BioScience Today 26

SCIENCETODAY

BIO

DMT - Assisted therapy • LIFE SCIENCES • LOW TESTOSTERONE • PERSONALISED MEDICINE Trials

ISSUE26

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www.biosciencetoday.co.uk

| foreword |

foreword New year, new era of innovation Karen Southern Editor in chief

Editor Karen Southern karen.southern@distinctivegroup.co.uk

Design Distinctive Publishing, 3rd Floor, Tru Knit House, 9-11 Carliol Square, Newcastle, NE1 6UF Tel: 0191 580 5990 distinctivepublishing.co.uk

Advertising Distinctive Publishing, 3rd Floor, Tru Knit House, 9-11 Carliol Square, Newcastle, NE1 6UF Tel: 0191 580 5477 e: liz.hughes@distinctivegroup.co.uk distinctivepublishing.co.uk

Words such as ‘spiritual’ and ‘life-affirming’ aren’t normally bandied around in traditional medical circles.

dependence on ‘conventional’ pills and therapy … only time will tell! Read more about Small Pharma’s work on pages 12 to 14.

But a recent resurgence of research has shown the potential benefit of using psychedelic drugs in tandem with therapy to treat major depressive disorders. And the results are so promising that the UK regulator last year approved the first clinical trials with dimethyltriptamine (DMT).

R&D is of course one of the cornerstones of UK life sciences. The sector is entering yet another era of exciting innovations, reconfiguring boundaries that seemed impossible only a few years ago. But obstacles remain.

Early experimentation with psychedelic drugassisted therapy were documented in the 1950s and 60s, but fizzled out once ‘illegal’ substances became associated with the hippy subculture, causing a mainstream backlash.

However, breakthroughs such as the latest DMT trials – carried out by UK company Small Pharma in collaboration with Imperial College London – seem to show that neural pathways can be literally reset, ending the perpetual loop of depressive thoughts.

Will this radical reassessment of the treatment of depressive disorders signal the end of our

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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The sector is on an upward trajectory, with massive investment streams championed by a government who sees life sciences as a key area of economic growth. However, the ecosystem feeding R&D, specialist skills and lab space needs nurturing too.

As life sciences development expert Charles Walford points out on pages 16 to 18, a vast amount of capital may be available … but it’s not matched by the space needed to accommodate the industry.

Creating a truly viable life sciences ecosystem needs business support at all stages of growth.

Will 2022 be the year when the sector can start to Build Back Better too? Let’s hope so.

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| contents |

features

Novel therapy solution to low testosterone

16 12 Changing the way we think about depressive disorders.

2022: The year for UK LIfe Sciences?

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| contents |

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contents / www.biosciencetoday.co.uk / issue 26 /

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Foreword

4-5

Contents

7-10

NEWS

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intellectual property The Benefits of Ensuring your Invention is Plausible

12-14

DMT - Assisted therapy A ‘spirit molecule’ from the Amazon could be a game changer in the treatment of major depressive disorders. Dr Carol Routledge, of Small Pharma, talks to Karen Southern about her pioneering work with DMT.

16-18

LIFE SCIENCES Charles Walford, Senior Development Director and Head of Life Sciences, Stanhope PLC, considers the opportunities and challenges facing the UK’s life sciences ecosystem.

20-23

LOW TESTOSTERONE For the first time in over 70 years, a new testosterone replacement therapy has been unveiled.

24-27

PERSONALISED MEDICINE Trials Kate Shaw, CEO of Innovative Trials, investigates one of the biggest challenges facing clinical research today.

28-34

24 Driving a need for greater diversity

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NEWS

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| industry contributors |

Alex is a UK and European qualified patent attorney with extensive experience in identifying and protecting innovations, and has spent many years working in-house in the medical device and diagnostic field.

Through his work with big corporates and multinationals Alex is able to bring a wealth of knowledge to his work with SMEs and start-ups to provide leading strategic IP advice.

Dr. Carol Routledge Chief Medical and Scientific Officer at Small Pharma Carol is an R&D professional and drug development expert with over 30 years’ of experience across UK and US based pharmaceutical and biotechnology companies and the non-profit sector with a focus on drug acquisition and profiling of NCEs and biologics. Her preclinical and clinical experience spans psychiatric and neurological indications, with a strong focus on understanding and treating mental health disorders. Carol is responsible for oversight of all clinical, preclinical and associated regulatory functions at Small Pharma. She holds a 1st Class Honors degree in Zoology and a PhD in neuropharmacology.

Kate Shaw Founder and CEO of Innovative Trials Kate Shaw is the founder of a UK-based clinical trials patient recruitment company, and has more than 20 years’ experience in patient recruitment support for clinical research. Her company has worked with pharmaceutical companies on nearly 200 clinical trials, recruited around 40,000 people into clinical research and played a role in six new treatments being approved for patients across the world.

to advertise or contribute to the next edition advertising: liz.hughes@ distinctivegroup.co.uk editorial: karen.southern@ distinctivegroup.co.uk

BIO

SCIENCETODAY

Alex Bone Patent Attorney, Partner, AA Thornton

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| news |

“Cardiovascular disease is the leading cause of death in Europe, responsible for 45 per cent of all deaths.”

AI used to improve cardiovascular risk prediction AI startup Owkin and Amgen have announced the results of a three-year project using artificial intelligence to more accurately predict cardiovascular risk. This study demonstrates the ability of AI to improve the way that clinicians predict patients’ risk of suffering major cardiovascular events, such as strokes and myocardial infarctions.

Using data from 13,756 patients who were part of FOURIER, a large Amgen clinical trial, Owkin trained a machinelearning algorithm to predict those at higher risk of cardiovascular events. Published in the European Heart Journal - Digital Health, the results show that machine learning is more efficient and effective than the statistical models routinely used by clinicians.

medical records being more complete and prevalent than ever before, the use of machine learning to better predict cardiovascular risk could have wide application.

For five years, Owkin and Amgen have been collaborating on projects across cardiology, hematology and oncology to develop clinical applications for artificial intelligence.

Last month, Owkin became a ‘unicorn’ – a start-up valued at over $1 billion – through a $180 million investment from Sanofi, which was announced alongside $90 million of joint cancer research projects.

Jean-Frédéric Petit-Nivard, SVP Commercial & Product Strategy at Owkin, said: “We are delighted that our collaboration, which began in 2016, has yielded compelling scientific results that could fundamentally improve patient monitoring and treatment. We look forward to continuing this project with Amgen to translate these scientific findings into clinical applications.”

Cardiovascular disease is the leading cause of death in Europe, responsible for 45 per cent of all deaths. It represents a considerable economic burden, costing an estimated €210 billion in the European Union alone.

By better predicting which patients will suffer major cardiovascular events, patient outcomes and efficiency can be drastically improved.

Adrien Rousset, Head of Augmented Diagnostics at Amgen, said: “After more than three years of collaboration, we are very proud to have our results recognized and published in a prestigious scientific journal for cardiologists worldwide.

We hope that this work will contribute to the next generation of tools that will help in saving more lives.”

By improving the ability to predict cardiovascular events, clinicians are better able to prevent them. Identifying at-risk patients sooner will allow them to benefit from better care, adapted to their individual risk profile. Thus, identified patients will benefit from better follow-up and therapeutic management adapted to their risk level. With electronic

Dr. Marc S. Sabatine, the Lewis Dexter, MD Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, said: “This project has allowed us to explore the value of Machine Learning for cardiovascular risk prediction and gain important insights into the use of clinical data.”

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| news |

A microscopic image of the mini stomachs used in the research. Credit: Giovanni Giobbe

Lab-grown ‘mini-stomachs’ could shed light on children’s COVID symptoms A ‘lab-grown model’ of the human stomach, that can be used to study how infections affect the gastrointestinal system, has been developed for the first time.

A UCL-led team of international scientists have built on recent advances to grow ‘mini-organs’ in a laboratory, known as organoids.

These organoids provide researchers with invaluable tools to study how organs function both when they are healthy and when impacted by disease.

The team includes Great Ormond Street Hospital (GOSH), UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) and the Istituto Zooprofilattico Sperimentale delle Venezie (Legnaro, Italy).

In the study, published in Nature Communications, scientists have for the first time described how to grow ministomach organoids, across differing stages of development – foetal, child and adult.

To do this, researchers, based at Zayed Centre for Research into Rare Disease in Children, isolated stem cells from patient stomach samples, and grew them under special conditions in the lab to obtain mini-stomachs in a dish that mimic the behaviour of a human stomach.

As the COVID-19 pandemic progressed, several hospitals reported gastrointestinal symptoms alongside the more usual respiratory effects like coughs and breathing difficulties, particularly in children.

