Cambridge scientists believe that a steroid discovered in the 1990s in dogfish sharks could lead to potential treatments for Parkinson’s Disease.

Initial research suggest that squalamine could be exploited in various ways as the basis of a new therapeutic. 

The compound has previously been used in clinical trials for cancer and eye conditions in the US and a trial in Parkinson’s Disease patients is now being planned by one of the researchers involved in the study.

While squalamine was discovered in dogfish sharks it is impossible to derive any medical benefits from shark tissue and the form used by scientists is a safer and more reliable synthetic analogue. To date, it has been extensively investigated as a potential anti-infective and anticancer therapy.

But in the new study, researchers discovered that squalamine also dramatically inhibits the early formation of toxic aggregates of the protein alpha-synuclein – a process thought to start a chain reaction of molecular events eventually leading to Parkinson’s. They also found that it can suppress the toxicity of these poisonous particles.

While their findings only represent a step towards a treatment for Parkinson’s Disease in humans, they described the results as representing significant progress.

The study was led by academics from the Centre for Misfolding Diseases, based in the Chemistry Department at the University of Cambridge, UK, and Georgetown University and the National Institutes of Health in the United States. Scientists from the Netherlands, Italy and Spain also played key roles.

The researchers tested squalamine in both cell cultures in the lab, and in an animal model using nematode worms. While their findings therefore only represent a step towards a treatment for Parkinson’s Disease in humans, they described the results as representing significant progress.

The findings are published in Proceedings of The National Academy of Sciences.

Professor Christopher Dobson, one of the authors and a Professor in the Chemistry Department at the University of Cambridge, said: “To our surprise, we found evidence that squalamine not only slows down the formation of the toxins associated with Parkinson’s Disease, but also makes them less toxic altogether.”

“If further tests prove to be successful, it is possible that a drug treating at least some of the symptoms of Parkinson’s Disease could be developed from squalamine. We might then be able to improve on that incrementally, by searching for better molecules that augment its effects.”

Co-author, Professor Michele Vendruscolo, from the Department of Chemistry at the University of Cambridge added: “Squalamine can prevent alpha-synuclein from malfunctioning, essentially by normalising its binding to lipid membranes. If there are going to be ways to beat the disease, it seems likely that this is one that may work.”

The study stemmed from research led by Dr Michael Zasloff, professor of surgery and pediatrics at Georgetown University School of Medicine in the US. Zasloff, who also co-authored the latest study, discovered squalamine in 1993 and has since led extensive work exploring its potential as a treatment for conditions including cancer.

In the new study, researchers explored squalamine’s capacity to displace alpha-synuclein from cell membranes – a phenomenon that was first observed in the laboratory headed by another co-author, Dr Ad Bax, in the National Institutes of Health in Bethesda, USA. This finding has significant implications for Parkinson’s Disease, as alpha-synuclein works by binding to the membranes of tiny, bubble-like structures called synaptic vesicles, which help to transfer neurotransmitters between neurons.

Under normal circumstances, the protein aids the effective flow of chemical signals, but in some instances, it malfunctions and instead begins to clump together, creating toxic particles harmful to brain cells. This clustering is the hallmark of Parkinson’s Disease.

The researchers carried out a series of experiments which analysed the interaction between squalamine, alpha-synuclein and lipid vesicles, building on earlier work from Cambridge scientists which showed the vital role that vesicles play in initiating the aggregation. They found that squalamine inhibits the aggregation of the protein by competing for binding sites on the surfaces of synthetic vesicles. By displacing the protein in this way, it significantly reduces the rate at which toxic particles form.

Further tests, carried out with human neuronal cells, revealed  that squalamine also suppresses the toxicity of these particles.

Finally, the group tested the impact of squalamine in an animal model of Parkinson’s Disease, by using nematode worms genetically programmed to over-express alpha-synuclein in their muscle cells. As the worms develop, alpha-synuclein aggregation causes them to become paralysed, but squalamine prevented the paralysis from taking effect. 

“We could literally see that the oral treatment of squalamine did not allow alpha-synuclein to cluster, and prevented muscular paralysis inside the worms,” Zasloff said.

Zasloff is now planning a clinical trial with squalamine in Parkinson’s Disease patients in the US.

