探花直播 of Cambridge - nervous system

鈥榃raparound鈥� implants represent new approach to treating spinal cord injuries

sc604 — Wed, 08 May 2024 18:01:25 +0000

A team of engineers, neuroscientists and surgeons from the 探花直播 of Cambridge developed the devices and used them to record the nerve signals going back and forth between the brain and the spinal cord. Unlike current approaches, the Cambridge devices can record 360-degree information, giving a complete picture of spinal cord activity.

Tests in live animal and human cadaver models showed the devices could also stimulate limb movement and bypass complete spinal cord injuries where communication between the brain and spinal cord had been completely interrupted.

Most current approaches to treating spinal injuries involve both piercing the spinal cord with electrodes and placing implants in the brain, which are both high-risk surgeries. 探花直播Cambridge-developed devices could lead to treatments for spinal injuries without the need for brain surgery, which would be far safer for patients.

While such treatments are still at least several years away, the researchers say the devices could be useful in the near-term for monitoring spinal cord activity during surgery. Better understanding of the spinal cord, which is difficult to study, could lead to improved treatments for a range of conditions, including chronic pain, inflammation and hypertension. 探花直播results are reported in the journal Science Advances.

鈥� 探花直播spinal cord is like a highway, carrying information in the form of nerve impulses to and from the brain,鈥� said Professor George Malliaras from the Department of Engineering, who co-led the research. 鈥淒amage to the spinal cord causes that traffic to be interrupted, resulting in profound disability, including irreversible loss of sensory and motor functions.鈥�

探花直播ability to monitor signals going to and from the spinal cord could dramatically aid in the development of treatments for spinal injuries, and could also be useful in the nearer term for better monitoring of the spinal cord during surgery.

鈥淢ost technologies for monitoring or stimulating the spinal cord only interact with motor neurons along the back, or dorsal, part of the spinal cord,鈥� said Dr Damiano Barone from the Department of Clinical Neurosciences, who co-led the research. 鈥淭hese approaches can only reach between 20 and 30 percent of the spine, so you鈥檙e getting an incomplete picture.鈥�

By taking their inspiration from microelectronics, the researchers developed a way to gain information from the whole spine, by wrapping very thin, high-resolution implants around the spinal cord鈥檚 circumference. This is the first time that safe 360-degree recording of the spinal cord has been possible 鈥� earlier approaches for 360-degree monitoring use electrodes that pierce the spine, which can cause spinal injury.

探花直播Cambridge-developed biocompatible devices 鈥� just a few millionths of a metre thick 鈥� are made using advanced photolithography and thin film deposition techniques, and require minimal power to function.

探花直播devices intercept the signals travelling on the axons, or nerve fibres, of the spinal cord, allowing the signals to be recorded. 探花直播thinness of the devices means they can record the signals without causing any damage to the nerves, since they do not penetrate the spinal cord itself.

鈥淚t was a difficult process, because we haven鈥檛 made spinal implants in this way before, and it wasn鈥檛 clear that we could safely and successfully place them around the spine,鈥� said Malliaras. 鈥淏ut because of recent advances in both engineering and neurosurgery, the planets have aligned and we鈥檝e made major progress in this important area.鈥�

探花直播devices were implanted using an adaptation to routine surgical procedure so they could be slid under the spinal cord without damaging it. In tests using rat models, the researchers successfully used the devices to stimulate limb movement. 探花直播devices showed very low latency 鈥� that is, their reaction time was close to human reflexive movement. Further tests in human cadaver models showed that the devices can be successfully placed in humans.

探花直播researchers say their approach could change how spinal injuries are treated in future. Current attempts to treat spinal injuries involve both brain and spinal implants, but the Cambridge researchers say the brain implants may not be necessary.

鈥淚f someone has a spinal injury, their brain is fine, but it鈥檚 the connection that鈥檚 been interrupted,鈥� said Barone. 鈥淎s a surgeon, you want to go where the problem is, so adding brain surgery on top of spinal surgery just increases the risk to the patient. We can collect all the information we need from the spinal cord in a far less invasive way, so this would be a much safer approach for treating spinal injuries.鈥�

While a treatment for spinal injuries is still years away, in the nearer term, the devices could be useful for researchers and surgeons to learn more about this vital, but understudied, part of human anatomy in a non-invasive way. 探花直播Cambridge researchers are currently planning to use the devices to monitor nerve activity in the spinal cord during surgery.

