̽��ֱ�� of Cambridge - Jim Huntington

Academy of Medical Sciences announces 2018 Fellowships

cjb250 — Thu, 10 May 2018 10:22:09 +0000

̽��ֱ��new Fellows have been elected for their outstanding contributions to biomedical and health science, leading research discoveries, and translating developments into benefits for patients and the wider society.

This year's elected Fellows have expertise that spans sleep research, infectious and tropical diseases, diabetes medicine, parasite biology and ultrasound research and technology among many other fields.

Professor Sir Robert Lechler PMedSci, President of the Academy of Medical Sciences said: “ ̽��ֱ��Academy simply could not tackle major health and policy challenges without our dynamic and diligent brain trust of Fellows. I extend my warmest congratulations to all who are joining us this year, each of whom has earnt this prestige by advancing their own field of biomedical science.

“Later this year the Academy will celebrate 20 years of supporting the translation of biomedical and health research into benefits for society. As we celebrate this special anniversary we stand at a crossroads of both enormous health challenges and great opportunity for medical sciences. So I am delighted to see the remarkable breadth and depth of the expertise within our 48 new Fellows. We look forward to these experts joining us in addressing the health challenges we face head on and exploiting opportunities to improve health in the UK and internationally.”

̽��ֱ��Cambridge researchers among the new Fellows are:

Professor Simon Baron-Cohen FBA, Autism Research Centre
Professor Simon Griffin, Department of Public Health and Primary Care
Professor James Huntington, Cambridge Institute for Medical Research
Professor Peter Hutchinson, Department of Clinical Neurosciences
Professor Jonathan Mant, Department of Public Health and Primary Care
Professor Lalita Ramakrishnan, Department of Medicine
Professor David Rowitch, Department of Paediatrics
Professor Nicole Soranzo, Department of Haematology

̽��ֱ��new Fellows will be formally admitted to the Academy at a ceremony on 27 June 2018.

Eight Cambridge academics are among 48 of the UK’s world leading researchers who have been elected to join the prestigious Fellowship of the Academy of Medical Sciences.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Cambridge spin-out raises £7 million to develop treatments for lung disease

sc604 — Thu, 04 May 2017 15:57:10 +0000

̽��ֱ��company, Z Factor Limited, was founded by Professor Jim Huntington of the Cambridge Institute for Medical Research. ̽��ֱ��new funding has come from existing investor Medicxi, as well as Cambridge Innovation Capital and Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm.

Z Factor is developing new treatments for Alpha-1-Antitrypsin Deficiency (AATD). AATD, which is a significant cause of liver and lung disease, results from a defect in the gene encoding Alpha-1-antitrypsin, a type of protein. Individuals with two defective copies of the gene, making up around 1 in 2000 of the Western population, typically develop emphysema starting in their 30s. They are also at an increased risk of developing liver diseases such as cirrhosis and cancer. Around 2% of people have one defective copy of this gene, and are at five-fold increased risk of developing Chronic Obstructive Pulmonary Disease (COPD) as they age.

̽��ֱ��most common mutation causing AATD is called the Z mutation, which disrupts the normal folding of the protein. Professor Huntington and his team obtained the crystallographic structure of this mutant form of Alpha-1-antitrypsin, which allowed for the first time the rational design of drugs that could correct folding and prevent the development of associated diseases. These small-molecule drugs act like molecular ‘chaperones’ for the defective protein, accelerating folding to the correct state.

Cambridge Enterprise helped in Z Factor’s formation in 2015, licensing key intellectual property to the company. ̽��ֱ��company has already identified dozens of molecules that can correct the folding defect caused by the Z mutation, and shown that some of these drug candidates can increase Alpha-1-antitrypsin levels in an in vivo model of AATD.

Z Factor is now working to select the best molecules for use as a drug in human trials. ̽��ֱ��company expects to reach the clinic with its lead candidate in 2019.

“We are delighted to work once again with Cambridge Enterprise to ensure this exciting basic science is rapidly and efficiently translated into new medicines for a surprisingly common and debilitating cause of liver and lung disease,” said David Grainger, Partner at Medicxi and Executive Chairman at Z Factor.