Further research is needed to determine the precise benefits of squalamine – and what form any resulting drug might take. It is not yet clear whether squalamine can reach the specific regions of the brain where the main molecular processes determining Parkinson’s Disease take place.

The researchers suggest it would be interesting to start investigating the efficacy of squalamine as a means to alleviate certain symptoms. If taken orally, for instance, they believe the compound could relieve the severe constipation many patients experience, by targeting the gastrointestinal system and affecting alpha-synuclein in the gut. A treatment of that sort could “cascade” signals to other parts of the body.

“Targeting alpha-synuclein in the gut may perhaps in some cases be sufficient to delay the progress of other aspects of Parkinson’s Disease, at least for symptoms concerning the peripheral nervous system,” Vendruscolo said.

“In many ways squalamine gives us a lead rather than a definitive treatment,” Professor Dobson added: “Parkinson’s Disease has many symptoms and we hope that either this compound, or a derivative of it with a similar mechanism of action, could alleviate at least some of them. One of the most exciting prospects is that, subject to further tests, we might be able to use it to make improvements to patients’ lives, while also studying other compounds with the aim of developing a more powerful treatment in the future.”

• PHOTOGRAPH SHOWS: Professor Christopher Dobson

Cambridge Enterprise and the University of Cambridge Enterprise Fund, managed by Parkwalk, have invested £500k in Polypharmakos Limited, a spin-out from the university and the Royal Botanic Gardens, Kew.

Polypharmakos’ mission is to screen natural-product sources of plant, fungal and insect origin for antimicrobially active substances with novel mechanisms of action and to develop them to address the emerging global antimicrobial resistance (AMR) crisis.

Founded in 2016 by Dr John Normanton and Tom Sopwith of ArgantriX Ltd., Polypharmakos arose from discussions with Prof Duncan Maskell (Marks & Spencer Professor of Farm Animal Health, Food Science and Food Safety) and Prof Monique Simmonds (deputy director of science, Royal Botanic Gardens, Kew).

The company undertook a small Cambridge Enterprise-funded pilot screening exercise in 2016 in conjunction with the teams of Prof Clare Bryant (University of Cambridge, Professor of Innate Immunity) and Dr Mark Holmes (University of Cambridge, Reader in Microbial Genomics and Veterinary Science).

The project revealed a number of active substances in a small sample of intelligently selected extracts, indicating that the Kew collections should be an ideal starting source for new antimicrobials.

In addition, the Company received pilot project funding from Swansea University and Swansea Innovations for the structural characterisation of Seraticin®, a maggot-derived, small molecular weight, broad spectrum antimicrobial.

Dr Normanton, CEO of Polypharmakos, said: “The funding will launch the company into full operation and begin this exciting venture with core collaborations with Cambridge and RBG Kew.

“Coupling the synergistic expertise within RBG Kew in the selection and characterisation of medicinal leads from natural products in its collections with the skills of the Cambridge University team in antibacterial modes of action and modulation of innate immunity will open an exciting new chapter in the hunt for new drugs useful against AMR pathogens.”

Prof Monique Simmonds, RBG Kew, added: “Funding from Polypharmakos provides Kew with an exciting opportunity to work with scientists at Cambridge to re-evaluate plant and fungal diversity for new antibiotic leads to support human and animal health.

“The project utilises our increased knowledge about plant and fungal chemistry as well as targets for new drugs.”

Polypharmakos was supported through this fundraising by legal advisers, Greenaway Scott and taxation specialists, James Cowper Kreston.

• PHOTOGRAPH SHOWS: The Palm House at Kew. Credit – RGB Kew

According to research from our data team, office occupiers who spend three quarters of a million pounds a year on office space in Cambridge can afford more than three times the amount of space than in London’s West End.

£750k a year is the typical amount of rent paid by medium-sized businesses with a turnover of around £5-10 million in London and the South East. This annual sum secures just 6,000 sq ft in Mayfair, compared to 20,548 sq ft in Cambridge, ranked ninth out of 24 office hub locations in terms of affordability.

In London, sky high rents and lack of the right kind of space is increasingly causing businesses to question the need to retain all their functions in the capital, and our city undoubtedly benefits from this.