Following these cases, the research team, led by Dr Giovanni Giuseppe Giobbe, Professor Nicola Elvassore and Professor Paolo De Coppi from UCL GOS ICH, and Dr Francesco Bonfante from Istituto Zooprofilattico Sperimentale delle Venezie, determined that their ministomach model could be used to study how a SARS-CoV-2 infection affects the stomach.

The scientists were able to facilitate the infection of the mini-stomachs from the outside by exposing the surface of the cells to the virus. From this they showed that SARSCoV-2 could replicate within the stomach, more noticeably in organoids that were grown from the child and late foetal cells, compared to adult and early foetal cells.

The research team were also able to look at the impact of the infection on the cells within the organoids, showing that a specific group of cells, called delta cells that make a hormone called somatostatin, had died, which could explain some of the stomach symptoms seen in patients.

The team’s laboratory results mirror the pattern of gastrointestinal symptoms seen in patients of different ages.

Professor Paolo De Coppi, (GOSH Consultant Paediatric Surgeon and UCL GOS ICH Nuffield Professor of Paediatric Surgery), senior author said: “This study has highlighted that SARS-CoV-2 infection may begin to infect the gastrointestinal system via the stomach in children and young babies. We hope that this adds another piece to the puzzle as we try to build our understanding of the impact of the virus across the body. As a research team we are proud to have been able contribute to the global fight against coronavirus in this way, pivoting our research as the need arose.”

The team now plan to continue their work utilising these new mini-stomachs, aiming to study how the stomach develops from early in pregnancy through to adulthood.

They also hope to look at the effects of other common gastrointestinal infections.

Dr Giovanni G Giobbe (UCL GOS ICH Senior Research Associate) and co-lead author on the study said: “We have been able to develop the first foetal model of the stomach and have demonstrated that the human gastric organoids can be used to accurately study real-world infections.

“Developing reliable models of organs that scientists and doctors can study in a lab are vital as they allow us to work out how organ tissue is affected during disease and infection. We want to increase our understanding of how infections impact the stomach so that we can further the search for new treatments.”

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| news |

Bacteria can develop strong immunity for protection against viruses A new study hopes to exploit newly characterised defence systems in bacteria to compare changes to the human genome.

University bioscientists have been working on the research to demonstrate the complex workings of bacterial innate immunity.

Bacteria have evolved a multitude of defence systems to protect themselves from viruses called bacteriophages. Many of these systems have already been developed into useful biotechnological tools, such as for gene editing, where small changes are made to the target DNA. The researchers demonstrated that two defence systems worked in a complementary manner to protect the bacteria from bacteriophages.

One system protected the bacteria from bacteriophages that did not have any modifications to their DNA. Some bacteriophages modify their DNA to avoid this first defence system. A second system, called BrxU, protected the bacteria from those bacteriophages with modified DNA, thereby providing a second layer of defence.

The researchers built an extremely detailed 3-D picture of BrxU to better understand how it protects from bacteriophages with modified DNA. BrxU has the potential to be another useful biotechnological tool, because the same DNA modifications that BrxU recognises appear throughout the human genome, and alter in cancer and neurodegenerative diseases.

Senior author of the study, Dr Tim Blower, an Associate Professor and Lister Institute Prize Fellow in Durham University’s Department of Biosciences, said: “Being able to recognise modified DNA is crucial, as similar modifications are found throughout the DNA of the human genome.

“This extra layer of information, the “epigenome”, alters as we grow, and also changes in cases of cancer and neurodegenerative diseases.

“If we can develop BrxU as a biotechnological tool for mapping this epigenome, it will transform our understanding of the adaptive information controlling our growth and disease progression.”

Image credit: Dr Tim Blower, Durham University

The study findings from lead author Dr David Picton and coworkers are published in the journal Nucleic Acids Research.

Ninety-seven undergraduates, who were also involved, were in the final years of their BSc or MBiol degrees in the Department of Biosciences, Durham University.

As part of a Microbiology Workshop designed to provide research-led teaching, they were tasked with isolating new bacteriophages for study. These bacteriophages thankfully don’t harm humans, but just as the human immune system responds to infections, bacteria have been forced to evolve their own immune systems that protect from bacteriophages.

Bacteriophages were collected from the River Wear, college ponds and other waterways around Durham. They were then used to test the bacteriophage innate immunity in E. coli bacteria.

The study was led by a team of bioscientists from Durham University, UK, in collaboration with University of Liverpool, Northumbria University and New England Biolabs Research was funded in the UK by the Biotechnology and Biological Sciences Research Council Newcastle-LiverpoolDurham Doctoral Training Partnership, the Lister Institute of Preventive Medicine, Durham University’s Biophysical Sciences Institute, and the Wellcome Trust.

“Bacteria have evolved a multitude of defence systems to protect themselves from viruses called bacteriophages.”

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| news |

Ancient genes help dolphins live on Ancient genes that predate the last Ice Age may be the key to survival … at least if you are a dolphin!

Genes up to 2.3 million years old helped the bottlenose dolphin adapt to new habitats through changes in behaviour and may be the secret to their survival and range expansion, according to the research published in Science Advances.

Understanding the processes that allow species to extend their ranges and adapt to environmental conditions in a newly available habitat, such as coastal habitats at the end of the last Ice Age, is an essential question in biology.

The bottlenose dolphin is a highly social and longlived common species which has repeatedly adapted from being an offshore (pelagic) species to life in coastal waters. Key to their ability to adapt to changing environments over generations are ​genes associated with cognitive abilities and feeding behaviours, indicating that bottlenose dolphin sociality has helped them to adapt and survive.

Dr Marie Louis, visiting scholar in Professor Oscar Gaggiotti’s research group in the School of Biology at the University of St Andrews, said: “Old genes were important contributors to bottlenose dolphins’ ability to repeatedly adapt to coastal waters across the world.

“Furthermore, several of the genes involved in this repeated adaptation to coastal habitats have roles in cognitive abilities and feeding, suggesting a role of social behaviour in facilitating the ability of bottlenose dolphins to adapt to novel conditions.

“Conserving old genes may thus be critical for any species to cope with current rapid global change.”

The research team re-sequenced and analysed the whole genomes of 57 coastal and pelagic dolphins from three regions – the eastern North Atlantic, western North Atlantic and eastern North Pacific – to figure out how the bottlenose dolphin has been able to repeatedly adapt to coastal waters.

The team found that the pelagic and coastal ecotypes from the Atlantic and the Pacific have evolved independently, while those in the Atlantic are partially related.

Scanning the genomes for patterns of genetic diversity and differentiation, the team found that some regions of the genome were under the influence of selection in all three geographically distant coastal populations and were thus likely involved in adaptation to coastal habitats.

Even more striking was the fact that these genomic regions under parallel adaptation, and present at low to intermediate frequency in the pelagic populations, were very old.

This suggests that these old genes have been repeatedly repackaged during the formation of coastal populations, when new coastal habitats opened up, for example at the end of the last Ice Age. The international study, led by the University of St Andrews, involved the University of Montpellier, the University of Groningen, the Norwegian University of Science and Technology, the University of Copenhagen and the University of La Rochelle in collaboration with researchers from Scotland, Ireland, the United States and Switzerland.

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| intellectual property |

Is your Invention Plausible?

The market exclusivity provided by a patent can be crucial for allowing a company to obtain a return on their R&D investment.

Alex Bone

Patent Attorney, Partner, AA Thornton

A patent is essentially a deal in which, in return for an applicant disclosing their invention, a government grants the applicant the right to prevent third parties from exploiting that invention without the applicant’s permission. The idea is to encourage sharing of innovations to facilitate further technical developments. An applicant may consider limiting the disclosure to avoid giving competitors the full benefit of their R&D efforts, but this can cause problems with plausibility and prevent a patent from being granted so a balance must be found.

Neither the UK Patents Act, nor the European Patent Convention, explicitly refer to plausibility. Nonetheless, the concept features in decisions from both the UK Intellectual Property Office (UK IPO) and European Patent Office (EPO) and is generally used to prevent speculative applications, for example those containing broad claims but little or no technical information, from resulting in granted patents.

The UK IPO and EPO assess plausibility of an invention alongside sufficiency of disclosure. The assessment is based upon the information in the application as originally filed together with the common general knowledge of the skilled person in the technical field at the time of filing. An applicant cannot refer to data published, or made available, after an application has been filed in support of plausibility.

If it was not plausible that an invention would work across the full breadth of the claim at the time of filing, it will remain not plausible even if data is later filed to show that it actually does work across the breadth of the claim.

There is no requirement to provide experimental data or test results in a patent application. For applications in many technical fields this is not a problem as a particular technical result may be self-evident, or at least predictable.

However, in technical fields like pharmaceuticals, where results can be difficult to predict and beneficial effects may require experimental data to confirm, it is important to provide sufficient detail on filing to render a technical effect plausible across the entire breadth of the claimed invention. Merely stating that an effect is provided (instead of providing a range of examples and/or a reasoned explanation) may well be considered insufficient basis for plausibility.

The EPO may also consider plausibility in another situation.

Where a technical effect is relied upon to justify that an

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invention is not obvious (i.e. that it possesses an inventive step) the plausibility of that technical effect being provided can be important. When considering inventive step, and depending upon the plausibility of the technical effect, the EPO may consider data published, or made available, after an application has been filed as evidence of that effect.

Unfortunately the EPO’s current approach is not uniform.

Some EPO Boards of Appeal consider that a claimed technical effect must be plausible before they will consider such data in support. If sufficient detail or data is not present in the specification as originally filed this can lead to a squeeze in which the applicant must argue that the effect is plausible, for example with reference to published documents or common general knowledge, for data to be considered. Unfortunately arguments that a technical effect might be predictable from what is already known may lead the EPO to consider that the invention itself is obvious.

Other EPO Boards have adopted a much lower hurdle and will consider additional data in support of a claimed technical effect provided the claimed effect is not implausible, while yet other EPO Boards appear to consider that neither approach is appropriate due to incompatibility with the EPO approach to assessing inventive step using the “Problem/Solution” approach.

Some clarity regarding the approach that should be taken may be provided following a referral in October 2021 to the Enlarged Board of Appeal at the EPO (case G2/21) to look at this issue. The Enlarged Board is likely to take time to provide useful clarity so it remains advisable when filing a patent application to provide as much data as possible regarding the invention and any technical effects to try to avoid plausibility problems. Producing the experimental data that might be required takes time and there is often a compromise required between filing as soon as possible and delaying filing to ensure that sufficient data can be included.

If you have any queries regarding this topic, or other pharmaceutical or biotechnological matters, please contact Alex Bone at amtb@aathornton.com or visit aathornton.com

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| dmt - assited therapy |

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| dmt - assited therapy |

DMT-assisted therapy: changing the way we think about depressive disorders A ‘spirit molecule’ from the Amazon could be a game changer in the treatment of major depressive disorders. Dr Carol Routledge, of Small Pharma, talks to Karen Southern about her pioneering work with DMT. Psychedelic assisted drug therapy is not as ‘far out’ as it sounds - the therapeutic benefits of psychedelics such as LSD have already gained mainstream recognition.

reasons we selected DMT (N,N-Dimethyltryptamine) is that it induces a short psychedelic experience but has an expected long-duration antidepressant effect.

But exciting research into DMT, the ‘spirit molecule’ found in Amazonian brew ayahuasca, is showing real potential to transform mental health care.

“The whole treatment, including wraparound therapy and pharmaceutical dosing for DMT (our patented product is called SPL026), is predicted to be about two hours, whereas for other psychedelic candidates – such as psilocybin – it can take a whole day or more.

DMT is the active compound in ayahuasca, which can spark a short powerful psychoactive experience lasting less than half an hour. This makes it far more accessible for clinical use than other psychedelic compounds whose effects typically last for hours.

Combined with professional therapy, the treatment has the potential to shift a patient’s mindset.

In a world-first, Small Pharma has collaborated with Imperial College London to assess how DMT works hand-in-hand with psychotherapy. The Phase I clinical trial is now complete, with very promising results.

Dr Routledge, Chief Medical and Scientific Officer of UK-based Small Pharma, explained: “One of the

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“This means DMT is more clinically practical to work with.

Patients only need to be in the clinic for a relatively short amount of time and this makes it easier to incorporate into health systems around the world.”

Dr Routledge added: “While DMT has unique properties that could help treat major depressive disorders, it is worth highlighting the importance of the therapy that goes with it.

“The DMT acts as a catalyst – offering a powerful hyperconnected experience – but it is the talking therapy, the psychedelic experience in a meaningful way.

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| dmt - assited therapy |

Together, DMT and talking therapy could enable the increase in new neuronal connections in the brain – triggering a rapid-acting antidepressant effect that provides immediate relief from negative, ruminative thought patterns.” In other words, shifting the patient’s mindset helps reset neural connections away from constant negative repetitive loops and back towards normal thought patterns.

Dr Carol Routledge Chief Medical and Scientific Officer of UK-based Small Pharma

Treatment during the clinical trial has been administered in a highly controlled therapeutic setting with an emphasis on safety and trust. The trial started in January 2021, combining a Phase I and Phase IIa study to roll data over immediately.

Phase I’s main aim was to understand the the safety, tolerability, mechanistic and pharmacodynamic effects of DMT with therapy – including the intensity and quality of the psychedelic experience – so that a suitable dose could be selected from Phase I and taken into Phase IIa. Dr Routledge continued: “That dose of SPL026 – our DMT-based product – obviously needs to be safe and well-tolerated, but it also needs to elicit a full breakthrough psychedelic experience in all subjects being treated with an active drug.

“We successfully completed the Phase I component of our study, and we’ve now started the Phase IIa efficacy study, which is a proof-of-concept study in patients with major depressive disorder to assess efficacy and safety of DMT with therapy. We are due to get a headline data set in the first half of this year.”

The psychedelic experience is subjective, so differs from person to person. However, Dr Routledge says visual hallucinations are likely, which could include seeing geometric shapes. There may also be auditory hallucinations, a loss of sense of time and an out-of-body experience. She points out: “You don’t lose a sense of ‘you’, but you can perceive yourself in a slightly different way.

Sometimes people will have discussions with themselves.

This can be therapeutically beneficial, because people can talk through a lot of their issues.”

The psychotherapy – which is conducted on either side of the DMT dose – first of all ‘sets’ the patient for dosing.

Dosing anchors the experience and enables the trial participants to explain their experiences in a safe setting.

This is thought to help cement new connections and to inform any next steps with the participant.

Crucially, DMT is not expected to produce significant sideeffects. Dr Routledge explained: “There were no serious adverse effects in the Phase I component of our trial. DMT is not anticipated to be addictive or to have abuse liability based on current preclinical and clinical data.”

A successful scale-up will, of course, depend on having therapists with the right skills set; Small Pharma’s training programme launched in July 2021 to provide psychedelic training and training on the bespoke DMT therapy protocol.

Therapists involved in the first session are now working on the Phase IIa clinical trial, with training expanded to cover Phase IIb and Phase III clinical trials.

While Small Pharma is carrying out the world’s first formal trial on DMT and psychotherapy, other companies are focused on other psychedelic candidates. Compass Pathways, another UK company, is developing a patented form of psilocybin (COMP360) for use in conjunction

with therapy to treat patients with treatment-resistant depression, and recently reported positive results from their Phase IIb clinical trial.

Dr Routledge continued: “What is exciting is that the UK is quickly forging a leadership position in the world of psychedelic assisted therapy research. This is thanks to the world-leading academic institutions – such as Imperial College London – that are supporting various clinical trials.

The government should be delighted that such trailblazing innovation is happening right on its shores and grab the opportunity to lead on the global stage with both hands.”

Regulators’ reactions have so far been positive, she added.

“The UK Medicines and Healthcare products Regulatory Agency (MHRA) is supportive of our ambitions. In fact, earlier this year, the MHRA granted Small Pharma an Innovation Passport Designation for SPL026, the lead product from our pipeline of DMT-assisted therapies.

Similar to the FDA’s fast-track in the United States, the UK’s MHRA Innovation Passport provides us with access to specialist advice from MHRA partners such as NICE and the NHS throughout the drug development process. This has the potential to enable a speedier, more efficient development process for SPL026 with the aim of accelerating time to market.”

Subject to regulatory approval SPL026 is predicted to reach the market in 2026/27, and across the pond in the US, attitudes towards psychedelics are also changing.

Oregon became the first US state to create a legal system for supervised psilocybin experiences; California, Vermont and Hawaii are actively considering new legal frameworks for psychedelics. Meanwhile, John Hopkins Medicine received its first federal grant for psychedelic treatment research in 50 years.

The days of ‘conventional’ anti-depressants – and months and years spent on prescription medications –may well be numbered for millions of people around the world.

“The government should be delighted that such trailblazing innovation is happening right on its shores and grab the opportunity to lead on the global stage with both hands.”

Dr Carol Routledge, Chief Medical and Scientific Officer, Small Pharma

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| news |

Dr Paul Chazot and Dr Gordon Dougal demonstrate the PBM-T Helmet

Light therapy helmet could help dementia patients A new infrared light therapy has the potential to help people with dementia.

A pilot study recently investigated how transcranial photobiomodulation therapy (PBM-T) –transferred through a specially adapted helmet -- could boost memory, motor function and processing skills in healthy people.

The study, led by Dr Paul Chazot of Durham University and GP Dr Gordon Dougal of Maculume Ltd, yielded promising results which could possibly benefit people with dementia.