Following closely on the announcement of investments in ApcinteX and SuperX earlier this year, the Z Factor Series A brings the total raised during 2017 by companies founded by Professor Huntington, one of Cambridge’s most successful serial entrepreneurs, to almost £30 million. “Jim is a leading academic innovator and Z Factor is dedicated to developing a therapy that will address a serious unmet medical need,” said Christine Martin from Cambridge Enterprise, and a Director at Z Factor.

A ̽��ֱ�� of Cambridge spin-out company has raised £7 million in new funding, which will help in the development of treatments for liver and lung disease.

Jim Huntington

̽��ֱ��crystal structure of a trimer of Z alpha-1-antitrypsin revealed the C-terminal domain-swap mechanism of polymerisation and the structural defect caused by the E342K mutation.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Potential new treatment for haemophilia developed by Cambridge researchers

cjb250 — Thu, 27 Oct 2016 15:00:19 +0000

Around 400,000 individuals around the world are affected by haemophilia, a genetic disorder that causes uncontrolled bleeding. Haemophilia is the result of a deficiency in proteins required for normal blood clotting – factor VIII for haemophilia A and factor IX for haemophilia B. Currently, the standard treatment is administration of the missing clotting factor. However, this requires regular intravenous injections, is not fully effective, and in about a third of patients results in the development of inhibitory antibodies. Nearly three-quarters of haemophilia sufferers have no access to treatment and have a life-expectancy of only 10 years.

In a study published online today in Blood, the Journal of the American Society of Hematology, researchers report on a novel approach that gives the clotting process more time to produce thrombin, the enzyme that forms blood clots. They suggest this treatment could one day help all patients with haemophilia, including those who develop antibodies against standard therapy. ̽��ֱ��therapy is based on observations relating to a disorder associated with excessive clotting, known as factor V Leiden.

“We know that patients who have haemophilia and also have mutations that increase clotting, such as factor V Leiden, experience less-severe bleeding,” says study co-author Dr Trevor Baglin, Consultant Haematologist at Addenbrooke’s Hospital, Cambridge ̽��ֱ�� Hospitals.

Dr Baglin and colleagues therefore pursued a strategy of reducing the activity of an anticoagulant enzyme, known as activated protein C (APC). ̽��ֱ��principal function of APC is to breakdown the complex that makes thrombin, and the factor V Leiden mutation slows this process. ̽��ֱ��team, led by Professor Jim Huntington, exploited this insight by developing a specific inhibitor of APC based on a particular type of molecule known as a serpin.

“We hypothesized that if we targeted the protein C pathway we could prolong thrombin production and thereby induce clotting in people with clotting defects, such as haemophilia sufferers,” says Professor Huntington, from the Cambridge Institute for Medical Research at the ̽��ֱ�� of Cambridge. “So, we engineered a serpin that could selectively prevent APC from shutting down thrombin production before the formation of a stable clot.”

To test their theory, the team administered the serpin to mice with haemophilia B and clipped their tails. ̽��ֱ��researchers found that the amount of blood loss decreased as the dose increased, with the highest dose reducing bleeding to the level found in normal mice. Further studies confirmed that the serpin helped haemophilia mice form stable clots, with higher doses resulting in faster clot formation. ̽��ֱ��serpin was also able to increase thrombin production and accelerate clot formation when added to blood samples from haemophilia A patients.

“It’s our understanding that because we are targeting a general anti-clotting process, our serpin could effectively treat patients with either haemophilia A or B, including those who develop resistance to more traditional therapy,” adds Professor Huntington. “Additionally, we have focused on engineering the serpin to be long-acting and to be delivered by injection under the skin instead of directly into veins. This will free patients from the inconvenience of having to receive infusions three times a week, as is the case with current treatments.”

̽��ֱ��research team hopes that the discovery can be rapidly developed into an approved medicine to provide improved care to haemophilia sufferers around the world.

