Bioscience Today 24

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Clinical trials • Disease • Laboratory technology • Innovation • Drug development and discovery

ISSUE24

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foreword Helen Compson Editor in chief

Editor Helen Compson helen.compson@distinctivegroup.co.uk

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TURNING THE SPOTLIGHT ON SOME OF THE WORLD CLASS RESEARCH ESTABLISHING NEW FRONTIERS IN THE TREATMENT OF DISEASE In a world first, scientists at the University of Sussex have deduced that low blood oxygen levels could explain why memory loss is an early symptom of Alzheimer’s.

They have recorded blood oxygen levels in the hippocampus and provided experimental proof for why the area, commonly referred to as the brain’s memory centre, is vulnerable to damage and degeneration, a precursor to the disease.

Dr Catherine Hall, senior lecturer in psychology, said: “If it’s right that increasing blood flow in the hippocampus is important in protecting the brain from diseases like Alzheimer’s, then it will throw further weight behind the importance of regular exercise and a low-cholesterol diet to long-term brain health.”

Our knowledge about treatment options for progressive multiple sclerosis will be advanced by the launch, later this year, of a groundbreaking mega-trial.

Distinctive Publishing or BioScience Today cannot be held responsible for any inaccuracies that may occur, individual products or services advertised or late entries. No part of this publication may be reproduced or scanned without prior written permission of the publishers and BioScience Today.

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Christened Octopus to reflect the multiple arms of research it will embody, the clinical trial is being described as ‘revolutionary’ in its approach to identifying and delivering desperately needed treatments much faster than ever before.

Dr Emma Gray, assistant director of research at the MS Society, said: “More than 130,000 people live with MS in the UK and there are tens of thousands with progressive forms who have nothing to stop their MS getting worse.

“But we believe we can stop MS, and the launch of Octopus is a crucial moment in our journey towards that goal.”

Meanwhile, biotechnology company Phico Therapeutics Ltd is developing engineered phage technology as the basis of a new generation of antibiotics to overcome antibacterial resistance.

Hot on the heels of a £13m grant awarded earlier this year, it has just announced another £7m in new investments, funds that will be used to develop its SASPject technology platform and taking its lead product to clinic.

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features

3D printed liver aids life saving surgery

18 14 UK ‘Octopus’ trial tackling multiple sclerosis is a world first Genome sequencing reveals how salmonella carves out a niche in pork production

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contents / www.biosciencetoday.co.uk / issue 24 /

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Foreword

4-5

Contents

7-13

NEWS

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intellectual property The Nagoya Protocol and the UK – Are you Compliant?

14-16

Clinical trials A ground breaking mega-trial for progressive multiple sclerosis will be launched in the UK later this year.

18-20

Disease Variants of concern (VOCs) and variants of interest (VOIs) have become familiar terms due to the current pandemic, but variants of familiar pathogens such as salmonella also present a threat to human and animal health.

22-25

Laboratory technology Surgeons will perform liver resections with greater accuracy and deliver improved patient outcomes thanks to new research by Nottingham Trent University. Senior research fellow Richard Arm has developed a way to 3D-print scan data of cancer-hit patient organs so that clinicians can rehearse difficult operations on lifelike models.

26-27

Innovation Innovation experts, KTN, publish roadmap calling for multi-million pound investment to develop and commercialise groundbreaking treatments for disorders of the brain and nervous system.

28-29

Drug development and discovery Two new forms of therapy give hope when blood cancer returns and bowel cancer spreads.

Combination immunotherapy for advanced bowel cancer approved for NHS in England.

26 A transformative roadmap for neurotechnology in the UK

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Blood oxygen levels could explain why memory loss is an early symptom of Alzheimer’s The findings demonstrate how the brain’s memory centre operates at a ‘watershed’ making it especially vulnerable to damage Study suggests increasing blood flow in the hippocampus might be really effective at preventing damage and memory loss Findings underline importance of exercise and a low-cholesterol diet in long-term brain health, by boosting blood vessel health and brain blood flow In a world first, scientists from the University of Sussex have recorded blood oxygen levels in the hippocampus and provided experimental proof for why the area, commonly referred to as ‘the brain’s memory centre’, is vulnerable to damage and degeneration, a precursor to Alzheimer’s disease.

To understand why this region is so sensitive, the University of Sussex researchers, headed up by Dr Catherine Hall from the School of Psychology and Sussex Neuroscience, studied brain activity and blood flow in the hippocampus of mice. The researchers then used simulations to predict that the amount of oxygen supplied to hippocampal neurons furthest from blood vessels is only just enough for the cells to keep working normally.

Dr Catherine Hall, Senior Lecturer in Psychology at the University of Sussex said: “These findings are an important step in the search for preventative measures and treatments for Alzheimer’s, because they suggest that increasing blood flow in the hippocampus might be really effective at preventing damage from happening.

“If it’s right that increasing blood flow in the hippocampus is important in protecting the brain from diseases like Alzheimer’s, then it will throw further weight behind the importance of regular exercise and a low-cholesterol diet to long-term brain health.

“We think that the hippocampus exists at a watershed.

It’s just about OK normally, but when anything else happens to decrease brain blood flow, oxygen levels in the hippocampus reduce to levels that stop neurons working.

We think that’s probably why Alzheimer’s disease first causes memory problems – because the early decrease in blood flow stops the hippocampus from working properly.

“The same factors that put you at risk of having a heart attack make you more likely to develop dementia. That’s

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because our brains need enough blood flow to provide energy – in the form of oxygen and glucose – so brain cells can work properly, and because blood flow can clear away waste products such as the beta amyloid proteins that build up in Alzheimer’s disease.

“Now we want to discover whether the lower blood flow and oxygen levels in the hippocampus are what causes beta amyloid to start to build up in Alzheimer’s disease. Understanding what causes early damage will be really important to help us learn how to treat or prevent disease.”

Dr Kira Shaw, a psychology researcher at the University of Sussex who undertook the main experiments, said: “We found that blood flow and oxygen levels in the hippocampus were lower than those in the visual cortex.

Also, when neurons are active, there is a large increase in blood flow and oxygen levels in the visual cortex.

This provides energy to hungry neurons. But in the hippocampus, these responses were much smaller.”

The scientists also found that blood vessels in the hippocampus contained fewer mRNA transcripts (codes for making proteins) for proteins that shape blood vessel dilation. Additionally, the cells that dilate small blood vessels, called pericytes, were a different shape in the hippocampus than in the visual cortex.

Dr Shaw concluded: “We think blood vessels in the hippocampus are less able to dilate than in the visual cortex”.

The full research paper, ‘Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences’ is published in Nature Communications. This research was funded by the Medical Research Council, the Academy of Medical Sciences, and the Wellcome Trust.

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New material to treat wounds can protect against resistant bacteria Researchers at Chalmers University of Technology, Sweden, have developed a new material that prevents infections in wounds – a specially designed hydrogel, that works against all types of bacteria, including antibioticresistant ones. The new material offers great hope for combating a growing global problem.

The World Health Organization describes antibioticresistant bacteria as one of the greatest threats to global health. To deal with the problem, there needs to be a shift in the way we use antibiotics, and new, sustainable medical technologies must be developed.

“After testing our new hydrogel on different types of bacteria, we observed a high level of effectiveness, including against those which have become resistant to antibiotics,” says Martin Andersson, research leader for the study and Professor at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology.

Research and development of the material has been ongoing for many years at Martin Andersson’s group at Chalmers, growing in scope along the way, with a particular focus on the possibilities for wound care. Now, the important results are published as a scientific article in the journal ACS Biomaterials Science & Engineering.

The main purpose of the studies so far has been to explore new medical technology solutions to help reduce the use of systemic antibiotics. Resistant bacteria cause what is referred to as hospital-acquired infection – a life-threatening condition that is increasing in incidence worldwide.

MIMICKING THE NATURAL IMMUNE SYSTEM The active substance in the new bactericidal material consists of antimicrobial peptides, small proteins which are found naturally in our immune system.