However, in our list of 24 office hub locations there are a number which are in fact closer to London, such as Reading and Watford, where businesses could get even more bang for their buck than in Cambridge: highlighting that simply finding good value space isn’t enough.

In Reading, businesses could obtain 20,833 sq ft for the same amount and in Watford they could rent 27,273 sq ft.

I would suggest then that what our list really highlights is the value for money that Cambridge provides business. It’s not the cheapest option but – let’s face it – the best option rarely is.

That’s because, as I keep saying, achieving the right space for a business requires much more than just renting a floor and four walls. A number of factors should be taken into account including staff retention/attraction, infrastructure and the location itself in terms of proximity to and for clients and, quite simply, whether it’s a nice place to spend the best part of your day. For many is seems that Cambridge, at the moment, is hitting the sweet spot.

Yes, cheaper space can be found elsewhere, but these locations can rarely challenge the ready-made talent pool that is found in the city. Cambridge’s business and science parks, and increasingly its city centre, attract both locally grown and global science, technology and commercial businesses, keen to tap into the exceptional wealth of talent that we have in the county. Established park occupiers on the periphery of the city complement businesses in the centre that are looking for a different type of space in the heart of a bustling and beautiful city. Luckily in Cambridge we can provide for both. The key however is to ensure that we can continue to do this while evolving with a changing business environment.

Over the last 10 years, ways of working have changed dramatically. In London, operators have responded to landlords by providing co-working space, which is now a firmly established trend in the capital.

This type of operation is predicted to take-off in Cambridge and should help attract other types of occupiers, such as small start-ups, to the city. While this is a ringing endorsement and will benefit the city, the worry is accommodating them.

There are a number of new development sites being brought forward, such as on Station Road, but there is a finite amount of space. As we all know, a lack of quality stock combined with high demand will often put an upward pressure on rents.

While this may benefit landlords, outpricing occupiers is rarely good for business hubs, particularly those like ours which thrives on its eclectic mix of businesses. In fact, when we come to review our list of locations and office affordability in 10 years’ time, I hope Cambridge is still providing exceptional value for money. How we achieve this, however, is the real question.

Can things possibly get any worse than they did in 2016? No, don’t answer that!

The year was full of, mostly, unwelcome surprises: the Referendum outcome and the undiminished in-fighting over its execution; the ominous triumph of Trump (regardless of the ‘Trump Bump’) and the insidious influence of Putin; the clay feet of Teresa May’s ‘iron lady’ as we face a winter of discontent to rival the three-day week of the 1970s; and the passing of celebrities like David Bowie, Mohammed Ali, Leonard Cohen, George Michael and Zsa Zsa Gabor. You’re well out of it guys and gals, believe me!

Still, you’ve got to believe in better, as they say over at Sky TV, or at least keep buggering on as Sir Winston Churchill said during the dark days of World War II.

Back then it was the Spirit of the Blitz that saw us through, a consciousness that we’re all in this together, and a similar unity of purpose would serve all those of us in business well right now.

To take the optimistic view, I believe the current state of affairs is because, on the home front at least, we are betwixt and between: so long as the whole Brexit issue hangs fire business will continue to be cautious and irresolute.

But once the terms of Brexit have been agreed (yeah, I know) and Article 50 has been triggered (at least there appears to be a consensus that this will take place in March) we can stop arguing about how we’re going to do it and get on with doing it.

Although, along with most of the ad industry, I would have preferred to remain in the Single Market (easy access to 500 million brains being preferable to only being able to easily employing those in the UK), history cannot be rewritten and prevaricating just exacerbates the problem. 

Europe has its own problems anyway; what with the rise of the far right, the disillusionment felt by whole swathes of the population with both their own political classes and the grand European project as a whole, and seemingly every bank from Frankfurt to Siena in a spot of bother, we might just be able to make the best of the people having spoken.

Similarly, the outcome of the US presidential election and the ill-preparedness of our Foreign and Trade Ministries to anticipate it (and the ham-fisted approach to negotiations since) fills me with misgiving, but the fact remains that we’ve been presented with a fait accompli and we have to make the best of it.