“Within three years, we hope to be conducting our first-in-man trials of a subcutaneously-administered form of our serpin,” says Dr Baglin. “It is important to remember that the majority of people in the world with haemophilia have no access to therapy. A stable, easily-administered, long-acting, effective drug could bring treatment to a great deal many more haemophilia sufferers.”

This study forms part of a patent application, filed in the name of Cambridge Enterprise, and the modified serpin is being developed by a start-up company, ApcinteX, with funding from Medicxi.

Adapted from a press release by American Society of Hematology.

Reference
Polderdijk, SGI et al. Design and characterization of an APC-specific serpin for the treatment of haemophilia. Blood; 27 Oct 2016; DOI: 10.1182/blood-2016-05-718635

A new treatment that might one day help all patients with haemophilia, including those that become resistant to existing therapies, has been developed by researchers at the ̽��ֱ�� of Cambridge.

Within three years, we hope to be conducting our first-in-man trials

Trevor Baglin

Ginny

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution-ShareAlike

Six world-changing ideas in 90 seconds

Anonymous — Mon, 09 Nov 2015 10:24:04 +0000

̽��ֱ��film, a distinctive take on innovation, employs a custom-built chain-reaction device, taking viewers beyond the licences, patents and investment that are central to CE, by illustrating the impact of commercialising ̽��ֱ�� research.

“I have a drawer full of promotional videos from other companies that I’ll never watch because they all mirror the same ‘talking head’ format,” said Cambridge Enterprise CEO Tony Raven. “We wanted something that would grab people’s attention and get them telling our story, something outside the box.”

Thus was born CE’s take on the classic ‘Rube Goldberg’ machine, which was named after the American inventor and cartoonist. His illustrations depicted deliberately complex inventions performing simple tasks, usually as a chain reaction.

Using models, pyrotechnics and one very patient ̽��ֱ�� Professor, Cambridge Enterprise’s video illustrates some of the work the company has supported commercially: the anti-thrombin drug ichorcumab, which has the potential to save millions of lives, a revolutionary suspension technology used in Formula 1 racing, a programme to prevent ideological extremism and intergroup conflict, a flower seed mix that is helping the UK’s bee population survive and flourish, software that creates unique music at the touch of a button, and a breakthrough in DNA sequencing technology.

“CE played a crucial role in all steps of the development of ichorcumab – from patenting to licensing to the final negotiation to get this taken over by a big pharma,” said ̽��ֱ�� of Cambridge Professor Jim Huntington, Cambridge Institute for Medical Research, who appears in the opening frames of the film. “They played a critical role throughout and we couldn’t have done it without them.”

It took three weeks to build the machine. And on the day of the shoot, it took a team of 15 from Greenwich-based Contra to capture the continuous, unedited final take. Things went right. Things went wrong (you can watch the ‘making of’ film). Just resetting the machine after every failed take took half an hour (sweeping up flower seeds and sand, and rigging sparklers among other tasks).

“We felt a Rube Goldberg machine would be the perfect approach for Cambridge Enterprise,” said Contra Agency Director David Hayes. “We couldn’t be happier with the end result.”

Originally published on the Cambridge Enterprise website.

Cambridge Enterprise (CE), the commercialisation arm of the ̽��ֱ�� of Cambridge, has launched a film that showcases some of the world-changing ideas it has supported in the journey to market – from a drug with the potential to save millions of lives to a flower seed mix that helps bees.

CE played a crucial role in all steps of the development of ichorcumab – from patenting to licensing to the final negotiation to get this taken over by a big pharma. They played a critical role throughout and we couldn’t have done it without them

Jim Huntington

Cambridge Enterprise - #nextgreatidea

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

How snake bites could help prevent heart attacks

amb206 — Wed, 28 Oct 2015 10:51:31 +0000

Scroll to the end of the article to listen to the podcast.

Recent reports of a world shortage of anti-venom have drawn attention to the dangers of snake bite, especially in rural areas of developing countries where many people work in the fields, often without shoes to protect them.