鈥淚t鈥檚 been almost impossible to study the whole of the spinal cord directly in a human, because it鈥檚 so delicate and complex,鈥� said Barone. 鈥淢onitoring during surgery will help us to understand the spinal cord better without damaging it, which in turn will help us develop better therapies for conditions like chronic pain, hypertension or inflammation. This approach shows enormous potential for helping patients.鈥�

探花直播research was supported in part by the Royal College of Surgeons, the Academy of Medical Sciences, Health Education England, the National Institute for Health Research, MRC Confidence in Concept, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).

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Reference:
Ben J Woodington, Jiang Lei et al. 鈥�Flexible Circumferential Bioelectronics to Enable 360-degree Recording and Stimulation of the Spinal Cord.鈥� Science Advances (2024). DOI: 10.1126/sciadv.adl1230

A tiny, flexible electronic device that wraps around the spinal cord could represent a new approach to the treatment of spinal injuries, which can cause profound disability and paralysis.

Because of recent advances in both engineering and neurosurgery, the planets have aligned and we鈥檝e made major progress in this important area

George Malliaras

SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY

Illustration of spinal cord

探花直播text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright 漏探花直播 of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways 鈥� on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Robotic nerve 鈥榗uffs鈥� could help treat a range of neurological conditions

sc604 — Fri, 26 Apr 2024 08:55:34 +0000

探花直播researchers, from the 探花直播 of Cambridge, combined flexible electronics and soft robotics techniques to develop the devices, which could be used for the diagnosis and treatment of a range of disorders, including epilepsy and chronic pain, or the control of prosthetic limbs.

Current tools for interfacing with the peripheral nerves 鈥� the 43 pairs of motor and sensory nerves that connect the brain and the spinal cord 鈥� are outdated, bulky and carry a high risk of nerve injury. However, the robotic nerve 鈥榗uffs鈥� developed by the Cambridge team are sensitive enough to grasp or wrap around delicate nerve fibres without causing any damage.

Tests of the nerve cuffs in rats showed that the devices only require tiny voltages to change shape in a controlled way, forming a self-closing loop around nerves without the need for surgical sutures or glues.

探花直播researchers say the combination of soft electrical actuators with neurotechnology could be an answer to minimally invasive monitoring and treatment for a range of neurological conditions. 探花直播results are reported in the journal Nature Materials.

Electric nerve implants can be used to either stimulate or block signals in target nerves. For example, they might help relieve pain by blocking pain signals, or they could be used to restore movement in paralysed limbs by sending electrical signals to the nerves. Nerve monitoring is also standard surgical procedure when operating in areas of the body containing a high concentration of nerve fibres, such as anywhere near the spinal cord.

These implants allow direct access to nerve fibres, but they come with certain risks. 鈥淣erve implants come with a high risk of nerve injury,鈥� said Professor George Malliaras from Cambridge鈥檚 Department of Engineering, who led the research. 鈥淣erves are small and highly delicate, so anytime you put something large, like an electrode, in contact with them, it represents a danger to the nerves.鈥�

鈥淣erve cuffs that wrap around nerves are the least invasive implants currently available, but despite this they are still too bulky, stiff and difficult to implant, requiring significant handling and potential trauma to the nerve,鈥� said co-author Dr Damiano Barone from Cambridge鈥檚 Department of Clinical Neurosciences.

探花直播researchers designed a new type of nerve cuff made from conducting polymers, normally used in soft robotics. 探花直播ultra-thin cuffs are engineered in two separate layers. Applying tiny amounts of electricity 鈥� just a few hundred millivolts 鈥� causes the devices to swell or shrink.

探花直播cuffs are small enough that they could be rolled up into a needle and injected near the target nerve. When activated electrically, the cuffs will change their shape to wrap around the nerve, allowing nerve activity to be monitored or altered.

鈥淭o ensure the safe use of these devices inside the body, we have managed to reduce the voltage required for actuation to very low values,鈥� said Dr Chaoqun Dong, the paper鈥檚 first author. 鈥淲hat's even more significant is that these cuffs can change shape in both directions and be reprogrammed. This means surgeons can adjust how tightly the device fits around a nerve until they get the best results for recording and stimulating the nerve.鈥�

Tests in rats showed that the cuffs could be successfully placed without surgery, and formed a self-closing loop around the target nerve. 探花直播researchers are planning further testing of the devices in animal models, and are hoping to begin testing in humans within the next few years.

鈥淯sing this approach, we can reach nerves that are difficult to reach through open surgery, such as the nerves that control, pain, vision or hearing, but without the need to implant anything inside the brain,鈥� said Barone. 鈥� 探花直播ability to place these cuffs so they wrap around the nerves makes this a much easier procedure for surgeons, and it鈥檚 less risky for patients.鈥�

鈥� 探花直播ability to make an implant that can change shape through electrical activation opens up a range of future possibilities for highly targeted treatments,鈥� said Malliaras. 鈥淚n future, we might be able to have implants that can move through the body, or even into the brain 鈥� it makes you dream how we could use technology to benefit patients in future.鈥�

探花直播research was supported in part by the Swiss National Science Foundation, the Cambridge Trust, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).

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Reference:
Chaoqun Dong et al. 鈥�Electrochemically actuated microelectrodes for minimally invasive peripheral nerve interfaces.鈥� Nature Materials (2024). DOI: 10.1038/s41563-024-01886-0

Researchers have developed tiny, flexible devices that can wrap around individual nerve fibres without damaging them.

探花直播ability to make an implant that can change shape through electrical activation opens up a range of future possibilities for highly targeted treatments

George Malliaras

XH4D via iStock / Getty Images Plus

Illustration of the human nervous system

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520 million-year-old fossilised nervous system is most detailed example yet found

sc604 — Mon, 29 Feb 2016 20:00:00 +0000

Researchers have found one of the oldest and most detailed fossils of the central nervous system yet identified, from a crustacean-like animal that lived more than 500 million years ago. 探花直播fossil, from southern China, has been so well preserved that individual nerves are visible, the first time this level of detail has been observed in a fossil of this age.

探花直播findings, published in the Proceedings of the National Academy of Sciences, are helping researchers understand how the nervous system of arthropods - creepy crawlies with jointed legs - evolved. Finding any fossilised soft tissue is rare, but this particular find, by researchers in the UK, China and Germany, represents the most detailed example of a preserved nervous system yet discovered.

探花直播animal, called Chengjiangocaris kunmingensis, lived during the Cambrian 鈥榚xplosion鈥�, a period of rapid evolutionary development about half a billion years ago when most major animal groups first appear in the fossil record. C. kunmingensis belongs to a group of animals called fuxianhuiids, and was an early ancestor of modern arthropods 鈥� the diverse group that includes insects, spiders and crustaceans.

鈥淭his is a unique glimpse into what the ancestral nervous system looked like,鈥� said study co-author Dr Javier Ortega-Hern谩ndez, of the 探花直播 of Cambridge鈥檚 Department of Zoology. 鈥淚t鈥檚 the most complete example of a central nervous system from the Cambrian period.鈥�

Over the past five years, researchers have identified partially-fossilised nervous systems in several different species from the period, but these have mostly been fossilised brains. And in most of those specimens, the fossils only preserved details of the profile of the brain, meaning the amount of information available has been limited.

C. kunmingensis looked like a sort of crustacean, with a broad, almost heart-shaped head shield, and a long body with pairs of legs of varying sizes. Through careful preparation of the fossils, which involved chipping away the surrounding rock with a fine needle, the researchers were able to view not only the hard parts of the body, but fossilised soft tissue as well.

探花直播vast majority of fossils we have are mostly bone and other hard body parts such as teeth or exoskeletons. Since the nervous system and soft tissues are essentially made of fatty-like substances, finding them preserved as fossils is extremely rare. 探花直播researchers behind this study first identified a fossilised central nervous system in 2013, but the new material has allowed them to investigate the significance of these finding in much greater depth.

Click to enlarge

探花直播central nervous system coordinates all neural and motor functions. In vertebrates, it consists of the brain and spinal cord, but in arthropods it consists of a condensed brain and a chain-like series of interconnected masses of nervous tissue called ganglia that resemble a string of beads.

Like modern arthropods, C. kunmingensis had a nerve cord 鈥� which is analogous to a spinal cord in vertebrates 鈥� running throughout its body, with each one of the bead-like ganglia controlling a single pair of walking legs.

Closer examination of the exceptionally preserved ganglia revealed dozens of spindly fibres, each measuring about five thousandths of a millimetre in length. 鈥淭hese delicate fibres displayed a highly regular distribution pattern, and so we wanted to figure out if they were made of the same material as the ganglia that form the nerve cord,鈥� said Ortega-Hern谩ndez. 鈥淯sing fluorescence microscopy, we confirmed that the fibres were in fact individual nerves, fossilised as carbon films, offering an unprecedented level of detail. These fossils greatly improve our understanding of how the nervous system evolved.鈥�

For Ortega-Hern谩ndez and his colleagues, a key question is what this discovery tells us about the evolution of early animals, since the nervous system contains so much information. Further analysis revealed that some aspects of the nervous system in C. kunmingensis appear to be structured similar to that of modern priapulids (penis worms) and onychophorans (velvet worms), with regularly-spaced nerves coming out from the ventral nerve cord.

In contrast, these dozens of nerves have been lost independently in the tardigrades (water bears) and modern arthropods, suggesting that simplification played an important role in the evolution of the nervous system.

Possibly one of the most striking implications of the study is that the exceptionally preserved nerve cord of C. kunmingensis represents a unique structure that is otherwise unknown in living organisms. 探花直播specimen demonstrates the unique contribution of the fossil record towards understanding the early evolution of animals during the Cambrian period. 鈥� 探花直播more of these fossils we find, the more we will be able to understand how the nervous system 鈥� and how early animals 鈥� evolved,鈥� said Ortega-Hern谩ndez.聽

探花直播research was supported in part by Emmanuel College, Cambridge.聽

Reference:
Jie Yang et. al. 鈥� 探花直播fuxianhuiid ventral nerve cord and early nervous system evolution in Panarthropoda.鈥� PNAS (2016). DOI: 10.1073/pnas.1522434113

A 520 million-year-old fossilised nervous system 鈥� so well-preserved that individually fossilised nerves are visible 鈥� is the most complete and best example yet found, and could help unravel how the nervous system evolved in early animals.

探花直播more of these fossils we find, the more we will be able to understand how the nervous system 鈥� and how early animals 鈥� evolved.

Javier Ortega-Hern谩ndez

Top: Jie Yang, Bottom: Yu Liu

Top: Complete specimen of Chengjiangocaris kunmingensis from the early Cambrian Xiaoshiba biota of South China. Bottom: Magnification of ventral nerve cord of Chengjiangocaris kunmingensis.

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

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Opinion: Our 500 million-year-old nervous system fossil shines a light on animal evolution

Anonymous — Mon, 29 Feb 2016 16:50:59 +0000

探花直播nervous system is the command centre of an animal鈥檚 body, carrying all the complex electrical signals for the actions that keep it alive, such as moving and eating. Because of its critical function, the nervous system also contains a lot of information about an animal鈥檚 evolution, and can even help us understand how different groups relate to each other. But preserved fossilised nervous systems from extinct creatures are extremely rare.

That鈥檚 why my colleagues and I were excited to discover one of the most detailed and well-preserved nervous system fossils ever found, from a crustacean-like animal known as a fuxianhuiid that lived more than 500m years ago. These fossils 鈥� which come from the Xiaoshiba biota in south China 鈥� are so well preserved that you can see individual nerve roots ten times thinner than a human hair. 探花直播findings offer the most detailed view of the nervous system in early animals available to date, and inform us about the early evolution of the nervous system in these creatures and their close relatives.

Ancient arthropod

探花直播fuxianhuiids (pronounced foo-see-an-who-eeds) were primitive animals known only to have lived during the early Cambrian period in China, some 515-520m years ago. Fuxianhuiids are widely regarded as being important for understanding the early evolution of the arthropods. This is a large group of animals with jointed limbs and hard exoskeletons that also includes insects, arachnids and crustaceans. So finding preserved nervous tissues in fuxianhuiids tells us a lot about their early evolution and that of their close relatives.