And the prospects are not as dire as you might think, despite our own Government’s ineptness and Trump’s disastrous foreign policy (even before formal appointment he has contrived to give the Chinese a bloody nose!)  But love him or loathe him (and his pal Nigel Farage) the guy is well disposed to us and ready to put us at the front of the queue international trade wise, in contrast to the dismissive comments of the outgoing president, Barrack Obama.

So, onward and upward, forward and fearless!  Let’s leave behind Betwixit, embrace Brexit, and try for a better, happy and prosperous 2017!

A fresh surge of global business in the last quarter of 2016 took Cambridge cyber security business Darktrace to unprecedented trading heights.

The UK company said it had a “phenomenal” three months which has taken the value of contracts secured to date to more than $125 million. Its Enterprise Immune System technology, which detects and repels cyber attacks, has now been deployed over 2,000 times.

Now deployed in 60 countries, Darktrace has expanded into new territories including Bermuda, Luxembourg, Malaysia, Morocco and Portugal, adding to strong traction across the US, Canada, Europe and APAC. 

Customers include Blackhawk Network, BT, KEEN, Rakuten Securities Inc., the Church of England, Birmingham International Airport, Drax, Phoon Huat, Saniflo and Parchment.

Darktrace says its revenue is increasing by 600 per cent year on year and customer renewals at over 90 per cent. With over 360 employees across 23 global locations, the company has more than doubled in size over the last year.

The Enterprise Immune System is powered by unsupervised machine learning and mathematics developed by specialists from the University of Cambridge. By learning the ‘pattern of life’ for each user, device and network, the system automatically detects anomalous changes in behaviour and emerging threats. This self-learning technology has allowed Darktrace to discover over 27,000 serious cyber incidents, which went unnoticed by legacy security tools.

CEO Nicole Eagan (pictured) said: “Our outstanding growth this quarter reflects the huge demand for Darktrace’s self-learning solution, which is the only technology capable of catching in-progress attacks without prior warning or special insights. 

“Organisations of all sizes across the world are deploying the Enterprise Immune System to defend against not just today’s cyber-threats, but tomorrow’s, too.”

Global philanthropists Bill and Melinda Gates are investing $9 million in Cambridge antibody technology in a bid to accelerate development of vaccines and therapeutics to fight HIV and other infectious diseases. Their foundation is supporting a new research programme by Kymab over three years. It bids to leverage the Kymouse™ antibody platform developed by the UK business.

The Gates Foundation will have the rights to develop and distribute any end products to low-income countries. Kymab will retain the rights to commercialise the products in developed countries. The funding builds on Kymab’s established work, allowing the parties to further collaborate in the future.

Kymab CEO Dr David Chiswell said: “We are delighted that the Bill & Melinda Gates Foundation has extended our collaboration. We have built a strong infectious disease programme under Professor Paul Kellam, our vice-president of vaccines & infectious disease and we share the foundation’s aims to tackle diseases that have significant impact in some of the world’s poorest countries.

“We look forward to continuing to use our ability to produce human antibodies using our Kymouse™ technology to support and accelerate vaccine and therapeutic antibody development for global diseases.”

Professor Allan Bradley, Kymab’s chief technology officer, added: “It was always clear to me that the Kymouse™ was a valuable tool in the fight against infectious disease and this was also recognised very early by the Gates Foundation.

“Over the last two years we have worked with the Foundation to realise this ambition and their increased support is a fantastic recognition of Kymab’s continuing effort in testing vaccine candidates for infectious disease prevention and developing therapeutic antibodies for treatment.”

The extension of the collaboration with the Gates Foundation follows publication in Science last September of new findings which showed that Kymouse was an effective platform for discovering and testing novel vaccines and therapeutics for infectious diseases including HIV.

Kymab has been working with the Gates Foundation and its partners since 2014 on programmes in diseases such as malaria, HIV, and typhoid; together, these diseases result in more than one million deaths each year. 

In addition to the new investment in Kymab’s research, the Gates Foundation has also invested $30m in Kymab’s Series B and Series C funding rounds, which supported development of the Kymouse platform.

• PHOTOGRAPH SHOWS: Dr David Chiswell, CEO of Kymab

Cambridge, UK-based Owlstone Medical Ltd, a diagnostics company developing a breathalyzer for disease, has raised $11.55 million (£9.3m) in a funding round led by existing investors.

The cash will be used to commercially launch the company’s breath biomarker R&D services, including the opening of a new high volume clinical facility, and to fund ongoing clinical trials in lung and colon cancer screening. 

The funding follows the original investment of $7m (£4.9m) that spun Owlstone Medical out in June 2016.

Owlstone Medical is leveraging proprietary and proven Field Asymmetric Ion Mobility Spectrometry (FAIMS) technology in its disease breathalyzer product range. FAIMS measures volatile organic compound (VOC) metabolites in patient’s breath or bodily fluids which are specific to disease. Measurement of VOC biomarkers allows non-invasive diagnosis of disease at a very early stage, to enable more effective treatment and better patient outcomes.

Billy Boyle, co-founder and CEO at Owlstone Medical said: “Securing this funding is further validation of our FAIMS technology and breath biopsy as a new diagnostic modality. We’ve made fantastic progress in our LuCID lung cancer trial, which will recruit up to 3,000 patients across 21 sites in the UK and Europe, making it the world’s largest breath-based study ever undertaken for early cancer detection.  

“The commercial launch of our R&D services will, for the first time, allow clinical and pharma partners to easily identify breath biomarkers for novel diagnostics and precision medicine applications.”

Regius Professor Christofer Toumazou, advisor to Medtekwiz and Non-Executive Director of Owlstone Medical, said: “Owlstone Medical has made tremendous progress in clinical trials for the diagnosis of colon and lung cancer, which are two of the biggest cancer killers worldwide. I am delighted that with this additional investment we are a step closer to making breath biopsy a reality for patients.”

The potential of the technology to enable rapid detection of disease, without the need for costly, invasive medical procedures, has seen Owlstone Medical’s breath sampling and analysis technology recently named Invention of the Year in the 2017 Top 50 in Digital Health Awards. Hosted by Rock Health, Fenwick & West, Goldman Sachs, and Square 1 Bank in the run up to the J.P.Morgan Conference, the accolade recognises exceptional progress in bringing technological advancements to healthcare.

• PHOTOGRAPH SHOWS: Billy Boyle

Audio Analytic, a Cambridge UK Artificial Intelligence business addressing sound recognition technology, has closed a $5.5 million Series A round.

Cambridge Innovation Capital led the round, with IQ Capital, Rockspring, Cambridge Angels and Martlet participating.

The funding will enable the company to scale and meet growing Smart Home OEM demand for its Artificial Audio Intelligence software, ai3™.

“In the last two years, Smart Home device ownership has more than doubled,” said Stuart Sikes, President of research firm Parks Associates. “We estimate companies will sell almost 55 million smart home devices in 2020.”

Founded in 2008, Audio Analytic has pioneered the development and commercialisation of intelligent sound recognition using advanced machine learning. Its innovative ai3™ software enables devices to recognise significant sounds and take automated action.

Audio Analytic works with Smart Home original equipment manufacturers and chip companies, with a range of consumer devices containing ai3™ software already in the market and more slated to launch in 2017.

This Series A funding follows previous rounds in 2014 and 2015, bringing the company’s total money raised to $8 million. The new round will enable the company to scale to meet increasing customer demand – doubling its team to 50 employees within the next 12 months – and introduce new sound profiles and features to the growing ai3™ platform.

Victor Christou, CEO at Cambridge Innovation Capital, said: “Audio Analytic’s market traction over the past 18 months has been highly impressive in the rapidly growing smart home market. We’re delighted to lead this series A round and continue our support of one of the world’s most exciting AI companies.”

Dr Chris Mitchell, Audio Analytic’s founder and CEO, added: “At Audio Analytic we believe every sound tells a story, especially in the home. This $5.5m Series A round will enable us to meet growing customer demand for our Artificial Audio Intelligence and continue to develop the recognition of new sounds with the ai3™ platform.

“2017 promises to be the year of the Smart Home and AI – we are excited to be working with our customers right at the intersection of these two seismic industries.”

Audio Analytic is an official exhibitor at CES 2017 (5-8 January, Las Vegas) and will be demonstrating a range of new ai3™ sound profiles and features to customers and partners at the show.

A demonstration of sound recognition for the Smart Home using Audio Analytic’s ai3™ platform will also be available at the ARM booth (LVCC, South Hall 2 – MP25250) on invitation.