Although most of the world’s 3,000 or more snake species are not venomous, several hundred species are. Among them is the Australian brown snake (Pseudonaja textilis). Judged to be the world’s second most venomous land snake (the most venomous is the black mamba), it thrives in the populous eastern side of the country. ̽��ֱ��brown snake only attacks humans as a last resort but, if untreated, its bite can prove fatal.

Snakes store venom in glands in their mouths and deliver it into their victims through hollow fangs. For many years, scientists thought that snakes made venom by modifying the proteins present in their spit but not elsewhere in their bodies. This argument made sense because snake spit contains substances that enable them to break down and digest their prey.

Recent research suggests a different picture: the vast majority of the proteins and enzymes found in venoms are very similar to substances found in other parts of snakes’ bodies – such as their livers and digestive organs. ̽��ֱ��genes that control the production of these substances in snakes become activated in the salivary glands where they produce venoms.

“Weaponising is the term we use to describe the way in which snakes like the Australian brown convert a protein utilised for their own biology into a toxin – without poisoning themselves. In some cases snakes hijack their own clotting mechanisms to make venom that, once injected, causes widespread consumption of clotting factors, microthrombosis in organs and systemic bleeding,” says Professor Jim Huntington, a principal investigator at Cambridge Institute for Medical Research (CIMR).

“By understanding more about the weaponised proteins, we can learn more about an essential attribute of blood, its ability to clot when needed – in humans as well as snakes.”

̽��ֱ��focus of Huntington’s lab is the development of a detailed understanding of the regulatory mechanisms that determine haemostatic balance – the balance between bleeding and thrombosis. It is expected that such information will inform the development of therapies for the prevention and treatment of diseases such as haemophilia, deep vein thrombosis, pulmonary embolism, heart attack and stroke – all of which are devastating conditions.

Snake venom offers a route to a better understanding of the haemostatic system. In 2013, Huntington and colleagues published research that revealed the crystal structure of the prothrombinase complex from the venom of the brown snake. This complex is quite similar to human prothrombinase which converts prothrombin to thrombin, the final step in the blood coagulation cascade. An excess production of thrombin causes thrombosis, and insufficient production of thrombin results in bleeding.

̽��ֱ��crystal structure of brown snake venom enabled Huntington’s lab to gain new insights into the architecture and mechanism of the prothrombinase complex. Work is ongoing to determine how the snake’s prothrombinase relates to human prothrombinase and the intrinsic Xase complex (the proteins that activate coagulation factor X). Similar research from the Huntington lab has recently led to the creation of a new drug candidate for the treatment of thrombosis; ‘ichorcumab’ is currently in preclinical development as an antithrombotic agent that does not cause bleeding.

Only in the last 50 years have scientists begun to explore the potentially positive contribution of venoms to medicine. For many hundreds of years, snakes have been numbered among the most dangerous creatures on earth – to be avoided at all costs – and snake venom has long evoked fear and curiosity. Before the development of the first anti-venom at the Pasteur Institute in French Indochina in the 1890s, a bite from a venomous snake could mean death. Even today, the annual global death toll from snake bites is conservatively estimated at 20,000, and could be as high as 94,000.

PhD student James Hall (Department of History and Philosophy of Science) is looking at the serpentine narratives that unfolded during British involvement India from the later 18th century, initially under the rule of the East India Company and then under the Crown Raj from 1858. His research explores the ways in which moral attitudes to snakes informed attempts to describe and categorise them and shaped early attempts to assess the nature and effects of venom on human and other animal bodies.

Hall’s source materials are scientific books and papers, newspapers and periodicals, travelogues, and government archives from Britain and India, as well as the literature of the colonial world. A famous example of the latter is Rudyard Kipling’s short story Rikki-Tikki-Tavi from ̽��ֱ��Jungle Book (1894). It charmingly anthropomorphises the contest between good (in the character of the valiant mongoose Rikki) and evil (the deadly cobras Nag and Nagaina), with the drama taking place in the home of a middle-class British family living in India. Rikki’s bravery saves the innocent boy Teddy from a fatal snake bite.