“With these types of peptides, there is a very low risk for bacteria to develop resistance against them, since they only affect the outermost membrane of the bacteria. That is

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perhaps the foremost reason why they are so interesting to work with,” says Martin Andersson.

Researchers have long tried to find ways to use these peptides in medical applications, but so far without much success. The problem is that they break down quickly when they come into contact with bodily fluids such as blood.

The current study describes how the researchers managed to overcome the problem through the development of a nanostructured hydrogel, into which the peptides are permanently bound, creating a protective environment.

“The material is very promising. It is harmless to the body’s own cells and gentle on the skin. In our measurements, the protective effect of the hydrogel on the antimicrobial peptides is clear– the peptides degrade much slower when they are bound to it,” says Edvin Blomstrand, Doctoral Student at the Department of Chemistry and Chemical Engineering at Chalmers, and one of the main authors of the article.

“We expected good results, but we were really positively surprised at quite how effective the material has proven,” adds Martin Andersson.

According to the researchers, this new material is the first medical device to make successful use of antimicrobial peptides in a clinically and commercially viable manner.

There are many varied and promising opportunities for clinical application.

STARTUP COMPANY AMFERIA TAKES THE RESEARCH FROM LAB TO MARKET In recent years, foundational research into the antimicrobial peptide hydrogel has run in parallel with commercial development of the innovation through the spin-off company Amferia AB. The company was founded in 2018

by Martin Andersson together with Saba Atefyekta and Anand Kumar Rajasekharan, who both defended their dissertations at Chalmers’ Department of Chemistry and Chemical Engineering. The material and the idea, which is currently developed as an antibacterial wound patch, has generated interest around the world, attracting significant investment and receiving several awards. The company is working intensively to get the material to market so that it can benefit wider society.

Before the new material can benefit hospitals and patients, clinical studies are needed, which are ongoing. A CE marking of the material is expected to be completed in 2022.

Furthermore, the wound patch version of the new material is undergoing trials in veterinary care, for treating pets. The

company Amferia AB is already collaborating with a number of veterinary clinics around Europe where the hydrogel is now being tested.

“Amferia has recently entered into a strategic partnership with Sweden’s largest distributor of premium medical & diagnostic devices to jointly launch these wound care products for the Swedish veterinary market during 2021” says Martin Andersson.

MORE ABOUT ANTIMICROBIAL PEPTIDES AND THE NEW MATERIAL The beneficial properties of antimicrobial peptides have been known for some decades, and thousands of different varieties occurring in the natural immune systems of humans, animals and plants have been discovered.

Researchers have long tried to mimic and use their natural function to prevent and treat infections without having to use traditional antibiotics. However, because the peptides are broken down as soon as they come in contact with blood or other body fluids, successful clinical usage has proved elusive. The researchers knew that smart new solutions were needed to protect the peptide from degradation. The new material in the study has been shown to work very well, allowing the peptides to be applied directly to wounds and injuries on the body, with the effect of both preventing and treating infection. The material is also non-toxic, so it can be used directly on the skin. The potential of this new material can also be seen in the flexibility that it offers for different types of products. “So far, we have mainly envisioned the material as a wound care dressing, but we are working on a new study investigating the potential for a wound care spray,” says Edvin Blomstrand.

THANK YOU TO OUR CONTRIBUTORS Varuni Paranavitane IP Solicitor, AA Thornton Varuni is an IP solicitor with a research background in Biochemistry and experience advising on patent, trade mark, design rights and copyright issues. She has IP experience in a variety of industry sectors including fashion, life sciences, digital media, sports and food & drink. Varuni’s practice also includes non-contentious brands advisory work, enforcement strategy, settlement and co-existence strategy advice as well as advice in relation to commercial transactions. Varuni has had litigation experience in courts in the UK as well as coordinating multi-jurisdictional pharmaceutical disputes across the globe.

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New platform enhances delivery of gene therapies Scientists have developed polypeptide-based materials that act as effective vectors for delivering gene therapies. The first-of-its-kind platform enables the vectors to be adapted to suit the specific gene therapy cargo.

The work, led by researchers from RCSI University of Medicine and Health Sciences and funded by Science Foundation Ireland, is published in Biomaterials Science.

scaffold accelerated bone tissue regeneration, with a six-fold increase in new bone formation compared to a scaffold alone.

A major challenge for gene therapies is preparing them in a way that can deliver the genetic information into the host cells. For the Covid-19 vaccines that use mRNA technology, the genetic information is delivered in a lipid nanoparticle to maintain its stability and deliver it into cells. The success of the COVID vaccines has established nanoparticles as key to the development of many advanced therapies.

“With the success of the COVID-19 vaccines, the potential of gene therapies is becoming apparent, and advanced nanoparticle delivery systems are key to enabling their use clinically. We have shown that these nanoparticles have real potential to be a game changer in the delivery of gene therapies,” said Professor Sally-Ann Cryan, the study’s senior author and Professor of Drug Delivery, RCSI.

The researchers developed a platform that produces bespoke star-shaped polypeptide nanoparticles, which effectively deliver a range of therapies, including gene therapies. Crucially, these polypeptides are more flexible and easier to handle than lipids. To demonstrate the potential of this material, the researchers used it to deliver a gene therapy that regenerated bone.

“While more testing is needed before these therapies can be used clinically, our platform allows us to design our polypeptides to meet a variety of delivery scenarios and provide tailored solutions to gene delivery challenges,” added Professor Andreas Heise, project collaborator and Professor of Polymer Chemistry, RCSI.

In preclinical work, the researchers loaded the material with DNA molecules that promote bones and blood vessels to regrow. They placed these nanomedicines in a scaffold that could be implanted into a defect site and deliver the genetic cargo into infiltrating host cells. The gene-loaded

“We are developing this patent-protected technology towards commercialisation, with support from an Enterprise Ireland Commercialisation Fund Award, and are seeking expressions of interest from industry partners and investors.”

“With the success of the COVID-19 vaccines, the potential of gene therapies is becoming apparent, and advanced nanoparticle delivery systems are key to enabling their use clinically. We have shown that these nanoparticles have real potential to be a game changer in the delivery of gene therapies.”

Professor Sally-Ann Cryan, Professor of Drug Delivery, RCSI

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The Nagoya Protocol and the UK – Are you Compliant?

The Nagoya Protocol has been in force in the UK since October 2015 and obliges users of genetic resources and traditional knowledge associated with genetic resources to comply with due diligence requirements before its ‘utilisation’. There is also an obligation to make a due diligence declaration on receiving research funding and at the final stages of product development. The legislation carries penalties for breach and alarmingly, users may be ordered to discontinue their work if the relevant documentation is not in place. This legislation is relevant to the pharmaceutical, biotechnology, food and feed, animal breeding, plant breeding, and cosmetic sectors.

The UK Office for Product Safety & Standards (OPSS) has indicated that it will start to carry out audits on research institutions and industry this year. Currently, digital sequence information does not fall within the scope of the Nagoya Protocol, but it is likely that benefit sharing legislation will be put in place.

One main challenge is that the legislation is unclear. the source from which the genetic resources were directly obtained

WHAT IS THE ORIGIN OF THE NAGOYA PROTOCOL? In 1994 the United Kingdom ratified the Convention on Biological Diversity, an international piece of legislation with 3 main objectives:

the presence or absence of rights and obligations relating to the access and benefit sharing and obligations regarding subsequent application and commercialisation

1. the conservation of biological diversity;

access permits, where applicable

2. the sustainable use of the components of biological diversity; and

prior informed consent and to agree to mutually agreed terms before ‘utilisation’ takes place

3. the fair and equitable sharing of benefits arising out of the utilisation of genetic resources.

make due diligence declarations to Defra upon receipt of research funding and at the final stage of development of a product

The Nagoya Protocol applies to the third objective.

Obtaining an internationally-recognised certificate of compliance as well as mutually agreed terms will remove the need for some of the documentation.

PROVIDER AND USER COUNTRY OBLIGATIONS Over 120 countries are signed up to the Nagoya Protocol and each country has the power to regulate access to genetic resources in their territory. The provider country may make access subject to prior informed consent and may require benefits from their use to be shared on mutually agreed terms. The provider country must provide legal certainty, clarity and post its relevant legislation in ABS Clearing House1. The UK government has chosen not to exercise sovereign rights for accessing its genetic resources under the Nagoya Protocol. Therefore there is no requirement to carry out due diligence for any utilisation of UK genetic resources for the purposes of the Nagoya Protocol.

Users are required to keep the documents for 20 years after the end of the period of utilisation.

WHAT HAPPENS IN A PUBLIC HEALTH EMERGENCY? A short extension is allowed in fulfilling due diligence requirements in relation to utilisation of genetic resources determined to be the causing pathogen of a ‘public health emergency of international concern’, such that a user may begin utilisation before the documentation is in place. However, after the short extension has passed, the user cannot claim patent rights nor continue with the utilisation until all the documentation is in place. This aspect of the legislation is of concern and highlights the importance of complying with the legislation.

The user country (in this case the UK) must take effective measures to ensure that genetic resources utilised within the UK have been accessed in accordance with the rules of the provider country. Therefore the key is to check the requirements of the provider country.

WHAT ARE THE PENALTIES FOR BREACH?

DOES THE NAGOYA PROTOCOL APPLY TO YOU?

The penalties for non-compliance are wide ranging and include powers of inspection and entry, discontinuation of the utilisation, monetary fines and criminal proceedings.

If you are ‘utilising’ a ‘genetic resource’, the Nagoya Protocol applies.

‘Genetic Resource’ is defined as ‘any material of plant, animal, microbial or other origin containing functional units of heredity of actual or potential value’.

ENSURING DUE DILIGENCE Researchers should make it policy to ensure due diligence is exercised, according to the Nagoya Protocol. For instance, maintaining lists of research projects involving genetic resources, recording which projects fall within and outside the scope of the Nagoya Protocol, compiling documentary evidence or reasons for projects falling out of scope.

‘Utilising’ is defined as ‘to conduct research and development on the genetic and/or biochemical composition of genetic resources including through the application of biotechnology’.

NOTE: Human genetic resources fall outside the Nagoya Protocol and the Nagoya Protocol applies only to genetic resources accessed after October 2015.

If you have any questions in relation to the Nagoya Protocol or patent protection for your invention, please contact Varuni Paranavitane at vxp@aathornton.com or visit aathornton.com.

WHAT ARE YOUR OBLIGATIONS? Users are required to exercise due diligence by seeking, keeping and transfering to subsequent users, documentation in relation to the below, before utilisation of a genetic resource or associated traditional knowledge:

1 https://absch.cbd.int/

the date and place of access of genetic resources the description of the genetic resources utilised

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Vortex Biosciences appoints new CEO Vortex Biosciences, the cancer diagnosis biotechnology business, has announced the appointment of Dr Adrian Kinkaid as its new chief executive officer.

Vortex Biosciences has developed the VTX-1, a best-inclass instrument that isolates and purifies Circulating Tumor Cells (CTCs) from blood. These cells can then be used for cancer diagnosis and monitoring, research on drug development, cancer research and development of personalized medicine.

Dr Kinkaid joins Vortex Biosciences on contract, alongside his other roles as CEO of healthcare diagnostic biotech BioFab Ltd and antibody testing biotech Lumabs BV. A specialist in leading early-stage start-ups, he led several funding rounds for MIP Diagnostics, a synthetic antibody biotech, where he served as CEO for four years until 2019. He has also secured non-dilutive funding for MIP Diagnostics and BioFab via the prestigious SMART Awards.

Prior to this, he was chief commercial officer for Promexus, a protein biotherapeutics company based on Affimer technology, and Strategic Market Development Leader for Abcam, the leading provider of research antibodies. He has a particular passion for improving patient outcomes and game-changing new technologies, especially in the in vitro diagnostics space.

Dr Kinkaid will now oversee the operations of Vortex Biosciences across its two sites in San Francisco, US and Cambridge, UK, using his expertise and experience to help Vortex Biosciences commercialize its medical technologies and grow rapidly in the liquid biopsy market. He will be working closely with executive chairman Dr. Ilian Iliev and the board of directors.

“Vortex is in an unrivalled position with outstanding core technology and a best-in-class platform to provide Circulating Timor Cells (CTCs) with remarkable efficiency and purity,” he said. “More importantly, Vortex’s VTX-1 platform is providing game-changing opportunities for CTC isolation in the liquid biopsy market.”

Dr Adrian Kinkaid

“Vortex is in an unrivalled position with outstanding core technology and a best-in-class platform to provide Circulating Timor Cells (CTCs) with remarkable efficiency and purity. More importantly, Vortex’s VTX-1 platform is providing game-changing opportunities for CTC isolation in the liquid biopsy market.” Dr Adrian Kinkaid

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Online ‘library of properties’ helps to create safer nanomaterials Researchers have developed a ‘library of properties’ to help identify the environmental impact of nanomaterials faster and more cost effectively.

Whilst nanomaterials have benefited a wide range of industries and revolutionised everyday life, there are concerns over potential adverse effects - including toxic effects following accumulation in different organs and indirect effects from transport of co-pollutants.

The European Union H2020-funded NanoSolveIT project is developing a ground-breaking computer-based Integrated Approach to Testing and Assessment (IATA) for the environmental health and safety of nanomaterials.

Over the last two years, researchers from the University of Birmingham have worked with experts at NovaMechanics, in Nicosia, Cyprus to develop a decision support system in the form of both stand-alone open software and a Cloud platform.

The team has developed a freely available cloud library containing full physicochemical characterisation of 69 nanomaterials, plus calculated molecular descriptors to increase the value of the available information, details of which are published in NanoImpact.

Professor Iseult Lynch, from the University of Birmingham commented: “One of the limitations to widespread application of computer-based approaches is the lack of

“Making the library of calculated and experimental descriptors available to the community, along with the detailed description of how they were calculated is a key first step towards filling this datagap.”

Professor Iseult Lynch, the University of Birmingham

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large well-organised high-quality datasets, or of data with adequate metadata that will allow dataset interoperability and their combination to create larger datasets.”

“Making the library of calculated and experimental descriptors available to the community, along with the detailed description of how they were calculated is a key first step towards filling this datagap.”

Development of the cloud-based nanomaterials library is the fifth freely available web-based application that the project has delivered.

Antreas Afantitis, from NovaMechanics, commented: “Over the last two years, this project has already presented some very impressive results with more than 30 publications, making NanoSolveIT one of the most active projects in the nanomaterials safety and informatics space.”

Concerns about nanomaterials are also arising as risk assessment is lagging behind product development, mainly because current approaches to assessing exposure, hazard and risk are expensive and time-consuming, and frequently involve testing in animal models. The NanoSolveIT project aspires to address these challenges.

The latest development aims to enrich our knowledge of nanomaterials properties and the link from property to (cytotoxic) effect. The enriched dataset contains over 70 descriptors per nanomaterial.

The dataset was used to develop a computer-based workflow to predict nanomaterials’ effective surface charge (zeta-potential) based on a set of descriptors that can be used to help design and produce safer and more functional nanomaterials.

The resulting predictive read-across model has been made publicly and freely available as a webservice through the Horizon 2020 (H2020) NanoCommons project (http://enaloscloud.novamechanics.com/nanocommons/ mszeta/) and via the H2020 NanoSolveIT Cloud Platform (https://mszeta.cloud.nanosolveit.eu/) to ensure accessibility to the community and interested stakeholders.

In addition, the full data set, ready for further computational modeling, is available through the NanoPharos database, as the project consortium supports the FAIR data principles - committing to making its data Findable, Accessible, Interoperable and Re-usable.

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UK ‘Octopus’ trial tackling multiple sclerosis is a world first A ground breaking mega-trial for progressive multiple sclerosis will be launched in the UK later this year.