The PBM-T helmet delivers infrared light deep into the brain for six minutes at a time. This stimulates mitochondria that generate most of the chemical energy needed to power the biochemical reaction in brain cells.

The researchers believe this can lead to a rise in an organic compound called adenosine triphosphate (ATP), which is markedly lower in dementia patients. ATP provides energy to drive processes in living cells and helps repair nerve cells.

The therapy can also increase nitric oxide levels, and thus blood flow in the brain, by improving the flexibility of the membrane that lines the inside of blood vessels. This opens up blood vessels so more oxygen can reach deep into white brain matter.

The helmet is easy to wear, meaning the therapy can be delivered at home.

In a pilot study, improvements were detected in healthy people aged 45 and over, who received six minutes of therapy twice daily at a wavelength of 1068 nanometres over four weeks.

This included a significant improvement in performance in motor function (finger tapping), memory performance (mathematical processing, a type of working memory),

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delayed memory and brain processing speed.

Dr Chazot, who has spent 20 years studying particular infrared wavelengths for dementia treatment, said: "While this is a pilot study and more research is needed, there are promising indications that therapy involving infrared light might also be beneficial for people living with dementia and this is worth exploring.

"Indeed, we and our US research collaborators recently also published a new independent clinical study which provides the first evidence for profound and rapid improvement in memory performance in dementia."

He added that particular wavelengths of infrared light are known to help alleviate nerve cell damage.

Dr Dougal devised the £7,250 PBM-T helmet, which delivers infrared light deep into the brain from 14 fancooled LED light arrays. The County Durham GP said the helmet "may well help dying brain cells regenerate into functioning units once again". He added: "Much more research is needed to fully understand the mechanism of action."

Durham Uni researchers were also involved in two recently published, separate pilot Alzheimer’s disease clinical studies in the USA, looking at the effectiveness of the therapy. Those studies found a similar profound and rapid positive effect for men and women with mild to moderate dementia. Participants reported elevated mood, less anxiety, and having more energy.

Scientists stress that more research is needed, but that early findings are promising. It is also thought the therapy might have potential benefits for disorders like Parkinson’s, traumatic brain injury and motor neurone disease.

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| life sciences |

2022: The year for UK Life Sciences?

Charles Walford, Senior Development Director and Head of Life Sciences, Stanhope PLC, considers the opportunities and challenges facing the UK’s life sciences ecosystem.

White City Place

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| BIOSCIENCE TODAY |

| life sciences |

The past two years have propelled life sciences into the mainstream. The sector had already seen strong signs of growth, but the pandemic put the industry firmly at the front of the minds of governments, investors, and the public. Post-Brexit and post-Covid, the Government has made life sciences a key target for growth, pumping investment into homegrown start-ups and encouraging international companies to set up here.

has not suffered from the current crisis. Healthtech VC investment in the UK increased by 245% between January and November 2021 compared to 2020, making it the third most attractive location globally. The sector is clearly seen as being a cornerstone of the country’s future, which is extremely positive news for companies seeking funding.

As we enter 2022, the sector appears in rude health with the government and investors now acutely aware of the role that life sciences can play in helping the UK cement its reputation on the world stage. New data has shown that investor appetite for the UK life sciences sector

In terms of the ‘Build, Back Better’ agenda, the varied skills needed to successfully service life sciences spaces present local communities with an opportunity for inclusive growth, further stimulating government support and other investment.

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| BIOSCIENCE TODAY |

| life sciences |

But while the financial future of the sector is secure and growth will continue, there are also challenges to consider in the year ahead. MedCity, the organisation in charge of promoting the golden triangle, recently released a study into demand for life sciences space in London. The findings confirm that demand vastly outstrips supply, with a requirement of over 500,000 sq ft for London life sciences space not being met, and space provision growing at a much slower pace than is needed to sustain innovation.

One of the major challenges is that London’s incubators are full, with some sites having to turn enquiries away. There is a vast amount of capital in the sector, but not enough space to accommodate the industry.

Charles Walford

Whilst there are many proposed life sciences development projects across the country, the complex needs of companies coupled with the lack of industry data means that building speculative sites remains challenging. The sector is also highly location-sensitive. Companies need to be near research and academic institutions and teaching hospitals, which are usually in cities where finding the appropriate land in the right location is difficult. In addition, turning commercial spaces into lab-enabled buildings is costly.

Significant demand for space comes from smaller startups who require specialist spaces they can occupy easily.

Unlike managing a co-working office space, these science incubators require a high level of expert servicing. As these start-ups grow at a rapid pace, property developers need to provide spaces that can grow with them and support businesses throughout their life cycles. The presence of start-up companies also generates demand from mature corporates, who want to collaborate with or even acquire the intellectual property of those who have discovered on the cusp of developing something great but who may be in need of more capital to realise their potential. The presence of businesses at all stages of growth is what helps to create a supportive life sciences ecosystem.

The established and emerging clusters in London such as White City Place, King’s Cross, Whitechapel and the South Bank are proof that building a life sciences ecosystem is complex, but can be done. White City Place, for example, which is next to an Imperial College London campus, fosters an environment where life sciences companies at different stages are thriving.

As with many other industries, the life sciences sector faces challenges, but overall, it remains on an upward trajectory.

A continued positive trend will however rely on collective support from central and local government, investors and the wider industry to make it easier to deliver the required R&D spaces. The current shortage is clearly an issue that will need to be addressed if the UK to sustain its standing as a world leading destination for life sciences.

White City site map

“Healthtech VC investment in the UK increased by 245% between January and November 2021 compared to 2020, making it the third most attractive location globally.”

Charles Walford, Senior Development Director and Head of Life Sciences, Stanhope PLC

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| news |

Chimp chit-chat shows importance of gesture Bonobo chimpanzees communicate through gestures, just like humans do.

A study led by researchers at the University of St Andrews revealed that gestures between Bonobos can have multiple meanings, depending on specific contextual settings.

The team studied wild Bonobos in the Democratic Republic of Congo to see how they responded to specific gestures.

Lead researcher, Dr Kirsty Graham from the university’s School of Psychology and Neuroscience, said: “If the first bonobo raises her arm and the other bonobo comes to clean bits out of her hair, then the meaning is something like ‘please groom me’. Sometimes it’s just that simple, one gesture gets one response. But some types of gestures get a variety of different responses. For example, the arm raise gesture sometimes means ‘please groom me’ but it can also mean ‘please carry me’ or ‘let’s mate’. We wanted to find out

if the context in which gestures were used, and who they were directed at, alter the meaning of the gesture.”

In human language, syntax and context are very important for understanding words with multiple meanings. The team tested the importance of syntax and context of Bonobo gestures, and found that gestures used in sequences, or in certain positions in sequences, had no overall impact on overall meaning. However, the Bonobo’s actions when gesturing i.e. behavioural context, and the relationship between the signaller and recipient, did affect meaning.

Dr Graham added: “"We hope to soon be able to compare these findings with other great apes, including chimpanzees and gorillas, to better understand how important context is to our closest primate relatives."

“In human language, syntax and context are very important for understanding words with multiple meanings. “ 19

| BIOSCIENCE TODAY |

| low testosterone|

Acesis breaks new ground with novel therapy solution to low testosterone For the first time in over 70 years, a new testosterone replacement therapy has been unveiled. Dr Vassilios Papadopoulos and Dr Costas Karatzas, co-founders of Acesis BioMed, explain how their ‘first-in-class’ peptide therapeutics could transform men’s health across the world.

Low testosterone is a widespread clinical problem that affects up to 40% of the world’s male population and is linked to obesity, high blood pressure, infertility and other serious health issues.

High prevalence of hypogonadism (~ 40%) has been reported in patients with Type 2 Diabetes.

New research has also found that men with low testosterone are more likely to die from COVID-19.

Acesis is developing first-in-class non-steroidal oral peptide therapeutics which will induce endogenous testosterone production in testosterone-deficient males. Put simply, they are developing therapies that

instruct the body’s own cells to produce testosterone naturally.

All current Testosterone Replacement Therapy (TRT) treatments on the market are exogenous and based on old steroid technology developed in the 1930s. In 2015, potential side effects were flagged up about to their use, including stroke, heart attack, infertility and specific prostate cancer risk.

Acesis BioMed believes its product candidates will have a superior safety profile as the body is using its own cells to produce testosterone naturally.

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INTRODUCTION Acesis Biomed’s science and pipeline product candidates are based on the 30 years of research of Dr Vassilios Papadopoulos, a leading authority in the field of steroidogenesis. Co-founder, Director and Chairman of the Scientific Advisory Board at Acesis, Dr Papadopoulos discovered that a protein (14-3-3ε) acts as a negative regulator of steroidogenesis by forming a scaffold with the outer mitochondrial membrane voltage-dependent anion channel (VDAC1) protein that limits the availability of cholesterol for steroidogenesis.

In 2014/15 Dr Papadopoulos’s team discovered peptides which blocked the 14-3-3ε-VDAC1 interactions while at the same time increased VDAC1-translocator protein interactions that induced steroid formation in rat testes, leading to increased serum T levels.

This platform technology and novel method of inducing steroidogenesis occurred during his time as professor at McGill University, and as executive director at the Research Institute of the McGill University Health Centre, Montreal, where Dr Papadopoulos and Acesis’ current CEO, Dr Costas Karatzas, met. Acesis Biomed was founded shortly after this discovery to advance it through the appropriate drug development program, which involved identification of the lead peptide and extensive in-vitro and in-vivo testing.

Our current stage of development is to perform pre-IND and IND-enabling studies with our orally bioavailable tetrapeptide which is demonstrated to be inducing T production in the relevant models.

WHY IS YOUR PEPTIDE PRODUCT CANDIDATE CONSIDERED “FIRST IN CLASS”?

VP: A first-in-class medication is a pharmaceutical that uses a “new and unique mechanism of action” to treat a particular medical condition and is an indicator of the innovative nature of a drug. Our peptide-based product candidate is designed to have a mechanism of action

(targeting the 14-3-3ε-VDAC1 protein to protein interaction complex) which is different from those of existing testosterone therapies.

LOW TESTOSTERONE IS A MAJOR MEDICAL PROBLEM WITH A GROWING DEMAND FOR EFFECTIVE TREATMENTS, SO WHY HAVE THERE BEEN NO SIMILAR BREAKTHROUGHS IN OVER 70 YEARS? VP: In recent decades, the number of hypogonadal men with low testosterone has grown at a significant rate also due to the increase in the global average age. All existing treatments are exogenous in nature and based on a steroidal chemistry core initially developed in the 1930’s.

As a result, there has been an increasingly growing demand for the development of novel, safer and more effective treatments, a demand which has promoted new research into the field. Acesis is well positioned to service this demand with its peptide-based platform.

Our novel peptide-based product candidates are moving away from this antiquated steroid based chemical core, enabling the “recovery” of T production by the testes rather than replacing endogenous T resulting to supraphysiological levels and side effects.

CONGRATULATIONS ON IDENTIFYING YOUR LEAD PEPTIDE. COULD YOU EXPLAIN HOW TREATMENTS BASED ON THIS PRODUCT CANDIDATE WILL WORK AND WHAT INDICATIONS YOU WILL BE TARGETING? CK: Our mission at Acesis is to revolutionise the treatment of male hypogonadism, as well as a variety of other linked comorbidities and prevalent diseases. Acesis Biomed is looking forward to advancing its core program for the treatment of male hypogonadism and to pursuing partnerships and out-licensing opportunities with significant players in the pharmaceutical and biotechnology industries for the other co-morbidities of T deficiency. Some of these players may have lost market share due to the FDA Black-box warning for their T pipeline and may be seeking safer alternatives to treat hypogonadism or related co-morbidities.

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Vassilios Papadopoulos

Costas Karatzas

The Company currently owns two patent families which relate to peptide-based compounds, as well as their use for modulating endogenous steroidogenesis. We are in the process to transition our orally bioavailable lead ACE-167 peptide through pre-IND and IND-enabling studies prior to requesting the authorization of regulatory bodies to initiate clinical studies. The first indication which we are planning to transition into the clinic is male hypogonadism.

We are keen to progress our product candidate platform for a number of additional chronic disease indications where there is a strong, scientific evidence linking them to low testosterone. Many of these indications affect a significant proportion of the global population, including metabolic syndrome, non-alcoholic fatty liver disease, prediabetes, type 2 diabetes, osteoporosis and obesity.

Another condition of interest includes the Klinefelter syndrome, a chromosomal condition in boys and men that produce a reduced amount of testosterone. There is quite a range of reports indicating for example that opioid medications suppress testosterone levels, that sleep deprivation lowers testosterone but at the same time low T may contribute to insomnia, and it is notable that head trauma or concussions are a common reason for low T in younger men.

WHAT WILL BE THE MAIN BENEFITS OF YOUR THERAPEUTICS? CK: When compared to existing testosterone therapies on the market, Acesis Biomed’s product candidate is expected to have a significantly improved safety profile and be more effective. Our drug candidates will undergo extensive clinical testing and regulatory evaluation and designed with a novel mechanism of action (MoA)are positioned as a major innovation in the space in over 70 years. Testosterone Replacement Therapy (‘TRT’) methods are currently available in the market are exogenous and include: T-gels (eg. AndroGel, Testim® and Fortesta); oral (methyl-T, Jatenzo); buccal patches; implanted subcutaneous pellets (Testopel), long-acting T-injectable (Aveed), sub-cutaneous weekly auto-injector (Xyosted); transdermal patches (Androderm) and intranasal (Natesto). However, these treatments carry significant risks as reported by the FDA in

2014 and 2015 when a “black box warning” label was issued on these existing marketed T treatments.

IS THERE ANY EVIDENCE THAT LOW TESTOSTERONE IMPACTS COVID-19 INFECTIONS, AND IF SO, COULD TRT AID TREATMENT? VP: Testosterone replacement therapy has positive impact in men’s well-being, but if low testosterone is treated in a safer way under the direction of a qualified physician, it can help counter the signs and symptoms even earlier and more efficiently. With evidence that our testosterone recovery therapy could also target significant indications linked to low testosterone, including the likes of type II diabetes, the potential beneficial implications are extremely promising. Research into Covid-19, and the direct mechanisms which connect it with low testosterone, is still new and relatively ambiguous. According to National Geographic, for example, there is now a wealth of data that shows getting infected with Covid-19 can cause erectile dysfunction and other reproductive health problems for men.

IS THERE ANYTHING ELSE YOU WOULD LIKE TO ADD, FOR EXAMPLE, FUTURE EXCITING DEVELOPMENTS? CK: Testosterone Replacement Therapy represents a global market opportunity of $2-3 billion dollars. U.S. represents the vast majority of global sales at ~ $1.3 billion, with injectable formulations representing ~ 35% and gels ~ 60% of the dollar sales in 2020. Since the market is suffering from a lack of introduction of innovative products, it is believed that the testosterone replacement therapy market is likely to hit a patent cliff in the next 6 to 8 years.

All TRT products are based on very old T core chemistrybased derivatives and formulations for T delivery. The expiration of these patents would have an impact on firms’ TRT product revenues. As such, we are really excited at the possibility to progress the development of our lead candidate and take centre stage in what is becoming such an important and swiftly expanding market where T deficiency plays a major role.

WhileFull details about the therapeutics can be found at acesisbio.com.

“In recent decades, the number of hypogonadal men with low testosterone has grown at a significant rate also due to the increase in the global average age.”

DR Vassilios Papadopoulos, Co-founder, Director and Chairman of the Scientific Advisory Board at Acesis

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| clinical trials |

Personalised medicine: driving a need for greater diversity Kate Shaw, CEO of Innovative Trials, investigates one of the biggest challenges facing clinical research today.

Personalised medicines, particularly gene and cell therapies, offer new opportunities for treating serious conditions such as muscular dystrophy, cystic fibrosis and other complex conditions like cancer and diabetes.

From the development of trastuzumab (Herceptin) for the treatment of HER2-positive breast cancer to the availability of onasemnogene abeparvovec (Zolgensma), a gene therapy that slows disease progression in children with Type 1 Spinal Muscular Atrophy (SMA), targeted therapies are contributing to improved health and longer life. It is a long way from the early days of ‘one size fits all’ chemotherapy developed in the 1940s. It is therefore no surprise that the global personalised medicine market is expected to reach almost USD 800 billion by 20281.

But just as targeted therapies offer exciting promise, so too do they highlight an urgent need to address one of clinical research’s long-standing challenges - recruiting diverse patient populations into trials. Investigating the effectiveness of these therapeutics relies on the ability of

sites to recruit specific subsets of patients into Phase III trials. But without an effective patient recruitment and retention strategy to ensure the right number of eligible patients, trials risk failing before they have even started.

THE CHALLENGE OF DIVERSE PATIENT RECRUITMENT Recruiting targeted and diverse patient populations into clinical trials has never been more important to ensure robust efficacy and safety data. This is an issue the life science sector has struggled with for years; too often, older people, women, disabled people and those from under-represented ethnic groups are missing from clinical research. This was highlighted by the Sars-Cov-2 pandemic: despite statistics consistently showing that people from Black, Asian and minority ethnic communities were disproportionately affected by the virus, fewer than one percent of the 1,518 COVID-19 trials registered on ClinicalTrials.gov by June 2020 were collecting data on ethnicity2.

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The lack of diversity in research is problematic for the life science sector, but also for our global health. Between 2008 and 2013 around one in five newly approved drugs demonstrated differences in treatment response across ethnic groups leading, in some cases, to doctors prescribing drugs differently according to ethnicity3. Meanwhile, a 2020 study suggests women are nearly twice as likely as men to experience adverse reactions to therapies because drug dosages are traditionally based on clinical trials involving men4.

Reasons why certain groups have been continuously left out of research are complex: unconscious bias may play a part while research shows that cultural barriers and a lack of knowledge of clinical trials also contributes5. A lack of trust in healthcare systems, medical research and/ or pharmaceutical companies can also play a part. A recent study found that more than one in three (35.5%) of participants said they did not trust pharmaceutical companies6. While no data on ethnicity was recorded, the researchers did find that women and people with poor knowledge of their condition were more likely to distrust pharmaceutical companies, which could help to explain the under-representation of certain patient groups in industrysponsored trials.

While small steps have been taken over the years to address this, the growth of the personalised medicines market highlights a need for the industry to review its practices, become more patient-centric and commit to increasing the diversity of clinical trial participants. After all, if clinical trials for potential targeted therapeutics do not adequately represent the entire patient population in need of that specific treatment, how can we be sure it will work for everyone?

Potential treatments that target specific proteins or genetic mutations could have life-changing benefits for those who are eligible, but it inevitably means a smaller patient population from which to recruit people into Phase III trials, making recruitment more challenging. To achieve meaningful patient diversity in clinical trials, we, as an industry, must put patients’ needs first. This involves identifying who they are and what they do, and developing appropriate and targeted plans to reach and educate them.

By becoming more intentional in the way we approach and engage with patients, we can build relationships and trust across communities, helping to break down barriers and subsequently ensuring trials become fully representative of the patient population.

CLINICAL TRIAL DESIGN Effective patient recruitment begins with putting the patient perspective at the heart of clinical trial design. Studies should be built around patients’ needs and not just the treatment being investigated. A trial that has considered the challenges patients face and makes it as easy as possible for them to take part will find recruitment and retention a smoother process.

PATIENT-CENTRIC MATERIALS Patient-centricity also plays a key role in the development of patient materials. Too often, information is not presented in a way that engages with the intended patient population: it may not be in the most appropriate format or language, for example. Materials may also be lacking vital details that patients will want to know about, such as how many visits to the clinic will be necessary, if there are any associated costs involved and whether monitoring can be done at home.

ADDRESSING PATIENT DIVERSITY IN CLINICAL TRIALS

COMMUNITY ENGAGEMENT

Diversity in clinical trials is an issue that the industry is consciously aware of and trying to solve, but action can often be slow. The development of personalised medicines requires solutions now.

Identifying and reaching eligible patients is not just about finding them in the clinic. Working with clinicians is a crucial part of patient recruitment for clinical trials, but so too is community engagement. Visiting communities where

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people live and work, and engaging with trusted community groups, leaders and healthcare professionals can often be a more effective tactic for patient recruitment, particularly for underrepresented ethnic groups.

TIME It is often the case that clinical trial sites are under pressure to meet patient recruitment deadlines. A side effect of this is that patients can feel rushed into deciding whether or not to participate. It is important to remember that patients are people, and clinical trial participation can seem daunting.

Allowing individuals time to come to a decision will result in more confident and engaged participants, especially when they also have access to patient-centric study information.

In many cases this can help sites reach recruitment milestones more quickly.

TRUSTED VENDORS Patient recruitment is a big task for any trial, but particularly for personalised medicines due to the smaller pool of eligible patients. Successful recruitment for these targeted therapies can therefore be more challenging. Working in partnership with an experienced vendor will enable the development and implementation of targeted and bespoke recruitment and retention strategies to ensure the right patients are recruited in adequate numbers within specified deadlines, giving trials the best chance of reaching their identified endpoints. In some cases, patient recruitment can be accelerated resulting in trial recruitment closing ahead of schedule. This not only reduces costs for trial sponsors, but will ultimately help get life-changing drugs to patients more quickly.

The growth of the personalised medicine market heralds new possibilities in healthcare, especially for those with rare and complex conditions. While diversity in research has always been a challenge for the sector, the rise of targeted therapies is necessitating a change in patient recruitment practices to ensure trials become more inclusive and representative of specific patient populations.

Strategies that put patients firmly at the heart of clinical trials will not only help to unlock the powerful potential of personalised medicines, but will begin to change the patient recruitment landscape of clinical trials as a whole.

About Kate Shaw Kate Shaw is the founder and CEO of Innovative Trials, a UK-based clinical trials patient recruitment company, and has more than 20 years’ experience in patient recruitment support for clinical research. Her company has worked with pharmaceutical companies on nearly 200 clinical trials, recruited around 40,000 people into clinical research and played a role in six new treatments being approved for patients across the world. For more information, visit innovativetrials.com

“To achieve meaningful patient diversity in clinical trials, we, as an industry, must put patients’ needs first.”

REFERENCE NOTES 1 - Grand View Research, Personalized Medicine Market Size, Share & Trends Analysis Report By Product (Personalized Medical Care, Personalized Nutrition & Wellness, DTC Diagnostics, Telemedicine, Complementary Medicine), And Segment Forecasts, 2021 - 2028, 2021 https://www.grandviewresearch.com/industry-analysis/ personalized-medicine-market 2 - Pan D, Sze S, Minhas JS. The impact of ethnicity on clinical outcomes in COVID-19: a systematic review. EClinicalMedicine. 2020 doi: 10.1016/j.eclinm.2020.100404. published online June 3 https://doi.org/10.1016/j.eclinm.2020.100404 3 - A Ramamoorthy, MA Pacanowski, J Bull, L Zhang (2014). Racial/ethnic differences in drug disposition and response: Review of recently approved drugs. Clinical Pharmacology & Therapeutics. Doi: https://doi.org/10.1002/cpt.61

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4 - Zucker, I., Prendergast, B.J. Sex differences in pharmacokinetics predict adverse drug reactions in women. Biol Sex Differ 11, 32 (2020). Doi: https://doi.org/10.1186/ s13293-020-00308-5 5 - RP Symonds et al. Recruitment of ethnic minorities into cancer clinical trials: experience from the front lines. British Journal of Cancer. 2012. 107(7): 1017–1021.

Doi: 10.1038/bjc.2012.240 6 - Pahus, L., Suehs, C.M., Halimi, L. et al. Patient distrust in pharmaceutical companies: an explanation for women under-representation in respiratory clinical trials?. BMC Med Ethics 21, 72 (2020). https://doi.org/10.1186/s12910-020-00509-y

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| news |

Putting the diverse into neurodiversity The global Institute Of Neurodiversity ION has launched its UK chapter.

The Institute aims to give a global voice to all neurodiverse groups, and ensure neurodivergent individuals are understood, represented, and valued equally in society.

Currently, 1 in 7 people in the UK are neurodiverse, living with conditions such as autism, ADHD, dyspraxia, dyslexia, dyscalculia, dysgraphia and Tourette syndrome.

Neurodiversity has long been regarded as something to ‘overcome’ or assimilate, a view ION seeks to challenge. The Institute intends to lobby government, industry, education and charity sectors, to promote a greater understanding of the reality of being neurodiverse and to work toward eliminating institutional discrimination.

Founded by former Chair of the Institute of Directors and governance expert Charlotte Valeur, with a global steering group of neurodivergent individuals and allies, the Institute Of Neurodiversity ION is based in Geneva, Switzerland. It is the world’s only umbrella organisation representing all neurodiverse groups, and aims to have one million members by 2025.

Some immediate tasks include challenging research programmes on neurodiverse groups by highlighting the unintended, future consequences that research may have. Another is to call for reform to common conversion therapies that aim to ‘cure’ neurodiversity, but have misguided aims of changing an individual to be different to what they naturally are.

Ms Valeur said: “We’re a vertical slice of society – in all colours, cultures, industries, countries, we are doctors, we are cleaners, we are everywhere.”

Ms Valeur has had a 35-year career in financial services and the broader corporate world as a non-executive director.

While at the Institute of Directors, she revealed in an interview with The Independent that she was autistic, a move that sparked a national conversation about workplace neurodiversity at the time.

She added: “Neurodiverse individuals all have different ways of thinking that have value. The route to equality for us all is not through making society comfortable with our existence, it is to educate society into breaking down those barriers and being inclusive of all types of viewpoints in the world.”

WHAT IS NEURODIVERSITY? Humans are hugely diverse in many ways, and neurodiversity (ND) is a form of diversity. Neurodiverse groups include ADHD, autism, dyspraxia, dyslexia, dyscalculia, dysgraphia, and Tourette syndrome. People who are ‘neurotypical’ are those whose brain works in the way that society expects.

Neurodiversity describes these natural variations in the human brain, which affect sociability, learning, attention, and mood. Judy Singer, the sociologist, coined the term in 1998 and journalist Harvey Blume helped to popularise the word.

The medical profession groups neurodiverse people into diagnostic conditions to help understand the challenges that people may experience. However, everyone’s different, even within neurodiverse types.

“Neurodiversity describes these natural variations in the human brain, which affect sociability, learning, attention, and mood.”

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A reconstruction of the penis worm Eximipriapulus inhabiting a hyolith shell.

penis worms were the first ‘hermits’ Ancient penis worms (Priapulida) invented the ‘hermit’ lifestyle some 500 million years ago, at the rise of the earliest animal ecosystems in the Cambrian period.

Hermit crabs are well known for employing snail shells as shelters against predators, but researchers have now found that penis worms invented the ‘hermit’ lifestyle hundreds of million years before hermit crabs first evolved.

Researchers studied collections of the Guanshan fossil deposits – famous because they preserve soft tissue (such as the bodies of worms) alongside the shelly material that makes up the conventional fossil record.

Four specimens of the penis worm Eximipriapulus were found inside conical shells of hyoliths, a long-extinct fossil group.

“The worms are always sitting snugly within these same types of shells, in the same position and orientation”, explained Dr Martin Smith, co-author of the study.

The researchers established that Cambrian predators were plentiful and aggressive, forcing the penis worms to take permanent shelter in empty shells.

Dr Smith added: “The only explanation that made sense was that these shells were their homes – something that came as a real surprise. Not long before these organisms existed, there was nothing alive more complex than seaweeds or jellyfish: so it’s mind-boggling that we start to see the complex and dangerous ecologies usually associated with much younger geological periods so soon after the first complex animals arrive on the scene.”

The research indicates the key role of predators in shaping ecology and behaviour in the very early stages of animal

evolution. Study findings will be published in the journal Current Biology.

A “hermiting” lifestyle has never been documented or observed in living or fossil penis worms; nor has it been directly observed in any organism living earlier than the ‘Mesozoic Marine Revolution’ in the age of dinosaurs.

The fact that it evolved independently in the immediate aftermath of the “Cambrian explosion”, which marked the rapid rise of modern animal body plans, highlights the remarkable speed and flexibility of the evolutionary process.

The study was carried out by researchers from Durham University and Yunnan University.

“The research indicates the key role of predators in shaping ecology and behaviour in the very early stages of animal evolution.”

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3d meat

ta e m d 3 Sizzling breakthrough for 3D meat A 4oz steak has been ‘lab-grown’ using a digital design file.

Israeli firm MeaTech 3D Ltd. cultivated the bio-printed steak using real fat and muscle cells. The cells were produced using an advanced process that starts by isolating ethically harvested bovine stem cells from living tissue samples and multiplying them.

Once cellular mass was reached, the structures of the stem cells were formulated into bio-inks compatible with MeaTech’s 3D bio-printer. The printed product was placed in an incubator to mature, where the stem cells were differentiated into fat and muscle cells to develop into fat and muscle tissue, thus forming the steak.

The meat is said to look, taste, smell and feel like the farmed variety.

MeaTech believes this breakthrough will revolutionise farming, as a replacement for conventional steak that maximises cell-based content rather than non-meat ingredients. The steak comprises real, living muscle and fat cells, and doesn’t contain any soy or pea protein typically used in plant-based alternatives.

The firm is now looking to improve its bioprinting and cultivation technologies to produce a sustainable source of cultivated meat that mirrors the key characteristics of farm-raised, premium steak.

The hope is also that it will simplify meat production and the supply chain. Current farming methods account for nearly 15 per cent of greenhouse gas emissions, making livestock-rearing a huge contribution to climate change.

The process for cultivated steak is also a fraction of the time for a conventional steak, which takes 18 months to reach the market. It is designed as ‘clean meat’ without the same bacterial contamination risk which typically causes spoilage, so is anticipated to have a longer shelf life. The process is also fully automated.

MeaTech is also developing advanced technologies to produce cell-based alternative protein products, including cell lines for beef, pork and chicken.

“MeaTech believes this breakthrough will revolutionise farming, as a replacement for conventional steak that maximises cellbased content rather than non-meat ingredients.”

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‘Super jelly’ can survive being run over by a car Researchers have developed a jelly-like material that can withstand the equivalent of an elephant standing on it, and completely recover to its original shape, even though it’s 80 per cent water.

The soft-yet-strong material, developed by a team at the University of Cambridge, looks and feels like a squishy jelly, but acts like an ultra-hard, shatterproof glass when compressed, despite its high water content.

The non-water portion of the material is a network of polymers held together by reversible on/off interactions that control the material’s mechanical properties. This is the first time that such significant resistance to compression has been incorporated into a soft material.

The ‘super jelly’ could be used for a wide range of potential applications, including soft robotics, bioelectronics or even as a cartilage replacement for biomedical use. The results are reported in the journal Nature Materials.

The way materials behave – whether they’re soft or firm, brittle or strong – is dependent upon their molecular structure. Stretchy, rubber-like hydrogels have lots of interesting properties that make them a popular subject of research – such as their toughness and self-healing capabilities – but making hydrogels that can withstand being compressed without getting crushed is a challenge.

“In order to make materials with the mechanical properties we want, we use crosslinkers, where two molecules are joined through a chemical bond,” said Dr Zehuan Huang from the Yusuf Hamied Department of Chemistry, the study’s first author. “We use reversible crosslinkers to make soft and stretchy hydrogels, but making a hard and compressible hydrogel is difficult and designing a material with these properties is completely counterintuitive.”

Working in the lab of Professor Oren A Scherman, who led the research, the team used barrel-shaped molecules called cucurbiturils to make a hydrogel that can withstand compression. The cucurbituril is the crosslinking molecule that holds two guest molecules in its cavity – like a molecular handcuff. The researchers designed guest molecules that prefer to stay inside the cavity for longer than normal, which keeps the polymer network tightly linked, allowing for it to withstand compression.

“At 80% water content, you’d think it would burst apart like a water balloon, but it doesn’t: it stays intact and withstands huge compressive forces,” said Scherman, Director of the University’s Melville Laboratory for Polymer Synthesis. “The properties of the hydrogel are seemingly at odds with each other.”

“The way the hydrogel can withstand compression was surprising, it wasn’t like anything we’ve seen in hydrogels,” said co-author Dr Jade McCune, also from the Department of Chemistry. “We also found that the compressive strength could be easily controlled through simply changing the chemical structure of the guest molecule inside the handcuff.”

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To make their glass-like hydrogels, the team chose specific guest molecules for the handcuff. Altering the molecular structure of guest molecules within the handcuff allowed the dynamics of the material to ‘slow down’ considerably, with the mechanical performance of the final hydrogel ranging from rubber-like to glasslike states.

“People have spent years making rubber-like hydrogels, but that’s just half of the picture,” said Scherman. “We’ve revisited traditional polymer physics and created a new class of materials that span the whole range of material properties from rubber-like to glass-like, completing the full picture.”

The researchers used the material to make a hydrogel pressure sensor for real-time monitoring of human motions, including standing, walking and jumping.

“To the best of our knowledge, this is the first time that glass-like hydrogels have been made. We’re not just writing something new into the textbooks, which is really exciting, but we’re opening a new chapter in the area of high-performance soft materials,” said Huang.

Researchers from the Scherman lab are currently working to further develop these glass-like materials towards biomedical and bioelectronic applications in collaboration with experts from engineering and materials science. The research was funded in part by the Leverhulme Trust and a Marie Skłodowska-Curie Fellowship. Oren Scherman is a Fellow of Jesus College.

REFERENCE: Zehuan Huang et al. ‘Highly compressible glass-like supramolecular polymer networks.’ Nature Materials (2021). DOI: 10.1038/s41563-021-01124-x

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New microscope uses photonics for insights into ‘superbugs’ Scientists are building a new super-resolution microscope that uses laser light to study the inner workings and behaviours of superbugs to gain new insights into how they cause disease.

The microscope will allow scientists to peer into bacteria like at a molecular-scale resolution – showing up objects smaller than 10,000th the thickness of a sheet of paper.

A leading cause of bacterial pneumonia, meningitis, and sepsis, Streptococcus Pneumoniae bacteria are estimated to have killed around 335,000 children aged five years and under in 2015 worldwide.

Current technologies do not allow a resolution that enables thorough studies of bacterial properties that affect disease development.

fluorescence NANOscopy and VIBrational microscopy’ (or ‘NanoVIB’ for short), the project will shed new light on how superbugs can cause disease, thereby providing the basis for the development of new antimicrobials to treat bacterial infections.

The European Commission has granted €5,635,529 via the Photonics Public Private Partnership to build the microscope.

TEN-FOLD RESOLUTION

The super-resolution microscope uses laser light to illuminate proteins at very high resolutions, allowing scientists to gain new insights into what makes these potentially deadly bacteria so pathogenic.