“Snakes loomed large in the imperial imagination. Kipling’s story is typical of how snakes were typecast as villains in Victorian fiction. ̽��ֱ��cobras embody recurrent fears about the invasion of the supposedly hostile Indian environment into domestic spaces,” says Hall. “Snakes in India actually harmed very few Europeans, but when new statistical data revealed something of the extent of indigenous deaths due to snake bite, the problem became a challenge for a benevolent science as part of the rhetoric of the ‘civilising mission’.”

Humans and other primates are believed to have evolved an instinctive revulsion for snakes. This innate fear is reinforced by key narratives in the Bible, which remained a key authority on animals in the 19th century. In the creation story, the serpent wreaks havoc in the Garden of Eden by craftily tempting Eve to eat an apple from the Tree of Knowledge. Among the hundreds of pictorial representations of this story is German artist Johann König’s painting, Adam and Eve in Paradise (circa 1629), in the Fitzwilliam Museum.

“König’s snake shows some similarity to a European viper or adder. In such scenes the serpent is often seen coiled around the tree, watching on. Earlier depictions sometimes show the serpent in a more humanoid form, with a head, torso and upper limbs.

" ̽��ֱ��original physical form of the serpent in the Garden was a source of debate given that it was only afterwards cursed by God to crawl on its belly,” says Hall.

“ ̽��ֱ��poor biblical reputation of snakes contributed to their unpopularity as objects of scientific study. But there were also practical obstacles to snake science relating to the collection, transportation, and preservation of snakes. Research into the effects of venom involved carrying out technically difficult and controversial experiments.”

From the 1820s, living snakes were collected to exhibit in newly-opened zoos in Britain. They had earlier appeared in travelling menageries. Snake specimens in alcohol, snakeskins and prepared skeletons had been mainstays of natural history collections from much earlier, but the number of species increased dramatically with imperial expansion in the 19th century.

At the Zoological Society’s gardens in Regent’s Park in London, visitors had the opportunity to see venomous snakes face-to-face at the new reptile house, which opened in 1849. Thousands flocked to see the snakes, including men of science such as Charles Darwin, who took the opportunity to carry out research into animal emotions.

̽��ֱ��reptile house was conceived and marketed as an educational resource, but many people visited it for the thrill of seeing (and provoking) dangerous snakes up close, and ended up confirming their own preconceived ideas. Tragedy struck in 1852 when a keeper of reptiles, Edward Gurling, was bitten on the nose by a cobra and killed. ̽��ֱ��Zoological Society moved quickly to reassure the public of the safety of the establishment, and the keeper was described as being drunk from a night of gin drinking and acting with “rashness and indiscretion”.

“ ̽��ֱ��death of Gurling was an important moment for scientific research into venomous snakes,” says Hall. “It led to an upsurge in interest in venomous snakes and renewed efforts to find an antidote to their venom in the colonies. Correspondents wrote to ̽��ֱ��Times offering up their own treatments for snake bite guaranteed by time spent in Africa and on the subcontinent. But it would be another four decades before the first anti-venom was developed.”

Next in the Cambridge Animal Alphabet: W is for an animal that made the journey from a beach in Sussex, to pride of place in the Museum of Zoology.

Have you missed the series so far? Catch up on Medium here.

Inset images: Aboriginal painting of the prothrombinase complex (Tom Murray-Rust); Adam and Eve in Paradise by Johann König (Fitzwilliam Museum); Detail from Adam and Eve in Paradise by Johann König (Fitzwilliam Museum); Illustration of the Zoological Society’s reptile house (Illustrated London News, 2 June 1849).

The Cambridge Animal Alphabet series celebrates Cambridge's connections with animals through literature, art, science and society. Here, V is for Venomous Snake: an animal that has long evoked fear and curiosity, but is revealing important clues for the development of treatments for some devastating conditions.

Weaponising is the term used describe the way in which snakes convert a substance into venom – without poisoning themselves

Jim Huntington

Museum of Zoology, Cambridge

Skull of Bitus arietans – or Puff Adder – from the family Viperidae

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes