanding of what causes short-sightedness, so there is much research underway about how best to prevent, slow or halt the progress of myopia and the eye damage it causes.”

LOOKING TO THE FUTURE “In terms of inspiring the next generation, I’d say the great thing about STEM subjects is the sheer variety of careers to which they open doors. Optometry itself offers great opportunities for those interested to go down that path and given our work often improves peoples’ quality of life, quickly, it is deeply rewarding.

“Clinicians are much like engineers, providing solutions for the challenges faced in healthcare. As well as understanding diseases better and translating research into new treatments, much research work is about making treatments accessible.

“Not all medical advances depend on cutting edge technology or are expensive. One of my most surprising findings was discovering how effective a heated bag of beads placed over the eyelids for 5 minutes in the morning and evening for 2 weeks was in restoring the tear film.

Sometimes it’s the simplest things that work best.”

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Biosimilars set to make significant UK impact Biosimilar medicines - equivalent biological products which have no meaningful differences from the original or reference product in terms of quality, safety or efficacy - are playing an important role in providing choice for clinicians and increasing access for patients by driving down cost to the NHS. Warwick Smith, director general of the British Biosimilars Association (BBA), outlines how the UK has grown into a market leader.

The patent expiry of Humira, one of the world’s bestselling medicines, at the end of last year was rightly anticipated as a milestone moment for the biosimilars sector. A biological blockbuster used the world over was now open to competition and the introduction and uptake of alternative biosimilars was also going to be viewed as a measure of progress in the development of these important follow-on medicines.

Nearly a year on, progress been good and Adalimumab the biosimilar name for Humira – is on course to make the single biggest contribution to the NHS objective of saving in the order of £200 million to £300 million per year by 2021. Biosimilars are here to stay and will make significant contributions to NHS sustainability moving forward.

Biological medicines are protein based and made or derived from living organisms. Unlike traditional chemical equivalents, they can be tailor-made so they bind to

specific targets in the body and treat serious or chronic diseases. A biosimilar medicine is manufactured to be highly similar to an existing licensed “reference” biological medicine after expiry of its patent, with no meaningful differences in terms of quality, safety or efficacy.

Biological medicines - like Humira - have dominated global lists of the best-selling, highest cost prescription drugs. Very successful treatments for rheumatoid arthritis and autoimmune diseases have led the way and as we move forward other disease areas, such as oncology, are increasingly coming to the fore in new biosimilar medicines.

With UK healthcare budgets stretched by ageing populations, technology investment and advances - which mean diseases can be detected earlier and treated later - affordability and value are key elements of widening patient access. So, as biological medicines  page 28

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“With UK healthcare budgets stretched by ageing populations, technology investment and advances - which mean diseases can be detected earlier and treated later - affordability and value are key elements of widening patient access.”

Warwick Smith

 from page 27 have played a more significant role in providing lifesaving and life-enhancing treatments, greater uptake of biosimilar medicines is critical and this is an area where the UK will see increasing benefits over the next few years.

important and we have seen the most effective uptake in the UK where commissioners and medical professionals work together to implement biosimilars and share the resulting savings across their respective institutions.

However, this kind of progress and cut-through has not always been the case for the UK market which just a few years ago was some way behind usage and uptake of biosimilars compared with other European countries.

Uptake is now in a healthy state and in a relatively short space of time the UK has gone from lagging to leading. That said complacency isn’t creeping in and there is still much to do to correct regional variations and ensure patient groups and clinicians are able to learn from the experience of those that have gone before as patents expire in new therapeutic areas.

Lack of comparable clinical experience and thus real word understanding had previously been among the limiting factors for biosimilar uptake. Some clinicians and patients had been more cautious to embrace them.

However, as experience has increased, so has understanding, particularly around topics such as switching patients from the originator to a biosimilar medicine, which is needed to drive the full benefit of biosimilars in enhancing patient access. NHS England has done a great job in bringing together the full range of stakeholders NICE, the MHRA, industry groups, patient groups, doctors and nurses - to understand why biosimilar medicines should be routinely adopted, and why switching from the originator is a perfectly natural thing to do, that is underpinned by the regulatory science and now increasing real world evidence.

NHS England has issued guidance for commissioners which suggests that it should be normal for new patients to be treated with biosimilars - if they are less costly than the originator, which they normally are – and that clinicians should consider switching existing patients from the originator to a biosimilar. This kind of guidance and sharing of best practice has been key to driving further uptake across the regions of the UK. The NHS has recently published the second iteration of its “What is a biosimilar” document aimed at increasing clinical and patient awareness.

From a procurement perspective, there is also innovation being rolled out. Due to the sheer scale and cost of Humira / Adalimumab, NHS England adopted a new approach to procurement: one which prioritised competition, and therefore savings to the NHS, but also crucially focused on ensuring that there were multiple suppliers, avoiding a “winner tales all” approach. This assisted sustainability for the industry and security of supply for patients.

Learnings from these products are being taken on-board and will be translated into future biosimilar launches. Fine tuning and re-shaping future processes is important in order to deliver the right level of incentives and benefits across the system which in turn will drive uptake and savings, benefitting NHS budgets and patient access.

The biosimilars market in the UK has seen rapid acceleration in recent years and is now in a position to deliver significant savings which will increase access and support sustainability of the wider NHS. www.britishbiosimilars.co.uk

This collaboration between stakeholders has been

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| biosimilars |

More than £700m saved The NHS has saved more than £700 million from the annual medicines bill to reinvest in new treatments as part of the Long Term Plan.

An NHS-wide campaign has supported patients and doctors to maximise the use of ‘generic’ and best value ‘biologic’ treatments to treat conditions including arthritis and cancer.

New figures show that the uptake of best value medicines lowered costs to taxpayers by £294 million last year alone, on track to meet its ambitious target of a further £400 million annual savings by 2021.

A single drug - adalimumab - treatment for arthritis and other diseases, saved £110 million alone thanks to a ‘smart procurement’, after the drug came off patent at the end of 2018.

Previously adalimumab was the individual medicine on which hospitals spend the most, at a cost of more than £400 million a year.

Simon Stevens, NHS chief executive, said: “The NHS is one of the most efficient health services in the world but as part of the Long Term Plan, we will continue to drive changes to ensure every NHS pound is spent wisely and patients have access to innovative life changing medicines.

“Use of the best value versions of expensive medicines is already delivering effective treatment for patients across the

NHS, including those with cancer, offering the right care for patients while saving the tax payer hundreds of millions of pounds.”

The savings for 2018-19 come on top of the £413 million saved from the annual medicines bill in the previous two years by maximising the use of best value generic and biologic treatments.

Taken together the savings mean the campaign to drive take-up has seen more than £700 million freed up to reinvest in other effective medicines.

NHS England has previously announced plans to accelerate and widen the uptake of best value biologic medicines in a bid to save £400m to £500m per year by 2020/21.