While super-resolution microscopes already exist, the NanoVIB team proposes to make a new device with unrivalled resolution capable of revealing the intricate, detailed molecular mechanisms underlying inter-and intracellular processes and disease.

Although electron microscopes can show minute detail at the atomic level, they cannot analyse live specimens: electrons can easily be deflected by molecules in the air, meaning any bacteria under inspection must be held in a vacuum. Super-resolution microscopes are far more superior for biological analysis.

Project coordinator, Professor Jerker Widengren, said: "We expect our new microscope prototype to be a nextgeneration super-resolution system, making it possible to image cellular proteins marked with fluorescence emitters (fluorophores) with a ten-fold higher resolution than with any other fluorescence microscopy technique.

Called the ‘NANO-scale Visualisation to understand Bacterial virulence and invasiveness - based on

“With the help of advanced laser, detector and microscopy technologies that will be developed in the project, super-

32

| BIOSCIENCE TODAY |

| news |

resolution localisation patterns of specific proteins will be overlaid with light-scattering images, correlating these patterns with local structures and chemical conditions in the bacteria.

“Using laser light, this new microscope will show how bacterial proteins localise on the surface of bacteria, allowing scientists to study the interaction of the pathogen with immune and host cells.

It works based on the so-called MINFLUX concept, where infrared laser light excites fluorophore-labelled molecules in a triangulated manner – leading to an increased resolution.

The user can then fine-tune the microscopic imaging to previously unimaginable resolutions.

“MINFLUX microscopy will make it possible to resolve how certain pneumococcal surface proteins are distributed on the bacteria under different cell division stages, and

whether these proteins are localised in such a way that specific, extra sensitive surface regions of the bacteria, a critical step of the cell division, are protected from immune activation,” said Widengren.

“The super-resolution microscope uses laser light to illuminate proteins at very high resolutions, allowing scientists to gain new insights into what makes these potentially deadly bacteria so pathogenic.”

Teaching old oaks new tricks Mature oak trees will increase their rate of photosynthesis by up to a third in response to the raised CO2 levels expected to be the world average by about 2050, new research shows.

The results, published in Tree Physiology, are the first to emerge from a giant outdoor experiment, led by the University of Birmingham in which an old oak forest is bathed in elevated levels of CO2. Over the first three years of a ten-year project, the 175-year-old oaks clearly responded to the CO2 by consistently increasing their rate of photosynthesis.

Researchers are now measuring leaves, wood, roots, and soil to find out where the extra carbon captured ends up and for how long it stays locked up in the forest.

The increase in photosynthesis was greatest in strong sunlight. The overall balance of key nutrient elements carbon and nitrogen did not change in the leaves. Keeping the carbon to nitrogen ratio constant suggests that the old trees have found ways of redirecting their elements, or found ways of bringing more nitrogen in from the soil to balance the carbon they are gaining from the air.

The research was carried out at the Free-Air CO2 (FACE) facility of the Birmingham Institute of Forest Research (BIFoR) in close collaboration with colleagues from Western Sydney University who run a very similar experiment in old eucalyptus forest (EucFACE). BIFoR FACE and EucFACE are the world’s two largest experiments investigating the effect of global change on nature.

Birmingham researcher Anna Gardner, who carried out the measurements, said: “I’m really excited to contribute the first published science results to BIFoR FACE, an experiment of global importance. It was hard work conducting measurements at the top of a 25m oak day after day, but it was the only way to be sure how much extra the trees were photosynthesising.”

Professor David Ellsworth, EucFACE lead scientist, said

33

Anna Gardner, from the University of Birmingham, hard at work in the treetops.

“Previous work at EucFACE measured photosynthesis increased by up to a fifth in increased carbon dioxide. So, we now know how old forest responds in the warm-temperate climate that we have here in Sydney, and the mild temperate climate of the northern middle latitudes where Birmingham sits. At EucFACE we found no additional growth in higher CO2, and it remains to be seen if that will be the case for BIFOR as well.”

Professor Rob MacKenzie, founding Director of BIFoR,added: “It’s a delight to see the first piece of the carbon jigsaw for BIFoR FACE fall into place. We are sure now that the old trees are responding to future carbon dioxide levels. How the entire forest ecosystem responds is a much bigger question requiring many more detailed investigations. We are now pushing ahead with those investigations.”

| BIOSCIENCE TODAY |

| news |

Spider web secrets unravelled American scientists are the first to document every step of web-building.

Johns Hopkins University researchers discovered precisely how spiders build webs by using night vision and artificial intelligence to track and record every movement of all eight legs as spiders worked in the dark.

Their creation of a web-building playbook or algorithm brings new understanding of how creatures with brains a fraction of the size of a human’s are able to create structures of such elegance, complexity and geometric precision. The findings are now available online.

Behavioural biologist and senior author Andrew Gordus said: “I first got interested in this topic while I was out birding with my son. After seeing a spectacular web I thought, ‘if you went to a zoo and saw a chimpanzee building this you’d think that’s one amazing and impressive chimpanzee.’ Well this is even more amazing because a spider’s brain is so tiny and I was frustrated that we didn’t know more about how this remarkable behavior occurs.”

“Even if you video record it, that’s a lot of legs to track, over a long time, across many individuals,” said lead author Abel Corver, a graduate student studying web-making and neurophysiology. “It’s just too much to go through every frame and annotate the leg points by hand so we trained machine vision software to detect the posture of the spider, frame by frame, so we could document everything the legs do to build an entire web.”

They found that web-making behaviors are quite similar across spiders, so much so that the researchers were able to predict the part of a web a spider was working on just from seeing the position of a leg.

“Even if the final structure is a little different, the rules they use to build the web are the same,” Gordus said. “They’re all using the same rules, which confirms the rules are encoded in their brains. Now we want to know how those rules are encoded at the level of neurons.”

“Now we’ve defined the entire choreography for web building, which has never been done for any animal architecture at this fine of a resolution.”

Future work for the lab includes experiments with mindaltering drugs to determine which circuits in the spider’s brain are responsible for the various stages of web-building.

Web-weaving spiders that build blindly using only the sense of touch, have fascinated humans for centuries. Not all spiders build webs but those that do are among a subset of animal species known for their architectural creations, like nest-building birds and puffer fish that create elaborate sand circles when mating.

“The spider is fascinating,” Corver said, “because here you have an animal with a brain built on the same fundamental building blocks as our own, and this work could give us hints on how we can understand larger brain systems, including humans, and I think that’s very exciting.

The first step to understanding how the relatively small brains of these animal architects support their high-level construction projects, is to systematically document and analyse the behaviours and motor skills involved, which until now has never been done, mainly because of the challenges of capturing and recording the actions, Gordus said.

His team studied a hackled orb weaver, a spider native to the western United States that’s small enough to sit comfortably on a fingertip. To observe the spiders during their night-time web-building work, the lab designed an arena with infrared cameras and infrared lights. With that set-up they monitored and recorded six spiders every night as they constructed webs, tracking the millions of individual leg actions with machine vision software designed specifically to detect limb movement.

Authors also include Nicholas Wilkerson, a former Hopkins undergraduate and current graduate student at Atlantic Veterinary College, and Jeremy Miller, a graduate student at Johns Hopkins. The work was supported by the National Science Foundation Graduate Research Fellowship Program and National Institutes of Health grant R35GM124883.

“Future work for the lab includes experiments with mind-altering drugs to determine which circuits in the spider’s brain are responsible for the various stages of web-building.”

34

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Re

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Ir

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80

49

In

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N

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O

32

112

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Ge 72.64

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204.3833

113

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Pb

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2 8 18 18 4

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207.2

114

Fl (289)

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2 8 18 28 8 2

67

98

Ho

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68

Mc (288)

Flerovium

164.93032

Er 167.259

Holmium 2 8 18 32 28 8 2

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69

Tm

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101

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116

102

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71

2 8 18 32 32 8 2

103

Lu

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85

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I

At

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86

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117

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39.948

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126.90447

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53

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173.054

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2 8 18 32 30 8 2

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168.93421

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84

Ar

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127.6

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Neon

18

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Tellurium

208.9804

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20.1797

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35.453

Se

52

Ne

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Chlorine 2 8 18 6

78.96

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121.76

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10

Fluorine

Sulfur 34

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18.9984032

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Antimony

Lead 2 8 18 32 32 18 3

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74.9216

Tin

2 8 18 32 18 3

16

Arsenic

118.71

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30.973762

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15.9994

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Cd

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48

196.966569

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Zinc

Silver

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192.217

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12.0107

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Copper

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63.546

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58.6934

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101.07

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58.933195

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186.207

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144.242

U

Co

Iron

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55.845

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47.867

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137.327

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87.62

132.9054

87

Ti

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44.955912

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