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ctopus, so called because of its multiple arms, is a revolutionary clinical trial that will transform the way treatments for progressive MS are tested. It could deliver desperately needed new options up to three times faster.

Dr Emma Gray, assistant director of research at the MS Society, said: “More than 130,000 people live with MS in the UK and there are tens of thousands with progressive forms who have nothing to stop their MS getting worse.

“But we believe we can stop MS, and the launch of Octopus is a crucial moment in our journey towards that goal.”

Made possible by charity funding, Octopus will test several drugs – rather than just one – against a placebo at the same time. The trial will also combine what would normally be two consecutive trial phases into one. By bringing together lots of trials in this way, Octopus could rapidly speed up the development of new treatments.

Prof. Olga Ciccarelli is a leading magnetic resonance imaging expert in the field of MS and has been instrumental in developing Octopus.

“Octopus is a game changer for how MS clinical trials are run,” she said. “As well as testing many treatments at the same time with only one placebo arm, we’ll use an interim analysis of MRI scans to allow us to progress to the next stage much quicker.”

If scans showed a treatment was slowing the rate of brain shrinkage, it could be assumed the pace of advancing disability would also slow down. The results would need to be investigated across hundreds of participants.

“Any treatments not showing potential in the MRI analysis will be dropped, so we’re not wasting time or resource on treatments unlikely to be successful,” said Prof. Ciccarelli

Susan said: “When I was diagnosed with MS there wasn’t much to treat my condition. But in twenty years there’s been an absolute explosion of treatments available to me. I want more people with progressive MS to have the same options I do.

“I know a young woman who, when I first met her, had just recently starting using a wheelchair. Within three years, she had no arm function or head support, and her voice had virtually gone. I feel passionately that we must work together to do something about this.”

She said she had been very impressed with the in-depth patient representation on the Octopus trial. Patients had directly influenced how participants would receive information, including newsletters, social media and good old-fashioned mail.

Dr Emma Gray said: “Decades of research have got us to a critical point and our ambition to speed up clinical trials is ready to become a reality.

“Right now our amazing MS researchers are finalising which treatments Octopus will test first and later this year we hope to start recruiting people with progressive MS to take part.”

Octopus is just one of many vital research projects made possible by the MS Society’s Stop MS Appeal, which aims to raise £100 million to find treatments for everyone with MS. www.mssociety.org.uk

“Ultimately it’s a much more efficient trial and a major step forward in the search for progressive MS treatments.”

The flexible approach also means the trial team can continually update Octopus as their knowledge evolves.

If they discovered another effective treatment in the laboratory, that too could be quickly slotted in, rather than having to wait years to set up a whole new trial.

Susan Scott, from Ashwell in Hertfordshire, was diagnosed with the relapsing form of MS in 2001. For over eight years she has been working with researchers and the MS Society to develop Octopus, representing the perspective of people living with MS.

About multiple sclerosis Over 130,000 people live with MS in the UK MS damages nerves, making it harder to do everyday things such as walking, talking, eating and thinking It is relentless, painful and disabling

“Octopus is a game changer for how MS clinical trials are run. As well as testing many treatments at the same time with only one placebo arm, we’ll use an interim analysis of MRI scans to allow us to progress to the next stage much quicker.”

It can be unpredictable and different from person to person Approximately 85% of people with MS are diagnosed with the relapsing form, where symptoms come in sudden attacks, then fade Two in three of them will go on to develop secondary progressive MS, where there is no remission and they become increasingly disabled 10-15% of people have primary progressive MS, where symptoms gradually get worse from the outset.

The MS Society has a free helpline on 0808 800 8000 and a website at www.mssociety.org.uk

Prof. Olga Ciccarelli

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New fund energises search for motor neurone disease treatments Teams working on research that could translate into treatments for Motor Neurone Disease have been bidding for support from a new £1m joint fund.

Medical research charity LifeArc and the MND Association have established the joint translational research fund to support researchers to develop treatments for MND building on recent advances in understanding the mechanics of the disease. Despite those advances, there is still no effective clinical treatment for MND.

BOTH LIFEARC AND THE MND ASSOCIATION HAVE CONTRIBUTED £500,000 TO THE FUND. THE MND ASSOCIATION’S SHARE IS PART OF THE £2.2M RAISED BY KEVIN SINFIELD OF RUGBY LEAGUE CLUB LEEDS RHINOS

Researchers from across the UK and the Republic of Ireland are now having their applications for grants up to £500,000 considered following the application deadline of June 10.

Their translational research projects must be focused on developing new therapies or repurposing existing treatments for MND. Although the research has to be UK or Ireland-led, applications from teams working with international partners were acceptable.

Both LifeArc and the MND Association have contributed £500,000 to the fund. The MND Association’s share is part of the £2.2m raised by Kevin Sinfield of rugby league club Leeds Rhinos. He ran seven marathons in seven days last December – inspired by former teammate Rob Burrow, who was diagnosed with MND a year earlier.

Dr Brian Dickie, director of research development at the MND Association, said: “Our understanding of the causes of this devastating degenerative condition has improved dramatically over the last two decades, but clinicians are still unable to offer their patients any truly effective treatments.

She said: “This work fits with LifeArc’s approach over the last 25 years to translate early science into health care treatments or diagnostics that can transform patients’ lives.

“The fund will plug the gap between fundamental research into MND disease mechanisms and possible treatment options reflecting advances in our understanding of those mechanisms.

“This is about stimulating the search for effective treatments: now that scientists understand the mechanisms of the disease, they can build on that knowledge to identify and eventually test potential practical treatment approaches.”

“Our partnership with the MND Association is the latest in a series of strategic collaborations that leverage LifeArc’s expertise in driving strong discoveries from the lab into benefitting patients with conditions that have no or few effective treatment options.”

The fund will therefore support teams that are working on: Developing candidate therapeutic entities (e.g. small molecule drugs, antibody drugs or gene therapies) Pre-clinical testing of novel therapeutics in vitro or in vivo Pre-clinical validation for existing therapeutics that could be repurposed for MND Early-phase clinical trials (phase 1/2) of novel therapeutic compounds Early-phase clinical trials of existing therapeutics repurposed for MND.

“These advances have driven MND to the forefront of neurological disease research and we want to capitalise on that momentum. The research we are seeking to fund will build on that enhanced basic scientific understanding to develop potential therapies. That is how we can begin to offer real hope to people with the condition and their families.”

Kevin Sinfield, who is now Leeds Rhinos’ director of rugby after a long playing career with the club, said: “We have seen over the last year the vital work that can be done by researchers and scientists when they are given the vital resources they need. MND is not incurable; it has just been underfunded and our hope, like that of everyone affected by this brutal disease, including Rob, is that this money will make a real difference and help find the breakthrough we all desperately want.”

Dr Catriona Crombie, head of LifeArc’s Philanthropic Fund, emphasised that the focus of the new fund is on boosting research that already has a strong scientific foundation backed by credible data.

Successful projects will be expected to have a strong scientific rationale, be up to three years in duration and be target-driven with set milestones and a credible delivery plan – including a clear route to reach MND patients.

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| disease |

Genome sequencing reveals how salmonella carves out a niche in pork production Variants of concern (VOCs) and variants of interest (VOIs) have become familiar terms due to the current pandemic, but variants of familiar pathogens such as salmonella also present a threat to human and animal health.

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o better understand the different threats these variants pose, a collaboration led by Prof. Rob Kingsley, from the Quadram Institute, and Prof. Mark Stevens, from the Roslin Institute, working with scientists from the Earlham Institute has focused on common variants of salmonella present in pigs in the UK. Their findings, published recently in the journal Communications Biology, has shown that despite being extremely closely related, variants can have very different effects on the health of the pig and also on the risks they pose to food safety.

Salmonella Typhimurium is one of the most common types of Salmonella. It is a major cause of human gastroenteritis, notably from consuming undercooked pork products or as a result of cross-contamination of foods consumed raw.

This bacterial pathogen is also a concern to the pork industry as it can affect the health, productivity and welfare of pigs. Salmonella Typhimurium is relatively common in pig herds globally, and processes implemented in abattoirs are designed to prevent contamination of meat destined for the food chain.

Bacterial pathogens continually evolve to exploit new ecological niches. Human activity, including agricultural practices and how we use medicines and antibiotics may drive the emergence of new variants. Understanding exactly how this happens is crucial to countering the consequences of new variants on human and animal health, and the answers lie in the genes of the bacteria.

Genome sequencing can read all of an organisms genes and can help by resolving relationships between variants, identifying variants that are evolving as they enter a new niche, and pinpointing potential functional changes that affect their ability to cause disease or survive in the food chain.

The team worked with Public Health England and the Animal and Plant Health Agency and to examine salmonella isolates from human clinical infections during routine diagnostics or from animals during routine surveillance, with funding from the Biotechnology and Biological Sciences Research Council, part of UKRI. Using whole genome sequencing the research team found that two types of S. Typhimurium, dubbed U288 and ST34, have been circulating in UK pigs since 2003. Surprisingly, U288 are rarely associated with human infection, while ST34 account for over half of all S. Typhimurium infections from all sources, not just pigs.

What is more, the two types of Salmonella infected pigs differently, resulting in distinct levels of colonisation of the intestine and surrounding tissue, and disease severity in the first few days after infection. The U288 variant grew more slowly in the lab and was more sensitive to stress associated with desiccation. These characteristics may affect its ability to survive in the food chain.

Inspection of changes in the genome sequence of U288 indicated that this variant emerged by a unique set of changes that occurred within a short period of time, probably between the years 1980 and 2000. The researchers believe that these changes hold the key to understanding how this variant interacts differently with pigs during infections, in the lab, and potentially the food chain.

“We have seen these types of changes before in variants of salmonella that have become adapted to specific host species and cause a more invasive disease, including the type of salmonella that causes typhoid fever in people but

Prof. Rob Kingsley Quadram Institute

“We have seen these types of changes before in variants of salmonella that have become adapted to specific host species and cause a more invasive disease, including the type of salmonella that causes typhoid fever in people but does not affect other species.” does not affect other species,” said Prof. Rob Kingsley, a group leader at the Quadram Institute and professor of microbiology at the University of East Anglia.

Dr Matt Bawn, a researcher involved in the study based at both the Earlham Institute and Quadram Institute, said: “One of the interesting findings is just how rapidly pathogens can adapt, and how even a few genomic changes can lead to very different disease outcomes.”

Prof. Stevens, chair of microbial pathogenesis and a deputy director at the Roslin Institute, University of Edinburgh, added: “Understanding how variants of salmonella emerge and pinpointing the genetic signatures responsible for adaptation to different hosts and the ability to produce disease will provide opportunities to improve diagnostics and surveillance.

“In turn, this will help to predict the risk that salmonella variants pose to animal health and food safety.”

Reference: Kirkwood, M., Vohra, P., Bawn, M. et al. Ecological niche adaptation of Salmonella Typhimurium U288 is associated with altered pathogenicity and reduced zoonotic potential. Commun Biol 4, 498 (2021). https://doi.org/10.1038/ s42003-021-02013-4

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| news |

£7m invested in fight against antimicrobial resistance Phico Therapeutics Ltd, a biotechnology company developing engineered phage technology as the basis of a new generation of antibiotics to overcome antibacterial resistance, has announced £7m in new investment.

The financing was led by growth capital investor BGF, which invested £3 million, and was joined by other existing Phico investors.The funds will be used to support the continued development of Phico’s SASPject technology platform and in particular the progression of its lead product, PT3.9, towards the clinic.

The funding follows a recent announcement that Phico has been awarded a grant of up to $18.2 million USD (circa. £13.2 million GBP) to support the development of SASPject PT3.9 from Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), a global non-profit partnership dedicated to accelerating antibacterial research to tackle the global rising threat of drug-resistant bacteria.

SASPject PT3.9 is being developed for the intravenous treatment of hospital infections due to the bacterium, Pseudomonas aeruginosa. Phico’s SASPject platform delivers pan-spectrum anti-bacterial proteins called small acid-soluble spore proteins, or SASPs, to selected bacterial species using engineered bacterial viruses which inactivate the bacteria’s DNA leaving them unable to metabolise or reproduce.

The Phase I clinical trials will be first-in-man, intravenous studies and will focus on establishing the safety and kinetics of PT3.9 in healthy volunteers and, potentially, patients with ventilated hospital acquired pneumonia and ventilator associated pneumonia.

The increasing multi-drug resistance of P. aeruginosa strains has resulted in the U.S. CDC (Centers for Disease

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Control and Prevention) classifying P. aeruginosa as a serious threat to human health, and the World Health Organisation classifying it in the top three bacteria needing new treatments. With the bacteria being a leading cause of pneumonia in hospital patients, especially those on a ventilator, the SASPject platform could provide a much needed alternative to conventional antibiotic treatments.

Tim Rea, investor at BGF, said: “This is an extremely exciting time for Phico Therapeutics, and we are delighted to be partnering with this innovative business and expanding our presence in Cambridge and UK life sciences.

“BGF’s long-term approach to patient capital is a good match for this dynamic business, which has been at the forefront of building technological solutions to antibacterial resistance for over 20 years. We are thrilled to be working with Dr Heather Fairhead and the management team in helping them to realise the next great milestone for the company.”

Dr. Heather Fairhead, Phico Founder and CEO, said: “We are delighted that BGF has made this investment alongside many of Phico’s existing investor base.

Coupled with the recent award from CARB-X, these funds will enable the company to exemplify the technology in first in human intravenous studies. This is a very exciting time for Phico and we’re looking forward to great things ahead.”

| BIOSCIENCE TODAY |

| laboratory technology |

3D PRINTED LIVER AIDS LIFE SAVING SURGERY Surgeons will perform liver resections with greater accuracy and deliver improved patient outcomes thanks to new research by Nottingham Trent University. Senior research fellow Richard Arm has developed a way to 3D-print scan data of cancer-hit patient organs so that clinicians can rehearse difficult operations on lifelike models.

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The aim is for them to become familiar with the hidden complexities of an operation – which are unique from patient to patient – prior to the real surgery.

A prototype 3D-printed model liver – based on an anonymised cancer patient – features the tactile qualities of a real diseased organ, including imitation blood and different tissue hardnesses, such as the blood vessels, liver tissue and the tumour itself.

The model – made from synthetic gels and fibres - even allows surgeons to use real surgical tools to practice endoscopies and laser ablation techniques, during which arteries are resealed by laser to prevent a patient bleeding out during surgery.

“Surgeons have an incredibly complicated job to remove some tumours to save people’s lives,” said Richard, who runs the Flexural Composite Research Laboratory for the Advanced Textiles Research Group (ATRG) in the School of Art and Design.

“But due to the limitations of existing technologies available to them, many surgeons only discover the true complexities of an operation when they are in the midst of the live procedure itself.

“Every patient is unique and has organs of different shapes, sizes and constructs, so there can be many hidden complications that they have to deal with.”

However, his research has shown that adapting scan data and new 3D-print processing methods could dramatically improve the quality of the preparation before the first incision is even made.

“It could give surgeons increased confidence and may provide patients with improved outcomes, such as the increased retention of healthy tissue, reduced risk of infections and swifter recovery times,” he said.

The research also considers the potential for teaching trainee cancer surgeons in traditional and robotic tumour removal and could improve robotic surgical interfaces and operator proficiency. It could also allow surgeons to become more familiar with using robots to perform surgery remotely.

The project was funded by Nottingham Trent University’s Medical Technologies and Advanced Materials fund and the School of Art & Design. Expertise in material testing and tissue characterisation was provided by Dr Arash Moghaddassian Shahidi, also of Nottingham Trent University’s ATRG, while scan data and medical expertise was provided by Dr Christopher Clarke, consultant radiologist at Nottingham University Hospitals NHS Trust.

Until now, surgeons for the most part have had to rely on 2D images of the tumour and affected anatomy to plan surgery, and on rare occasions, have used animal livers to train for biopsy and tumour extraction.

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| laboratory technology |

“It could give surgeons increased confidence and may provide patients with improved outcomes, such as the increased retention of healthy tissue, reduced risk of infections and swifter recovery times.”

Richard arm, the Flexural Composite Research Laboratory for the Advanced Textiles Research Group (ATRG) in the School of Art and Design While there have been examples of people 3D printing livers based on patient data in the past, they have all been rigid in design, reliant on the capabilities of the printer in use to create a 3D representation of the organ, offering no opportunity for the practice the procedure being planned.

THE TUMOUR IMPLANTED IN THE PROTOTYPE 3D LIVER MEASURES 12 TO 15MM AND IS CLASSED AS A GIANT TUMOUR, AS ANYTHING OVER 10MM IN DIAMETER IS.

Richard said: “Rehearsing the surgery was never an option before this work, so we have taken things to the next level by transforming the rigid artefacts into biofidelic tissues representative of the living patients anatomy.”

“The physical properties and location of a tumour can now be understood in advance - how it feels, where it lies, how it responds to the force applied of surgical tools and intervention strategies.

The tumour implanted in the prototype 3D liver measures 12 to 15mm and is classed as a giant tumour, as anything over 10mm in diameter is. It sits nestled between two large veins which sit on the upper posterior of the organ, meaning a surgeon would have to go in from the front (in open surgery) and manoeuvre the liver into position to access and remove the tumour, without, crucially, rupturing a blood vessel.

But being able to practise in advance would allow the surgeon to perform keyhole surgery, going up through the vein to ablate the tumour using a laser.

The fact the model liver is reusable means it can also be

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taken into the lecture theatre to teach budding oncology surgeons the ropes.

“Unique to this work, we have created hollow blood vessels too,” said Richard. “Not only do they feel realistic, but they also have the right hardness and shape, because they are printed using the blood volume of each vessel.

“A surgeon would be able to use an endoscope to navigate round the vessels to trace the blood supply to the tumour.”

Pushing forward, the team aims to develop the 3D technology further to include other organs and connective vascular networks.

The real starting point for their work on transforming rigid prints into something surgeons could practise on began in 2016, when they produced a set of biofidelic heart and lungs. However, that was produced for trauma purposes and had no real internal anatomy.

The Nottingham Trent team has even more ambitious goals in sight now. “We’re working our way through the human anatomy,” said Richard. “It would be nice to do the rest of the organs, including the stomach, kidneys and intestines and the greater vessels that feed all these organs.

“Maybe one day we’ll be able to print the entire anatomy of a human being, so surgeons or even robots can learn on it without risk to patients and grow to a level of proficiency that has never been seen before.”

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| innovation |

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| innovation |

A transformative roadmap for neurotechnology in the UK Innovation experts, KTN, publish roadmap calling for multi-million pound investment to develop and commercialise ground-breaking treatments for disorders of the brain and nervous system.

The human brain remains one of the great unknown frontiers and the more we understand about it, the more unknowns we discover. However, one thing we do know is that advances in neurotechnology enhance our understanding of brain function, which in turn opens up new methods of repairing and interfacing with the nervous system – often in ways that other treatments cannot. There are great opportunities to be realised in this sector, both in economic terms and impact on human health, and as we live longer lives, keeping our brains healthy is becoming increasingly important.

For the past two years, KTN has been convening the community through its Neurotechnology Innovation Network with the purpose of creating a new strategy for a bright future ahead for the UK. Other major economies around the world, including the US, China, Australia and South Korea, are investing heavily in neurotechnology, and the UK has the opportunity to capitalise on its leading academic research and join the race to become a world leader in this space.

A new report, published by KTN, aims to show the path towards scaling up the UK’s development and manufacture of breakthrough technologies; creating innovations which can alleviate pain and symptoms of patients with brain injury, stroke, chronic disease, Parkinson’s and depression to name a few. The report also highlights several non-medical application opportunities from the gaming sector to education and the military.

The report is co-authored by Dr Charlie Winkworth-Smith, who leads the Neurotechnology Innovation Network at KTN, and Royal Academy of Engineering Chairs in Emerging Technologies Prof Tim Denison (University of Oxford) and Prof Keith Mathieson (University of Strathclyde).

For the UK to derive strong economic value and societal benefit from neurotechnology, investment is key; and the report calls for a multi-million pound investment to create a coherent national strategy with robust regulatory and ethical frameworks. To generate a pipeline of new technologies to become market-ready, investment is needed in basic research, and support towards commercialisation, whilst ensuring there are sufficient people being trained in a multidisciplinary way.

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One of the proposals is the formation of a Neurotechnology Accelerator, which will become an essential test bed for device developers and provide key infrastructure to industry – a crucial stepping stone in making the UK internationally competitive in this area.

Championing the report is Prof David Delpy, Chair of the RAEng Healthcare and Biomedical Engineering Topic Group. He says: “I genuinely believe that a strategic research investment in neurotechnology, alongside a co-ordinated investment in businesses, would allow the UK to take an international lead in this area. This roadmap provides demonstrated evidence of this need.

“With an ambitious strategy, delivered collaboratively, we can transform UK neurotechnology research and industry, establish a strong national ecosystem for the sector, improve the quality of life for patients, reduce pressure on the NHS and better prepare the UK for the challenges of an ageing population.”

Dr Tim Constandinou, Reader in Neural Microsystems, Imperial College London and co-chair of the Royal Society’s iHuman: Blurring lines between mind and machine report, adds: “This roadmap sets out the opportunity the UK has to become a world leader in neurotechnology, an area which could transform medicine and human interaction. With ambitious investment, the field could bring huge economic benefits and put the UK at the forefront of medical innovation in the coming decades.

Some applications of the emerging area also raise critical ethical questions, which would be best addressed as a key component of a national neurotechnology strategy.”

One example of a UK firm already providing patient treatment with neurotechnology is Magstim, based in Carmarthenshire, Wales. They have pioneered and developed Transcranial Magnetic Stimulation (TMS) – a neurotechnology which can treat depression, particularly in patients which have not responded to antidepressant medication. With TMS magnetic pulses stimulate the brain to increase chemicals such as monoamine oxidase that activates and heals neurons, which in turn lifts the patient’s mood. It is safe, fast and non-invasive. TMS delivers electromagnetic pulses to the brain increasing brain activity and areas of the brain that regulate mood therapy treating depression, a disorder affecting millions of patients that increased 25% since the Covid pandemic, according to the WHO. TMS is also used as a research tool to better understand how fundamental brain physiology and to identify new treatments for many brain disorders. A video case study on Magstim’s work is available to watch AT https://ktn-uk.org/news/a-transformative-roadmap-forneurotechnology-in-the-uk

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| drug development & discovery |

TWO NEW FORMS OF THERAPY GIVE HOPE WHEN BLOOD CANCER RETURNS AND BOWEL CANCER SPREADS

Scientists trial new way to boost CAR T-cell therapy Cancer Research UK is collaborating with Aleta Biotherapeutics to trial a new therapy that reboots a treatment for some people whose blood cancer starts to come back.

The new therapy, called ALETA-001, aims to boost a treatment called CAR T-cell therapy, which takes some of a patient’s immune cells and alters them to attack cancer.

Cancer Research UK’s Centre for Drug Development will fund, sponsor and conduct the clinical trial of ALETA-001, which will involve people with B cell lymphoma and leukaemia.

REBOOTING CAR T-CELL THERAPY Nigel Blackburn, Cancer Research UK’s director of drug development, said this is a landmark collaboration for Cancer Research UK. “It’s the first-in-human trial for a new drug that reboots CAR T-cell therapy, and we look forward to progress its early clinical development with Aleta.”

CAR T-cell therapy works by taking some of a patient’s T cells and altering them to recognise a particular protein found on lymphoma and leukaemia cells, called CD19. After a few

“There is an urgent need to develop new therapies that can help people with B cell cancers, such as lymphoma and leukaemia, whose cancer has progressed after treatment with CD19 CAR T-cell therapy.”

Paul Rennert, President, co-founder and chief scientific officer of Aleta Biotherapeutics

weeks, these cells are then fed back into the bloodstream and attack cancer cells.

“CAR T-cell therapy has been transformative in treating patients with hard-to-treat blood cancers, but many will see their cancer return and treatment options begin to run out,” said Blackburn.

Around half of the patients treated with CAR T-cell therapy relapse, mostly because their cancer cells stop producing the CD19 protein that CAR T-cells are looking for.

When this happens, patients have few other options.

ALETA-001 acts as a reboot for CAR T-cell therapy, attaching to a different protein called CD20 and recoating the cancer cell with CD19. The CAR T cells can then recognise and attack the cancer cells again.

“ALETA-001 uses a simple yet elegant method to redirect a patient’s circulating CD19 CAR T cells against cancer cells expressing CD20, and we hope this could be a new treatment avenue for blood cancer,” said Blackburn.

TAKING ALETA-001 TO THE CLINIC The first trial will enrol patients with B cell lymphoma or leukaemia who have received CD19 CAR T-cell therapy but did not achieve a complete response or whose cancer has come back.

Led by a team at The Christie NHS Foundation Trust in Manchester, it will be the first time that this type of therapy has ever been tested in humans.

A key aim of the trial is to find out the right dosage of ALETA-001. After this, it will be move into a much bigger trial in the US involving people with diffuse large B cell lymphoma.

This second trial will be designed to support potential accelerated approval of ALETA-001 for cancer patients.

Paul Rennert, President, co-founder and chief scientific officer of Aleta Biotherapeutics, said: “There is an urgent need to develop new therapies that can help people with B cell cancers, such as lymphoma and leukaemia, whose cancer has progressed after treatment with CD19 CAR T-cell therapy.”

“We look forward to working with Cancer Research UK’s exceptional network of experienced clinical trial investigators and researchers to conduct the trial.”

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| drug development & discovery |

Combination immunotherapy for advanced bowel cancer approved for NHS in England People who have previously been treated for a type of bowel cancer that’s spread to other parts of their body will now have another treatment option in England, following the approval of nivolumab (Opdivo) and ipilimumab (Yervoy).

The National Institute of Health and Care Excellence (NICE) has approved this combination of immunotherapy drugs for use in adults with bowel cancer that has spread to other parts of the body (metastatic bowel cancer) and has a lot of errors (mutations) in its DNA. Ben Chiu, policy manager at Cancer Research UK, said that this decision is “excellent news” for people with this type of cancer. “Even though some uncertainty remains, clinical evidence suggests that nivolumab plus ipilimumab can improve patients’ survival and help maintain their quality of life.”

AN UNMET NEED Around 4 in 100 metastatic bowel cancers have a lot more DNA mutations than others, as they’re unable to repair any mistakes that are made in their DNA. These cancers are said to have high ‘microsatellite instability’ (MSI) or ‘mismatch repair (MMR) deficiency’, which can make them more aggressive, and are associated with a poorer outlook and greater risk of death.

Despite this, there aren’t specific treatments for this type of bowel cancer, so people are offered the same treatment whether or not their cancer has this inability to fix mistakes in its DNA. Patient experts explained to the NICE committee that this kind of diagnosis affects the quality of life both physically and psychologically, and that new treatments like the newly approved immunotherapy drugs are needed.

People with previously treated metastatic bowel cancer are currently offered combination chemotherapy as their second-line treatment.

But following the NICE decision, patients with bowel cancer that has high MSI or an MMR deficiency will now have an option of a combination of immunotherapies.

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WHY DOES IMMUNOTHERAPY WORK BETTER FOR THESE PATIENTS? Immunotherapies harness the body’s immune system to fight cancer. Researchers have found that bowel cancer tumours with high MSI or MMR deficiency have a lot of immune cells within them, but the cancer stops them from working. Nivolumab and ipilimumab block the cancer’s ability to do this, allowing the immune cells to attack the tumours.

Experts commented that having the immunotherapy combo rather than combination chemotherapy may mean less debilitating side effects. The absence of side effects like nausea, stomach pain and fatigue could give people a better quality of life.

The clinical evidence for the effectiveness of this treatment came from the single-arm, phase 2 CheckMate 142 study.

The trial included 119 people with metastatic colorectal cancer with high MSI or MMR deficiency, previously treated with combination therapies.

As a single-arm trial, the study did not directly compare the use of nivolumab plus ipilimumab with other treatments, so the data had to be compared indirectly with data about current treatments.

The NICE committee concluded that despite this uncertainty, the trial showed that the benefits of the treatment, measured by overall survival for patients and the amount of time where their cancer didn’t get worse, was likely to be greater than current standard care.

Overall, the treatment was considered cost-effective for use in the NHS by NICE and will now be an option on the NHS in England. NICE decisions are usually adopted in Wales and Northern Ireland as well, so the decision is likely to affect patients in all 3 nations. Scotland has a separate process for reviewing drugs.

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| climate sense |

SAGES TEACH THE ART OF ADAPTING TO CLIMATE CHANGE

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| climate sense |

While the conversation about climate change has been dominated by mitigation, what is equally crucial is the need to adapt to the unavoidable changes already on their way. “We have absolutely no choice but to learn to adapt to a future with a very different climate,” says environmental consultancy Climate Sense. “It is imperative organisations act now.”

By Helen Compson Editor in Chief

For 20 years now, the experts behind environmental consultancy Climate Sense have been driving the subject of adaptation to climate change up the political agenda.

It is no small measure of their success that this year, in Glasgow, Climate Sense director and technical lead Prof.

John Dora is developing related sessions for COP26 in partnership with the University of Birmingham, the Strengthening Infrastructure Risk Management in the Atlantic (SIRMA) Project and the International Standards Organisation (ISO).

The 26th UN Climate Change Conference of the Parties will also be the first COP to boast a Resilience Hub, dedicated specifically to the prerequisites of adapting to climate change.

Eighteen years ago, it was an entirely different story, says Doogie Black, director and lead analyst at Climate Sense.

Back then, organisations simply didn’t grasp the onus on them to act responsibly and act now!

Tasked, in an EU-funded post, with raising awareness about the need to prepare for the impact of a future climate that will be more severe than the one we have, Doogie faced an uphill struggle in 2003.

Until very recently, any talk about climate change has tended to be about mitigation – the need to reduce carbon emissions and to preserve/bolster the carbon sequestration potential of our forests and peat bogs.

Few have considered the other side of the equation. Doogie said: “Even if we managed to stop all emissions right now, the repercussions of the damage we have already done will continue for at least another 30 years, and there’s no chance of us stopping that.”

In his determination to open up the conversation and to get individuals and organisations alike to step up to the plate, he began studying human behaviour in the process of decision-making.

What would make people accept and address the need for adaptation, he wanted to know. And what type of support would encourage them to embed adaptation to climate change in their decision-making?

The five years of EU funding he received gave him the opportunity to engage with some of the “biggest brains in the world” to propel adaptation into European consciousness.

By the time he started up his own consultancy in 2008, Doogie himself was a leading expert on behaviour change and adaptive capacity.

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John Dora at COP23 A key member of the team that developed the Capacity Diagnosis & Development framework, rated as being the most effective method in the field, he has since applied the framework to assessing more than 2000 public, private and civil society organisations all over the world.

But in the beginning, his primary function was one of education. “I was going out looking at the adaptive capacity of organisations, their people and their systems. I had developed the software and the metrics to do that, so I thought I had the best consultancy in the world, because everyone needs this,” he laughed.

“But then I realised nobody knew they needed it. At that time, there was still a lot of argument going on about whether climate change was natural or human-induced.

“It’s a different world today. Slowly people are coming to understand that we are talking about the adaptation efforts

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| climate sense |

required for the human race to survive. People are prepared to have that conversation today.”

showed that it was much more cost-effective to act on adaptation sooner rather than later,” said Doogie.

Since 2017, Doogie has been a member of the British Standards Institute’s Adaptation to Change Committee, the national body responsible for ensuring the matter is fully incorporated into UK and, where possible, European and International standards.

“A lot of decisions we make today have ramifications that will last well into the future.

In 2019, he and John Dora launched Climate Sense. The two had met while drafting ISO14090, the first ever international standard on adaptation to climate change.

Indeed, John, the global lead for adaptation for the International Standards Organisation, chaired the international working group concerned. A world-class authority on infrastructure and adaptation, his clients have included the World Bank, the United Nations, the Asian Development Bank, the European Bank for Reconstruction and Development, and CEN/CENELEC, the European standards organisations.

Doogie, meanwhile, the Principal UK Expert in the writing of ISO14090, has been appointed by the European Commission to write guidance on how to embed adaptation to climate change within new and existing European Infrastructure Standards (through CEN-CENELEC), and by the German Environment Agency to research and make recommendations on best practice in standardisation across Europe.

The Climate Sense team as a whole continues to promote, educate and encourage in relation to the responsibility of organisations to do the right thing. “In the UK as far back as 2006, the Stern review of the economics of climate change

“Take the built environment. A bridge or dam or school or hospital might have a design life of 40 years, but it will probably sit there for well over a 100 years and yet planning permission is still being given for building to take place on flood plains without any consideration for the flooding of the future.

“Organisations and institutions are starting to recognise that they need to make better decisions today if they and the outcomes of what they do are to survive.”

This month, Climate Sense added a new weapon to its arsenal in the form of an NVQ course entitled Adaptation to Climate Change.

Developed and rolled out in partnership with L&DA, well-established providers of education, qualifications and assessment of competence in the water industry, the course is designed to teach people how to build resilience and sustainability in an organisation.

Participants learn how to measure and develop the adaptive capacity of their organisation, their people and their systems and how to ensure adaptation to climate change is embedded in decision-making processes in the most constructive way. resiliencetoclimatechange.com climatesense.global

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Doogie chairing the EBRD Conference Bishkek

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| news |

THE FORCE OF LIVING CELLS EXERTED AT WARP SPEED MEASURED Scientists at the University of St Andrews have learned to measure the tiniest forces living cells exert at sheer WARP speed.

mechanical characterisation of spontaneous oscillatory contraction (SPOC) waves, which are ripples of weak mechanical activity that flow through cells in between their main contractions.

As first published in Nature Communications, the team of researchers, led by the School of Physics and Astronomy, have developed an advanced microscopy technique that greatly accelerates and simplifies our ability to study how cells interact with their environment.

SPOC waves may be involved in regulating the heartbeat by creating an intermediate phase between contraction and relaxation. The team are currently investigating using WARP to shed further light on this.

Wavelength alternating resonance pressure microscopy (WARP) provides near instantaneous maps of the extremely weak mechanical forces that living cells exert on their surroundings.

WARP allows scientists to record mechanical information about cells in real-time, a process that has previously required extensive offline computations to obtain results. Being able to record data in real-time opens a door to high throughput screening of the mechanical impact that new drugs may have on cells.

It will also enable biologists who work with cell cultures to look at mechanical aspects more routinely than is currently possible.

The research team, led by Professor Malte Gather from the School of Physics and Astronomy at the University of St Andrews, demonstrated that WARP can resolve the forces that cause the periodic contractions of heart muscle cells. Of particular interest in this context is the

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To measure mechanical forces, WARP employs thin film interference, the same phenomenon that gives soapbubbles their rainbow-like colours. By illuminating a thin and soft probe with light of two slightly different colours in quick succession, the researchers can accurately and unambiguously infer by how much cells have deformed the probe.

The current work is part of a larger research effort funded by the Engineering and Physical Sciences Research Council (​EPSRC) involving scientists from the University of St Andrews and the University of York that looks at exploiting optical resonances and the shaping of light to improve the understanding of biological systems.

The paper ‘Real-time imaging of cellular forces using optical interference’, Andrew T. Meek, Nils M. Kronenberg, Andrew Morton, Philipp Liehm, Jan Murawski, Eleni Dalaka, Jonathan H. Booth, Simon J. Powis and Malte C. Gather is published on the Nature Communications website: http://doi.org/10.1038/s41467-021-23734-4

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New Jurassic flying reptile has the oldest opposed thumb A new 160-million-year-old arboreal pterosaur species, dubbed ‘Monkeydactyl’, has the oldest true opposed thumb - a novel structure previously not known in pterosaurs.

An international team of researchers from China, Brazil, UK, Denmark and Japan have described a new Jurassic pterosaur Kunpengopterus antipollicatus, which was discovered in the Tiaojishan Formation of Liaoning, China.

It is a small-bodied darwinopteran pterosaur, with an estimated wingspan of 85 cm. Most importantly, the specimen was preserved with an opposed pollex (“thumb”) on both hands.

The species name ‘antipollicatus’ means ‘opposite thumbed’ in ancient Greek, in light of the opposed thumb of the new species. This is the first discovery of a pterosaur with an opposed thumb. It also represents the earliest record of a true opposed thumb in Earth’s history. The researchers published their discovery today in the journal Current Biology.

A true opposed pollex is mostly present in mammals (e.g. primates) and some tree frogs, but extremely rare among extant reptiles except for chameleons. This discovery adds to the list that darwinopteran pterosaurs such as K. antipollicatus also evolved an opposed thumb.

The research team scanned the fossil of K. antipollicatus using micro-computed tomography (micro-CT), a technique making use of X-ray to image an object. By studying its forelimb morphology and musculature, they suggest that K. antipollicatus could have used its hand for grasping, which is likely an adaptation for arboreal life.

In order to test the arboreal interpretation, the team analysed K. antipollicatus and other pterosaurs using a set of anatomical characters related to arboreal adaptation.

The results support K. antipollicatus as an arboreal species, but not the other pterosaurs from the same ecosystem. This suggests niche-partitioning among these pterosaurs and provides the first quantitative evidence that at least some darwinopteran pterosaurs were arboreal.

Fion Waisum Ma, co-author of the study and PhD researcher at the University of Birmingham, said: “The fingers of ‘Monkeydactyl’ are tiny and partly embedded in the slab. Thanks to micro-CT scanning, we could see

“The fingers of ‘Monkeydactyl’ are tiny and partly embedded in the slab. Thanks to micro-CT scanning, we could see through the rocks, create digital models and tell how the opposed thumb articulates with the other finger bones.”

Fion Waisum Ma, PhD researcher at the University of Birmingham

Life reconstruction of K. antipollicatus. The opposed pollex could have been used for grasping food items, as well as clinging and hanging to trees.

Image credit: Chuang Zhao through the rocks, create digital models and tell how the opposed thumb articulates with the other finger bones.

“This is an interesting discovery. It provides the earliest evidence of a true opposed thumb, and it is from a pterosaur - which wasn’t known for having an opposed thumb’ she added.

Xuanyu Zhou from China University of Geosciences who led the study commented: “Tiaojishan palaeoforest is home to many organisms, including three genera of darwinopteran pterosaurs. Our results show that K. antipollicatus has occupied a different niche from Darwinopterus and Wukongopterus, which has likely minimized competition among these pterosaurs.”

Rodrigo V. Pêgas from Federal University of ABC, in Sao Bernardo, Brazil, said: “Darwinopterans are a group of pterosaurs from the Jurassic of China and Europe, named after Darwin due to their unique transitional anatomy that has revealed how evolution affected the anatomy of pterosaurs throughout time.

“On top of that, a particular darwinopteran fossil has been preserved with two associated eggs, revealing clues to pterosaur reproduction. They’ve always been considered precious fossils for these reasons and it is impressive that new darwinopteran species continue to surprise us!”

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