This money can be then be reinvested in other new, innovative and cost-effective treatments.

These benefits have only been possible by working closely with patients, clinical teams and NHS trusts.

The decision to switch to a best value medicine should always be done in consultation with the patient, through shared decision making.

Medicine

Treats

2018-2019 savings delivered

Adalimumab best value biologic uptake

Rheumatoid diseases, dermatological and inflammatory bowel diseases

£109,668,408

Infliximab best value biologic uptake

Rheumatoid diseases and inflammatory bowel diseases

£31,964,413

Etanercept best value biologic uptake

Rheumatoid diseases

£36,077,607

Rituximab best value biologic uptake

Certain cancers and rheumatoid conditions

£45,174,920

Imatinib generic uptake

Types of cancer

£18,848,913

Linezolid generic uptake

Types of bacterial infection

£2,037,999

Prednisolone Soluble

Asthma

£37,786

Valganciclovir generic uptake

Types of fungal infection

£3,833,955

Voriconazole generic uptake

Types of fungal infection

£6,983,219

Caspofungin generic uptake

Types of fungal infection

£8,485,062

Trastuzumab best value biologic uptake

Breast cancers

£24,254,902

Total

£293,785,789

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| biosimilars |

| BIOSCIENCE TODAY |

Moving healthcare forward

Making cutting edge treatments accessible to more patients, is one of the greatest challenges facing the healthcare system and biosimilars are playing a part in making this possible. In this issue, we speak to Fabio Kellett, Director of Biosimilars at Napp Pharmaceuticals Ltd about the development of biosimilars and how they are enabling more patients to be treated.

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| biosimilars |

“Our services go far beyond bringing a product to the market. We dedicate our time and resources to providing information, education and support, because we believe that adding value is about more than just price. By providing value through support programmes and educational activities, we can build confidence in biosimilars and the role they can play in improving patient outcomes. It is this wraparound service and our commitment to embedding biosimilars, that makes Napp stand out from our competitors and so often makes us the partner of choice.

Fabio Kellett

Director of Biosimilars at Napp Pharmaceuticals

“We foster a flexible culture at Napp where our people thrive on the ability to be agile and autonomous in response to the needs of our partners. What speaks volumes about the company is the low turnover of staff, as people stay with us for the long term. Few biosimilars teams in the industry have stayed as one unit for so long, providing stability for our customers and meaning our decades of experience informs every project.”

PIONEERING BIOSIMILARS BACKGROUND ON BIOSIMILARS “Biosimilars have been around for over a decade,” explains Fabio. “Whereas generic medicines contain active ingredients that are chemically identical to the originator medicine, biosimilars, as the name suggests, are similar, but not identical to the original biologic. Since biological products are a complex combination of materials which are active substances derived from living cells or organisms, they may show a certain degree of variation, even between batches of the same product.

“A biosimilar medicine is a biological medicine which has been shown not to have any clinically meaningful differences from the reference medicine in terms of quality, biological activity, safety, efficacy and immunogenicity.”

MAKING A POSITIVE DIFFERENCE “The NHS is one of the biggest health care economies in the world, and understandably empirical evidence is required to make new treatments available. The beauty of biosimilars is that they enable this to happen sooner, so biosimilars are making a positive difference to patients and the NHS, as more patients can access more advanced treatments.

“This is because, when compared to the high cost of developing and manufacturing medicines, biosimilars are cost-effective. The NHS has been able to make huge savings by using the best value treatments available, whether they are generics or biosimilars. Collectively the use of generics and biosimilars are estimated to have saved the NHS a staggering £700m since 2016.

“Our agility and autonomy were instrumental to us becoming one of the first pharmaceutical companies to launch a biosimilar monoclonal antibody (mAb). A more recent phenomenon within the family of biosimilars, the first of the mAbs became available in Europe as recently as 2015, when we brought the first large molecule biosimilar for rheumatoid arthritis to the UK market.

“Larger, more complex structures than other biosimilars, you might equate developing mAbs with working on a jumbo jet rather than a small car. Used by the immune system to fight diseases, mAbs have proven particularly effective in treating cancer and rheumatoid arthritis.

“Our biosimilars capability has remained a central part of our business and this year Napp became the third largest provider of mAbs in the UK.”

DELIVERING BETTER HEALTH OUTCOMES “Overall, given biosimilar mAbs provide equivalent treatment, but are more cost-effective than the originators, they provide benefits for both patients and the NHS. More people can benefit from treatment, potentially sooner, thereby delivering better health outcomes, as well as freeing up precious resources for additional research work.

“In short, biosimilars help to move medicine forward, which is our purpose as an organisation and they have a significant role to play in making the NHS sustainable.

That’s why we’re focused on introducing more biosimilars over the coming years.” www.napp.co.uk

ALMOST A CENTURY OF EXPERTISE “Partnership working is central to what we do. Napp Pharmaceuticals has been working closely with the NHS since its inception. In addition to strong partnerships at all levels of the NHS, we work with policy-makers, trade associations and partners across the healthcare and pharmaceutical sectors. We know how to navigate its complexities and we’ve shaped our structure to its unique needs, so as the NHS changes, we can too.

“We foster a flexible culture at Napp where our people thrive on the ability to be agile and autonomous in response to the needs of our partners. What speaks volumes about the company is the low turnover of staff, as people stay with us for the long term. Few biosimilars teams in the industry have a team that’s stayed as one unit for so long, providing stability for our customers and meaning our decades of experience informs every project.”

Date of preparation: September 2019 UK/CORP-19032

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rheumatology drugs study Researchers at the Royal National Hospital for Rheumatic Diseases (RNHRD) in Bath, part of the Royal United Hospitals Bath NHS Foundation Trust, are celebrating recruiting the first patient globally to an international study that is investigating a treatment that could save the NHS hundreds of millions of pounds a year and benefit patients worldwide.

The study is researching the introduction of a cheaper biosimilar medicine for inflammatory and autoimmune diseases such as rheumatoid arthritis and axial spondyloarthritis. If successful it will enhance the understanding of the use of biosimilars in clinical practice.

Biosimilar medicines are the clinical equivalent of a branded biologic or originator medicine, which are expensive and can cost the NHS several thousand pounds a year to treat a single patient. Biosimilars can be produced once the patent for the original biologic medication expires.

Dr Raj Sengupta, Consultant Rheumatologist leading the study at the RNHRD, said: “Recruiting the first global patient to this study is a huge achievement and a testament to all the hard work and collaborative efforts of our research and database team.

“Biosimilars are now well-stablished for use in patients with inflammatory arthritis. Randomised controlled trials have demonstrated excellent efficacy for patients

who switch from the originator drug to the biosimilar.

There are however very few studies that have looked at real world evidence – data collected during an observational study – to demonstrate the efficacy of these switches. We are very proud to participate in this global study looking at the effectiveness of switching axial spondyloarthritis and psoriatic arthritis patients from Humira, the originator medicine, to Imraldi, the biosimilar in a real world setting.”

The Pan-EU Real-World Experience with Imraldi: ‘PROPER’ Research Study is designed to recruit approximately 1,200 to 1,400 patients from 60-70 EU centres, across a range of immune-driven inflammatory diseases – Rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, Crohn’s disease and ulcerative colitis.

PROPER is an observational study which follows the patient experience over 48 weeks after they have been switched from being treated with Humira to Imraldi.

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| BIOSCIENCE TODAY |

| r&d tax relief |

Research and Development Tax Relief– Updated HMRC Guidance for Software & IT Projects We’ve teamed up with Annette Beresford from Jurit LLP, who have recently been awarded ‘Most Pragmatic Legal Solutions Provide 2019’ in the UK Enterprise Awards, to write this article as we share a very similar client base.

Updated HMRC guidance on claiming Research and Development (R&D) Tax Relief for software and IT projects highlights the importance of considering the availability of R&D Tax Relief at the start of a project.

For companies operating in the technology sector, R&D Tax Relief can be one of the most valuable reliefs available. At current rates, a company that is a ‘small or medium-sized enterprise’ (SME) can qualify for tax relief at 230% of the qualifying revenue expenditure incurred in the relevant accounting period. Loss-making SMEs also have the option of surrendering some or all of the loss relating to qualifying R&D expenditure to HMRC in return for a R&D Tax Credit.

Larger companies that do not qualify as SMEs and also those SMEs that have been subcontracted to perform R&D, by either a large or international company, or who have received grant funding for their own project may instead be able to claim a R&D Expenditure Credit (RDEC), given ‘above the line’. This means that, instead of a superdeduction, a taxable credit is recognised as an additional “income” (currently at 12% of qualifying R&D expenditure), which is then set against certain tax liabilities of the company (in a prescribed order), with any remaining net credit being repaid to the company.

One of the trickier aspects of claiming the relief has always been identifying (and evidencing) qualifying R&D expenditure. The expenditure must relate to “research and development”, as defined by reference to the relevant accounting standards, subject to modifications set out in R&D guidelines maintained on the Department for Business, Energy and Industrial Strategy (BEIS) website.

What technological advance is the project seeking to achieve / what technological uncertainty is the project seeking to resolve?

Will there be an overall advance in technology (and not merely an extension to the relevant company’s own knowledge)?

Is an approach to resolving the relevant technological uncertainty already known and publicly available or “readily deducible (as judged by a competent professional working in the field), in which case R&D Tax Relief would not be available?

At what point will the relevant technological uncertainty be considered to have been “resolved”, so that subsequent activities would no longer qualify?

For expenditure on a given project to qualify for R&D Tax Relief, it is a prerequisite that the project represents an advance in science or technology and that the activities to which the expenditure relates contribute to such advance through the resolution of scientific or technological uncertainty. In addition, there are detailed rules on the types of R&D expenditure that can qualify (such as, among other things, the cost of qualifying staff involved, agency workers engaged, consumable stores used and software licence fees).

It is clear from the case studies that the devil is in the detail and that companies intending to claim will do well to consider at the start of a project to what extent expenditure will be “qualifying R&D expenditure”, and to identify ‘grey zones’ and potential difficulties at that point. This will allow work streams to be structured so as to facilitate demonstrating that relevant qualifying activities have been performed.

With regard to demonstrating eligible activity for software and Information Technology projects, HMRC has recently published updated guidance, including some case studies which aim to show how companies might consider whether they are eligible for making a claim. The case studies (available at www.gov.uk/hmrc-internal-manuals/ corporate-intangibles-research-and-developmentmanual/cird81980) are intended to be examples of how similar companies might identify the boundaries of R&D.

Please note that this information is of a general nature and should not be considered or relied on as legal or tax advice.

If you have any specific questions concerning this updated guidance or any other aspects of R&D Tax Relief, please reach out to a member of the Jurit LLP tax team (e-mail: info@jurit.com or dial 020 7846 2370) or to Simon Bulteel at Cooden Tax Consulting (e-mail info@coodentaxconsulting.co.uk or dial 01424 225345), quoting BioScience Today Magazine.

Relevant points which feature in the case studies include the following: Are the relevant R&D activities part of a wider project and, if so, where are the boundaries between R&D and other activities?

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Life Science success Whilst the recent past has been one of huge uncertainty with regards to the political and economic landscape across the globe, the past year saw major success in Life Sciences & Healthcare across the Eastern region.

Tony Jones

CEO, One Nucleus Record levels of venture investment, corporate deals, property investment and product development success suggest Life Sciences and Medical Technology research institutions and businesses are thriving. There remain concerns and challenges in maintaining this momentum absolutely, but when one considers factors such as: the strengths that have led to a track record of success; the changes within biomedical research driven by technology and demographics; and increasing collaborative spirit across local government boundaries, then the reasons to be optimistic are manifold.

The region has been at the forefront of emerging fields such as Precision Medicine, Genomics, Artificial Intelligence & Machine Learning, Advanced Manufacturing, Nutrition & Wellbeing and Medical Robotics as they have emerged from academic theory to practical application. These fields and disciplines are increasingly converging as we seek to not only develop new medicines, but to engage in ever earlier diagnoses for example. Harnessing the power of advances in areas such as genomics, electronic health records and imaging requires integration of vast pools of data, effective data science strategies and a modern NHS infrastructure. There is always room for improvement, but looking at NHS beacons such as Addenbrookes, Papworth and the Norfolk & Norwich University Hospital, all integrating with primary care across the region, then it is easy to see how the required data pools to enable evidencebased healthcare delivery are feasible.

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When one considers the source of inventions and insight that continue to challenge the status quo in disease understanding and treatment, then much like the clinical centres of excellence, one doesn’t travel far between world class research institutions. Commitment to investing in critical research base initiatives such as the Quadram Institute, Wellcome Genome Campus and Babraham Research Campus has rendered the region one of the hottest locations for academic research. The Centre for Advanced Manufacturing together with major stakeholders such as Hethel Innovation, TWI and BT of course enable the engineering into the sector to strengthen the offer considerably. Norwich Research Park continues to develop as a hub to attract entrepreneurs, investors and corporate partners engaged in forming and growing new businesses that are translating this excellent science into new products and services to benefit patients.

It is not all about new medicines and devices. Much is spoken and written about what emerging challenges such as changing demographics, costs of healthcare and antimicrobial resistance mean for future health and wellbeing.

Our region is primed to play a leading role on these aspects much like it has in the past centuries of addressing vital challenges. A key demographic shift is the ageing population. Through better nutrition, medicines and living standards, we are living longer. Ultimately, it is not simply life-span that we need to consider perhaps, but health-span if citizens are to have as good a quality of life throughout as possible.

Technology is changing faster than at any time in history.

Wearable technology for example, is facilitating the collection of ever more comprehensive data on health ď‚Š page 36

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 from page 35 status, disease monitoring and adherence to prescribed medications. Never has the biopharma industry had access to such Real World Data. Data in itself is not the key however, it is what can be done with the data that is important in order to provide knowledge and evidence. The increased Real World Evidence doesn’t just apply to humans.

Surveillance technology to monitor the spread of pathogens and microbiome studies to explore the relationship between a person and their gut flora are two areas that complement medical research and contribute to our understanding of what creates and maintains a suitable ecosystem to enable wellbeing. Much the same can be said of advances in agricultural technology and the food supply chain. Greater traceability, improved food standards and yield as well as environmentally sustainable production methods all have a potentially major impact on health and wellbeing. Research excellence in these areas via centres such as the Earlham Institute and John Innes Centre adds to the region’s power to investigate, inform and influence how we balance health, environment and economics in the future.

Exerting the potential influence and economic impact of these different but complementary research fields is in no small way enabled by the region’s ability to attract and retain suitably world class talent in the non-scientific disciplines such as entrepreneurship, finance, patents and legal. The highly developed ecosystem for translating science into business is a key factor in ensuring advances reach their market. Sustained government investment in research excellence and its infrastructure is vital if the region is to continue to lead, attracting the best possible talent across all required disciplines. Anything that suggests not investing in the ‘brand leader’ perhaps should be approached with caution.

The region is also fortunate to have a series of long-standing and collaborative industry networks such as One Nucleus, Cambridge Network, CW, AgriTech East and Cambridge CleanTech. These organisations, usually funded by member subscription rather than public money, can be effective conduits to the emerging regional government

| BIOSCIENCE TODAY |

created initiatives such as the UK Innovation Corridor and Cambridge Norwich Tech Corridor that aim to bring local boroughs and councils together in order to join the regional dots. The interdisciplinary requirement in future success, the need for scale and the need to accommodate growth suggest such cross-regional coordination must be beneficial. If not to attract businesses into the connecting spaces in the short to medium term, the connectivity, infrastructure and potential to create suitable commuting possibilities for those attracted to work in the existing centres of excellence is a very practical and necessary achievement if we are not to stifle success in the region.

A sign of others confidence in our region are the major investments and corporate deals into businesses here. There has been well in excess of £1Bn of private capital poured into the region over the past year and a half. Whether collaborations such as Microbiotica’s with Genentech, Mission Therapeutics with Abbvie and Crecsendo Biologics with Takeda or the significant financing events by CMR Surgical, Artios, Acacia Therapeutics or Nasdaq IPO’s by e.g. Bicycle Therapeutics, there are numerous signs of the maturing asset and company pipeline in the cluster. This in turn has driven confidence in real estate players also where we have seen very exciting investments from UK, USA, Asia and Europe into science parks and facilities.

Discovering new medicines and devices, changing behaviour to improve public health and aligning local competitor regions for a greater good has always been challenging. Persistence, creativity and dealing with regulatory change are common characteristics among researchers, entrepreneurs and their investors. It is now encouraging to see such characteristics in our local government bodies and policy makers. A coming together of such attitudes, desire and common vision across public and private sectors perhaps indicates the future is very bright for the East of England, UK. It will be an exhilarating journey to a part of! www.onenucleus.com

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| life sciences |

It is not all about new medicines and devices.

Much is spoken and written about what emerging challenges such as changing demographics, costs of healthcare and anti-microbial resistance mean for future health and wellbeing. Our region is primed to play a leading role on these aspects much like it has in the past centuries of addressing vital challenges.

TONY JONES CEO, ONE NUCLEUS

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Lab of the Future Congress An international congress bringing together leading pharmaceutical companies, research institutes and service providers to drive collaboration and innovation in the life sciences Open Pharma Research, has announced the launch of an international congress: the Lab of the Future Congress. This major gathering will take place on the 13-14th of November 2019 at the Wellcome Genome Campus in Cambridge, UK. Bringing together a range of high-profile speakers, the Lab of the Future was set up to provide access to the people and resources for life science companies to continue thriving in a rapidly-evolving world. The event is supported by The Pistoia Alliance, the global, not-for-profit members’ life science organisation working to lower barriers to innovation in R&D through pre-competitive collaboration (www. pistoiaalliance.org).

Key events will include a plenary session on the changing R&D landscape, and a panel on the role of technology as an enabler. Over 80 speakers have been selected to participate, including: Bryn Roberts, Global Head of Operations, Research & Early Development, Roche.

Monika Lessl, VP Head of Corporate Innovation and R&D, Bayer.

Veronique Birault, Head of Translational Medicine, Francis Crick Institute.

Steve Martin, Head of Biopharm Discovery R&D, GlaxoSmithKline.

Ian Churcher, Senior VP, Drug Discovery, BenevolentAI.

In addition to these talks, a major exhibition will showcase the work from the key service companies in this space. The conference centre boasts a unique open-plan design, which will encourage the anticipated 250-300 delegates to engage in open conversations.

Sponsors of the Congress to date include: Accenture, Thermo Fisher Scientific, CBRE, ZONTAL, Dassault Systèmes, Dotmatics, Avantor, Riffyn, SciBite, Synthace, ACD/Labs, Agilent, Digital Lab Consulting and L7 Informatics.

For a full programme, please visit: www.lab-of-the-future.com

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| diagnostic devices |

| BIOSCIENCE TODAY |

Diagnostic devices reimagined Diagnostic devices are coming on in leaps and bounds but you may be surprised to learn that one device that’s remained much the same since the late 1950s is the colonoscope. One researcher working to transform colonoscopies is Professor Pietro Valdastri, Chair in Robotics & Autonomous Systems at the University of Leeds.

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| diagnostic devices |

“Colon cancer is one of the deadliest forms of cancer, detected in the very early stages, 95% of people diagnosed survive for more than five years. Conversely, once the disease is showing symptoms, the likelihood of survival after five years is just 5%, so early diagnosis is crucial.

“Detecting colon cancer in its early stages is difficult and that’s where colonoscopies help, by inspecting the colon and potentially finding signs of the disease early, so over one million people are referred for a colonoscopy in the UK each year.”

COLONOSCOPY CHALLENGES “Colonoscopies are an invasive procedure that can be painful, so much so that in the US patients are given a general anaesthesia, whilst in the UK we use a mild sedative.

Faecal blood tests are also used to detect colon cancer and although they are less invasive, they are a less powerful diagnostic tool in this instance.

“Although the vision module used in colonoscopies has been updated over the years, the procedure itself hasn’t changed much since 1957, it still involves a rather rigid tube measuring about 1.5 metres being inserted and pushed up inside of the large intestine. It’s a difficult procedure, pain is a big problem and one in ten colonoscopies are not completed.

“Colonoscopes are difficult to use, requiring a lot of training, there is a shortage of trained gastroenterologists, which means waiting lists are long, much longer than the NHS target.

Our work is all about making colonoscopies painless and easier to carry out so waiting lists can be reduced.”

HARNESSING MAGNETIC MANIPULATION

Prof Valdastri and team

“Colonoscopes are difficult to use, requiring a lot of training, there is a shortage of trained gastroenterologists, which means waiting lists are long, much longer than the NHS target. Our work is all about making colonoscopies painless and easier to carry out so waiting lists can be reduced.”

When time is of the essence in both diagnosing and treating colon cancer this is an important step forward.”

SONOPILL SUCCESS Funded by a five-year EPSRC programme grant, ‘Sonopill’ has been developed by a consortium of researchers based across four institutions, Glasgow, Leeds, Dundee and Herriot Watt. The lead researcher on the project is Sandy Cochran, Professor of Ultrasound Materials and Systems at the University of Glasgow.

“With an increasing demand for colonoscopies, it is more important than ever to be able to deliver a precise, targeted, and cost-effective treatment that is comfortable for patients,” explains Professor Sandy Cochran. “We are one step closer to delivering that.

“Our solution is to employ magnetic manipulation. A robotic arm, fitted with a magnet, will gently manoeuvre a tiny robotic capsule (fitted with a magnet) through the colon, thus avoiding the pushing, snagging and discomfort traditionally associated with colonoscopies.

“We hope that in the near future, the ‘Sonopill’ will be available to all patients as part of regular medical check-ups, effectively catching serious diseases at an early stage and monitoring the health of everyone’s digestive system.”

“The magnetic forces used are harmless and can pass through human tissue, doing away with the need for a physical connection between the robotic arm and the capsule. The robotic capsule is also much thinner and extremely flexible when compared to traditional colonoscopes, helping to reduce discomfort.

TRANSFORMING COLONOSCOPIES

“The capsule can be changed depending on the procedure.

My research team, in collaboration with the University of Glasgow, has developed a capsule that can capture microultrasound images.

“An artificial intelligence system (AI) ensures the capsule can position itself correctly against the gut wall to get the best quality images. A feasibility study has shown that if the capsule get dislodged, the AI system can navigate it back to the required location.”

MICRO-ULTRASOUND TECHNOLOGY The tiny robotic capsule or ‘Sonopill’ which incorporates micro-ultrasound technology, has the potential to change the way doctors conduct examinations of the gastrointestinal tract. ‘Sonopill’ can power itself, undertake precise movements as well as collect and communicate data.

“Previous studies have shown that micro-ultrasound can capture high-resolution images and visualise small lesions in the superficial layers of the gut,” explains Professor Valdastri, “making it better able to identify some types of cell change associated with cancer and provide valuable information about the early signs of disease.

“Mirco-ultrasound would provide in situ diagnostic, preventing the need for getting samples of tissue and sending them to the lab” explains Professor Valdastri, “enabling malignant tissues to be identified on the spot.

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All in all, the reimagined colonoscopy, incorporating ‘Sonopill’ technology, has the potential to transform how the large intestine is examined, providing benefits for patients and clinicians alike.

“The procedure will be much less painful for patients and easier to carry out, requiring less training, so waiting lists can come down more quickly,” explains Professor Valdastri.

“Given time is of the essence in diagnosing and treating colon cancer, increasing access to colonoscopies and reducing waiting times is central to saving lives.

“Our device is less expensive to produce than a traditional colonoscope, it is also disposable, thereby reducing cleaning and maintenance costs too, which also helps the NHS and assists in building a business case for the new device.

“Cancer Research UK has funded the colonoscopy project and we aim to carry out the first human trial in November 2020. The technology also has the potential to be applied to other areas like diagnosing throat or stomach problems.”

INTO THE FUTURE “Looking to the future, it’s possible the technology will have more applications. We’re working on a project supported by the European Research Council to miniaturise the technology further so it can be used in the bronchial tree of the lungs, in the bloodstream or to perform neurosurgery, potentially allowing access to deep lesions.

“Treating deep brain tumours and haemorrhages without causing disruption is a challenge. By creating flexible instruments that can move around sensitive areas of the brain, we hope to make accessing the brain possible without causing trauma – this is our blue-sky research.”

| intellectual property |

| BIOSCIENCE TODAY |

How to protect your IP rights in Europe Intellectual property rights are territorial rights, meaning that the protection afforded by a granted patent or a registered trademark is geographically limited.

Many companies that protect their inventions, brands or product designs in their home country, do not realise that this does not give them automatic protection in other countries.

Unfortunately, this means that many businesses don’t get protection for their brands and/or technology in other (commercially important) countries.

Jim Robertson

Regardless of whether you are interested in seeking patent protection for a new invention, trademark protection for a product name/logo or registered design protection for the appearance of a product, you will need to protect your rights both at home and abroad.

With this in mind, here are some key considerations for how to protect your IP rights in Europe.

RESEARCH THE MARKET Whilst you may have IP rights in one country, in other countries there may be brands or products which have registered IP that could be used to stop you from trading there.

For trademarks, perform a search to check to see whether your brand has already been registered in countries you want to commercialise in.

For inventions, if you have already filed a patent application in one territory, such as the UK, check the deadline by which you must file the patent application in other territories.

This is a year from the date of first filing. Also, get the patent office to do a search on your patent application to see what other relevant technology is out there. This can take several months, so ensure that the search request is submitted as soon as possible.

To avoid a costly lawsuit, make sure you research the market and its IP Registers to ensure your brands and products will not infringe on other companies’ rights.

THINK STRATEGICALLY AND REVIEW REGULARLY Companies should ensure that they apply for patent protection for their inventions in all territories which will be commercially relevant to them.

The potential monopoly provided by patent protection is the only effective way to prevent others from exploiting your inventions and receiving a good return on the initial investment.

Equally, it is extremely important for biosciences companies to protect their brands with registered trademarks. When a granted patent expires, brand names (e.g. Nurofen®) are crucial in maintaining a competitive edge over generic manufacturers when the market may become diluted.

If you do not take action to protect your rights, it can be the case that unscrupulous third parties will apply to register it themselves. If that happens, it can be extremely costly and difficult to resolve the problems.

You also need to remember that as your business develops and grows, your IP requirements may change as a result. You should regularly review your IP protection to ensure it fits in with your ongoing business goals and strategy.

REMEMBER R&D TAX CREDITS AND PATENT BOX The UK government has an excellent R&D tax credit scheme which reimburses innovators for their R&D expenditure

- talk to your advisors to see how you can take advantage of this. Similarly, there is also a “Patent Box” scheme that reduces the corporate tax rate on profits from patented technology (and this can be internal processes as well as products that you can sell to customers). It can, for example, be worth getting a narrow UK patent granted quickly which is focused on a specific product/method and for the sole purpose of the Patent Box scheme whilst also seeking much broader patents with the aim of obtaining a commercial monopoly over the broader technology and innovation.

REGIONAL PATENTS To help encourage cost efficiency, countries in various parts of the world have formed regional patent systems.

The European Patent Convention is one example, and allows you to obtain a single European patent, giving you access to protection in almost 40 European countries, plus an increasing number of other non-European states that are cooperating with the European Patent Office. Once a European patent has been granted, it can be brought into force in the individual countries that you want the patent to have effect. The European patent will then have the same effect (and be subject to the same conditions as) a national patent granted in that country.

BE AWARE OF TIMESCALES Obtaining a patent can be an altogether more difficult and lengthy process than registering a trademark or a design.

It is difficult to put a number to the duration of the patent application process as it varies hugely depending on the territory in which you have applied for the patent and also depending on the subject-matter of the patent application and the invention disclosed.

Assuming that the invention is patentable, in Europe, the application process can take a couple of years. It is also not unheard of for patent applications to take a lot longer than this to proceed to grant. However, it is also possible to speed things up significantly by working with the examiner and the system by being proactive with prosecution, waiving unnecessary periods where the patent application is effectively on hold, and requesting acceleration, and having telephone interviews with examiners.

BE MINDFUL OF THE IMPACT OF BREXIT The first thing to say is that there is nothing to worry about with patents. European patents are governed by the European Patent Convention which is nothing to do with the EU. Therefore, they are not affected at all by Brexit.

Trademarks and designs are another matter, however. EU trademarks and EU designs are both governed by EU law, and so will be affected by Brexit.

As things stand, UK attorneys and lawyers will not in general be entitled to handle EU trademark and design matters after 29th March 2019.

However, by virtue of its membership of the AIPEX European Alliance, Wynne-Jones IP is uniquely positioned to continue to handle EU work.

Brexit presents challenges for many thousands of UK businesses, some of whom haven’t even realised it yet. But, with access to an IP pan-European law firm with expertise in all sectors across all EU states, they can turn that challenge into an opportunity. www.wynne-jones.com

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Your team for Life Sciences IP Is Life Sciences your field?

When you need help with intellectual property rights, remember that we’ve been active in this field for decades.

Whether you’re a lone inventor, SME or large corporation, you must identify and protect your Crown Jewels®. These are the core technologies, inventions or processes that are critical to your business strategy.

We will work with you to fully understand the commercial and strategic needs of your business and take away the hassle and worry of IP.

We know our stuff in: Bio-sensors | Diagnostics | Assays | Pharmaceuticals and Drug Synthesis | Small Molecules | Plant Breeders’ Rights | Cosmetics | Supplementary Protection Certificates | Vaccines | Biochemistry | Microbiology | Pharmacology | Biocides | Healthcare Sciences | Proteomics | Biophysics | Veterinary Medicines | Medical Devices

What’s more we know our stuff in: Strategic IP management | Setting IP budgets | IP asset management | Funding for IP

What are you waiting for?

Let’s talk Life Sciences.

Jim Robertson, Life Sciences Team Leader T: 01242 267 600 E: jim.robertson@wynne-jones.com W: www.wynne-jones.com

| intellectual property |

| BIOSCIENCE TODAY |

Drug delivery Drug delivery encompasses a raft of issues that require real world solutions for the efficacy of drugs to be realised in the cell. The localisation of drugs, to particular compartments or tissues, can facilitate improvements in efficacy, safety, activity and the desired responses that result, and tailor the duration of activity. So, there is a clear prospect of reward for any group able to improve selectivity by targeting specific compartments but, especially for biologics, there are significant challenges.

Dr Jason Bellia

Senior Patent Examiner at the UK Intellectual Property Office (IPO) I will look at just two of a vast number of routes - one to deliver nucleic acids across cell membranes and another looking to harness paracellular absorption to deliver biologics, for example across the GI tract. These solutions representing different ways to reap some of these rewards and illustrate a little about the patent system along the way.

Of the inventions that pass through our hands at the IPO many represent incremental improvements. In these cases we are often left with the question “is the increment enough to be new and inventive?” – not merely a modification that would be obvious to someone working in that field. Truly disruptive technology is often only really clear in hindsight, but a clear idea of the problem to be solved and the context provided by the present, presumably imperfect solutions, is always necessary whatever the invention.

The challenge of getting biologics across membranes doesn’t even start with the polar phospholipid groups - “Cells are not simple lipid bilayers, everyone draws these, but mother nature never gets the memo!” so said Prof Mrsny from the University of Bath - I have drawn on heavily his lecture for this article. The classical picture of the passive, stationary lipid bilayer with the odd receptor is far from the truth. The so called “glycocalyx” for example as found lining luminal endothelial cells in vascular tissues, comprises a complex array of anionic molecules which are variously recruited as coreceptors and involved in cell to cell interactions. These molecules present a challenge for avoiding off-target effects, even before biologics reach the lipid bi-layer.

Cell penetrating peptides especially those displaying highly basic sequences often come with problems of permanently disrupting the cell membrane, the classic alternative is the use of viral particles, or indirectly influencing the cell via cell surface receptors.

Nucleic acid-based drugs acutely illustrate these problems.

While gene therapy has for decades held out the prospect of treating a vast number of diseases the challenge of delivery has inhibited the growth of this field. At present approximately 70% of gene therapy trials employ viral

vectors, even though they generally suffer from the limitations of immune response activation, tropism (or selectivity of viruses for particular tissues/hosts), limited capacity and complexity of production, and even the risk of carcinogenesis.

Non-viral vectors don’t generally suffer from these problems but are yet to achieve anything like the efficiency of transfection achieved by viruses. One proposed solution has been the system developed by Alnylam Pharmaceuticals, concerning the delivery of RNA interference molecules using a delivery mechanism targeted for hepatocytes wherein the nucleic acid is conjugated to a N-acetylD-Galactosylamine (GalNac) molecule. In vivo GalNac binds to the sialoglycoprotein receptor ASGP-R targeted for its high capacity and abundance on hepatocytes.

The affinity of the receptor for the GalNac bound nucleic acid is further enhanced to the nM range by providing a conjugate with a trivalent cluster of GalNac sugars, with subsequent degradation of the trivalent cluster in the low pH of the endosome. Liberation of the siRNA intact from the endosome may however require the separate use of fusogenic agents to disrupt the endosome, enabling liberation of the conjugate to the cytoplasm, where it can suppress transcription.

Fusogenic agents come with associated problems. Indeed “endosome escape” - liberating active agents from the endocytic pathway before the endosome matures into an ultimately destructive lysosome, is a perennial problem of drug delivery to cells. One proposed method provides biomolecules with an early exit from the endosomal pathway by the use of endosomal escape domains, initial studies on GFP internalisation by carcinoma cells have shown that conjugating a bioactive with an “endosomal escape domain” comprising a combination of indole and phenyl groups a fixed distance of 6 PEG units from the cargo can favour delivering the cargo to the cytoplasm before destroying its contents.

An alternative to the passage of compounds into (and through) cells when seeking intestinal absorption, is the paracellular route, as has been investigated by Professor Mrsny at Bath University. Navigating the paracellular route, between the cells of the intestinal epithelium can accommodate the passage of materials as large as 100nm in diameter and provides a very large potential surface

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| BIOSCIENCE TODAY |

| intellectual property |

area for absorption. One method developed has been to trigger an endogenous mechanism for enhancing tight junction permeability of intestinal epithelia. This operates by promoting cytoskeletal contraction triggered in the presence of inert macromolecule nutrients, this route has the benefit of being readily reversible. The phosphorylation of Myosin light chain (MLC) by its kinase results in a conformational change in the structure of myosin II in enterocytes increasing tight junction permeability, whilst an endogenous MLC phosphatase in due course reverses the effect, closing the tight junction.

Rationally designed peptides termed permeant inhibitor of phosphatases (PIPs) block this dephosphorylation step to keep the tight junctions open for longer in the presence of macromolecular nutrients, and so when administered with the biomolecular drug of choice enable a temporary passage between enterocytes in the gut.

All in all, biologics face challenges at every interface within the patient, but this protective complexity is probably just what mother nature intended.

Comparing the journal references and the patents for the papers on endosome escape and paracellular absorption it is notable that they illustrate a number of differences of patents vs journal publications that underlie their different purposes. The journals, as we would expect, focus on testing the optimised molecules to illustrate the particular effects they produce in vivo and demonstrate the validity of the conclusions drawn. The patents, on the other hand, use largely the same experimental data but extrapolate from the optimised molecules from the

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literature references to propose alternative molecules that demonstrate the same effects, and it is this class of molecules that are defined in the patent claims. The inventors are seeking to maximise the commercial benefit of their invention by casting the scope of the protection afforded by the patent widely. This difference can be a useful adjunct in literature research to see where the proposed boundaries of the effects may lie, and what elements of the molecule the inventors see as crucial.

It is also worth noting that the patents have a priority date (when the first version of the disclosure was submitted to a patent office) several years before the journal publication date and as such the patents were presumably submitted long before of the journal articles. The above inventors have wisely submitted their patent applications before the journal article to avoid making an invention publicly available and, as such, preventing its protection by a patent. It is disappointing for patent examiners to see that this basic message hasn’t always got through to the research community.

Intellectual Property Office is an operating name of the Patent Office

| intellectual property |

| BIOSCIENCE TODAY |

The SPC manufacturing waiver: curtailing protection or boosting competition?

Lucy O’Brien

Trainee Patent Attorney, A. A. Thornton & Co. Supplementary Protection Certificates (SPCs) are a valuable IP asset to most major life science businesses. The ability to extend the term of a patent relating to a particular medicinal or plant protection product beyond its twenty years, up to an additional five years, provides an essential compensation period for patent owners to offset any delays in the time taken to obtain marketing authorisation for the product in question. For important commercial products this additional period of market exclusivity is critical to recoup research and development costs.

However, recent changes to the EU regulation governing SPCs could have a major impact on the advantages of this extension in Europe.

On 1 July 2019, Regulation (EU) 2019/933 entered into force, commonly known as the SPC manufacturing waiver.

WHAT IS THE SPC MANUFACTURING WAIVER? The SPC manufacturing waiver provides an exemption for EU-based companies to manufacture a generic or biosimilar version of an SPC protected drug exclusively for exporting outside of the EEA and into a territory where the patent protection for the drug does not exist or has expired.

The waiver will only apply during the last six months of the SPC term. As well as allowing European based generics and biosimilar manufacturers to establish a market outside of the EU before expiry of the SPC, it also allows for them to begin stockpiling a product and then launch in the EEA on the day after expiry of the SPC. In order to try and provide more certainty to the SPC proprietor, the manufacturer must inform the SPC proprietor and the national patent office three months prior to the first related act with information on who they are and where the export and/or stockpiling will take place. Currently, the waiver affects any SPC application filed on or after 1 July 2019. However, after a three year transition period, on 2 July 2022, this change will also affect any SPC application which had been filed but was not yet in force on 1 July 2019.

As SPCs are national rights, they are applied for on an individual country basis. The UK IPO have confirmed that UK manufacturers will benefit from the waiver rights, even in the case of a “no deal” Brexit. However, changes will be necessary to account for the fact that the EU legislation makes specific references to the EU market.

WHAT ARE THE POTENTIAL PROBLEMS? The intention of creating such a waiver is to prevent generic and biosimilar manufactures from moving out of the EU and to allow them to compete with other manufacturers outside of the EU. Such a change will have a noticeable impact on SPC owners, as well as increase the competition to become the first generic on the market.

A number of EU states have raised concerns regarding the waiver, including Denmark, Czech Republic, Belgium, France and Spain. Denmark considers that a re-balance is required to prevent “undermining the strong competitive position of the EU established innovative pharmaceutical industry”, whilst the Czech Republic raised concerns that “Europe might lose its attractiveness as a centre of research and development, which might have a negative impact in particular on EU patients who are dependent on the supply of innovative medicinal products”.

The European Commission will review the effect of this waiver in July 2024, and every five years afterwards, in order to establish whether the intended benefits have been achieved. However, it is likely that patent proprietors that rely not only on the additional SPC term for protection, but also the delay from EU-based generics and biosimilar manufacturers reaching the market, will feel the effects much sooner than the five year review date.

If you have queries regarding this topic, or other pharmaceutical or biotechnological matters, please contact Lucy O’Brien at lco@aathornton.com or visit our website www.aathornton.com

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| BIOSCIENCE TODAY |

| news |

Targetting fast-growing cancer cells

The discovery that an essential protein plays a protective role during cell division, could open the door to better targeted treatment of fast-growing cancer cells.

Polo-like kinase (PLK1) was previously thought to have a major function – helping chromosome alignment during mitosis for cell division. But scientists at the Genome Damage and Stability Centre (GDSC) at the University of Sussex, have found that it also plays a crucial protective role, guarding against severe DNA damage caused during mitosis in cultured human cells.

It casts doubts over theories that by inhibiting PLK1, fastgrowing cancerous cells could be stopped from dividing and replicating, suggesting that this technique needs further research to avoid damaging side effects.

Dr Kok-Lung Chan, Wellcome Trust and Royal Society Sir Henry Dale Fellow at the GDSC said: “Up until now, scientists thought that one of the key roles of PLK1 was to help chromosomes to be stably captured for partition during mitosis.

“So it was thought that if that protein was inhibited or lacking, the duplicated chromosomes couldn’t be grasped properly and, in the case of cancerous cells, wouldn’t be able to segregate equally.

“We’ve discovered that PLK1 actually has a crucial protective role and is needed to avoid ruptures and splits of chromosomes, of which inhibition could have dangerous side effects on otherwise healthy growing cells.”

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The new findings, published in Nature Communications, suggest that any interference with the function of this essential protein could remove a protective barrier, resulting in specific DNA damage and chromosome rearrangements.

Dr Chan said: “For the first time, we have found that PLK1 works to maintain the rigidity of a critical part of the chromosome called the centromere. When the protein is lacking, centromeres become very fragile and rupture during cell division, causing ‘whole chromosome arm splitting’.

“Effectively, this means that, when they divide, chromosome arms are split in the wrong place. In principle, they can rearrange themselves resulting in characteristic whole-arm rearrangements, which are commonly observed in cancers and were also reported in some genetic disorders like Downs Syndrome.”

Interestingly, Dr Chan believes that the identification of the new role played by PLK1 could help clinicians develop cancer treatments which better target fast growing cells by not just blocking their division but also by simultaneously damaging their chromosome integrity.

Dr Chan explained: “Further investigation on this new function might actually help us to understand how the PLK1 inhibitors kill cancerous cells and could potentially improve future cancer therapies.”

| training and education |

| BIOSCIENCE TODAY |

The hidden way to fill vacancies, train and retain The BSc (Hons) Biomedical Science (pathology lab based) degree apprenticeship has been developed through consultation with pathology laboratory employers and is co-delivered, meeting the requirements for a Healthcare Science Practitioner (Biomedical Scientist) apprenticeship.

The programme has expanded rapidly over the past couple of years as the university has worked closely with employer partners to offer this industry-relevant programme and meet employer workforce development needs.

I am passionate about Salford and about increasing the opportunities for individuals across the region and apprenticeships are the perfect route for people to pursue a career across a number of different sectors.”

TRAIN AND RETAIN

Shane Rhodes, Apprentice Biomedical Scientist, Manchester Royal Infirmary

This alternative route to higher level qualifications can be accessed by your current employees or used as a tool to attract new talent to your business.

Develop and up-skill your workforce in a cost-effective way.

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Work around your commitments with flexible study options.

Deborah Seddon, Haematology and Blood Bank Manager, Salford Royal NHS Foundation Trust “We are currently supporting an employee through the BSc (Hons) Biomedical Science apprenticeship programme at the University of Salford. The initial interest within the NHS in apprenticeships came from the impact the levy was having on our budget.

I really believe apprenticeships are the way forward for our career – being able to grow your own talent and nurture the individual along the way results in a more knowledgeable Biomedical Scientist at the end.

The apprentice will have the opportunity to encounter more situations with support before they start working alone. I also believe it is healthy to have employees on such training programmes in the department as it keeps everyone on their toes – we are all continually refreshing our knowledge of developments in the field.

“The Biomedical Science degree apprenticeship and my role within the haematology and transfusion lab at Manchester Royal Infirmary go hand in hand - the on the job learning in the workplace really helps to consolidate the knowledge and theory from the classroom. If you are looking to get into a career as a Biomedical Scientist, then it really is a no brainer to go down the apprenticeship route – the real-world experience in the lab makes you such an asset to the team right from day one.”

APPRENTICESHIP FUNDING The apprenticeship levy was introduced in April 2017 and requires all employers operating in the UK, with a pay bill of over £3 million each year to invest in apprenticeships.

The funding policy supports the changes to the way apprenticeships in England are paid for, underpinned by the apprenticeship levy of 0.5% of the annual pay bill for companies paying over £3 million per year.

There is also a co-investment model for companies who will not be paying into the levy. The government will cover 95% of the cost of the apprenticeship and the employer will only have to contribute the remaining 5%. Once payments have been declared to HMRC, employers will now have access to a digital apprenticeship account from which they will be able to access funding to pay for apprenticeship training.

There is also an opportunity for larger levy paying organisations to transfer up to 25% of their unspent levy funds to other, smaller employers to support their workforce development.

GET IN TOUCH NOW TO FIND OUT MORE: apprenticeships@salford.ac.uk 0161 295 4612

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CAN YOU

AFFORD

NOT TO? INVEST TO EMPOWER YOUR WORKFORCE A great way to attract and retain talent for your organisation, boost productivity and up-skill your workforce.

Our Healthcare Science Practitioner Degree Apprenticeship allows students to exit with a full BSc (Hons) Biomedical Science degree qualification. / Apprenticeship funding available / Delivered on a part-time, day-release basis / Increase retention by offering your workforce the chance to develop and progress / Tailor apprentices’ learning to your requirements Get in touch today to find out more: www.salford.ac.uk/apprenticeships apprenticeships@salford.ac.uk

DEGREE APPRENTICESHIPS

| news |

| BIOSCIENCE TODAY |

Wild geese take climate action Migratory animals are actively adjusting their traditions to climate change, new research has found.

An international team of researchers from the University of St Andrews, with Norwegian, Dutch and British colleagues, found that barnacle geese have shifted their migratory route within the last 25 years.

In research recently published in the journal Global Change Biology, the research team concluded that individual geese have decided to change to the new route, and that other geese now learn the new habit from each other.

Dr Thomas Oudman of the School of Biology at the University of St Andrews said: “It makes sense that the birds went even further North, because where snow used to be very common there at the time of their arrival in Norway, these days it is often freshly green there: the most nutritious stage.

“What surprised us is that it is mainly the young geese who have shifted. The youngsters are responding to a trend they could not have experienced during their short life.”

Adult geese are also increasingly shifting north, although they often return to the traditional area in their old age.

The study is among the first to provide hard evidence that wild animals are inventing new traditions to cope with climate change.

Dr Oudman added: “These patterns point at a complex social system, which enables the geese to rapidly colonise newly available areas.”

The migratory birds, who traditionally fuelled up (staged) just South of the Arctic circle in Norway on their journey from the UK to their breeding grounds on Svalbard, now mainly stage in northern Norway far above the Arctic circle.

Contrary to most other migratory birds, barnacle geese flourish even while their natural habitat is rapidly changing.

The conclusions are based on analysis of 45 years of observations by the Norwegian Institute for Nature Research, the University of St Andrews, the University of Groningen in the Netherlands, BirdLife Norway and the British Waterfowl and Wetlands Trust.

Barnacle geese are able to adapt to climate change due to the availability of alternative places with sufficient food at the right time, and without the threat of disturbance from humans or other dangerous animals.

The availability of alternative habitats may also help other animals to adapt to climate change. Animal species that are not so explorative and which are less sociable may take much longer to discover such places.

“It makes sense that the birds went even further North, because where snow used to be very common there at the time of their arrival in Norway, these days it is often freshly green there: the most nutritious stage. What surprised us is that it is mainly the young geese who have shifted. The youngsters are responding to a trend they could not have experienced during their short life.”

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Having a big audience is one thing, knowing how to engage them is another.

e: info@be-everywhere.co.uk t: 0191 5805 990 www.be-everywhere.co.uk

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