By painstakingly chipping away small pieces of rock from the fossil using a fine needle, my colleagues in China were able to reveal the ventral nerve cord running through their entire body. 探花直播ventral nerve cord is part of the nervous system, very much similar to our spinal cord, and it resembles a string of beads.

Each of the 鈥渂eads鈥� actually corresponds to a ganglion, a condensed mass of nerve cells whose function is to control the legs on each segment of the body in fuxianhuiids and other arthropods. Our fossils also preserve dozens of delicate nerves that emerge at either side of the ventral nerve cord and that would have been connected to the legs and other parts of the body.

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Ventral cord. Jie Yang (Yunnan 探花直播, China) (left) and Javier Ortega-Hern谩ndez ( 探花直播 of Cambridge, UK)

聽

Finding the fossilised remains of an animal鈥檚 nervous system is extremely unusual, as the brain and ventral nerve cord are mainly made of fatty tissues and decay very quickly under normal circumstances. But under exceptional conditions 鈥� such as very rapid burial in environments with little oxygen 鈥� these delicate structures can be preserved in the fossil record.

In the last five years, various studies, have reported the preservation of brains in Cambrian arthropods, which has greatly improved our understanding of their evolution. But in most cases, we can only recognise the broad outline of the brain and so there are limits to the information that can be extracted from the fossils. Our study is the first time that a complete ventral nerve cord has been described in such an extraordinary level of detail.

More importantly, the ventral nerve cord of fuxianhuiids is rather unique among arthropods. Whereas most arthropods also posses condensed ganglia, they generally lack the dozens of delicate nerve roots that are found in fuxianhuiids. However, this peculiar organisation can be found in velvet worms (or onychophorans), a group of animals resembling worms with legs that are cousins to the arthropods. So the fuxianhuiid ventral nerve cord is an intermediate between the nervous system of arthropods and velvet worms.

Common ancestral link

This means we can interpret the dozens of nerves in fuxianhuiids as an ancient trait inherited from the last common ancestor between velvet worms and arthropods. This is similar to how the the feet of modern birds resemble the feet of dinosaurs, because they were also inherited from their last common ancestor

By contrast, the presence of ganglia on the nerve cord of fuxianhuiids is an innovation that occurred in the evolution of arthropods. Keeping with the analogy, this is like how feathers are an innovation that occurred in the evolution of birds.

探花直播most interesting conclusion we can draw is that the origin of the arthropod nervous system required the dramatic reduction in the number of nerves, and that this event took place after the early Cambrian period. Without fuxianhuiids, it would have been impossible to attain this depth of knowledge on the evolution of the nervous system.

Javier Ortega-Hernandez, Research fellow in palaeobiology, 探花直播 of Cambridge

This article was originally published on 探花直播Conversation. Read the original article.

探花直播opinions expressed in this article are those of the individual author(s) and do not represent the views of the 探花直播 of Cambridge.

Javier Ortega-Hern谩ndez (Department of Zoology) discusses what the discovery of the earliest known fossilised nervous system could tell us about evolution.

Top: Jie Yang, Bottom: Yu Liu

Top: Complete specimen of Chengjiangocaris kunmingensis from the early Cambrian Xiaoshiba biota of South China. Bottom: Magnification of ventral nerve cord of Chengjiangocaris kunmingensis.

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

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Royal Society announces new Fellows

bjb42 — Fri, 21 May 2010 00:00:00 +0000

探花直播new Fellows join the ranks of the UK and Commonwealth's leading scientists as the Society celebrates its 350th Anniversary.

Lord Rees, President of the Royal Society said: "These scientists follow in the footsteps of early Fellows such as Isaac Newton, Robert Boyle and Robert Hooke. 探花直播new Fellows announced today embody the spirit of enquiry, dedicated to 'the relief of man's estate' on which the Royal Society was founded. That spirit is as alive today as it was 350 years ago."

探花直播new Fellows are:

Professor Andrea Brand, Herchel Smith Professor of Molecular Biology at the Gurdon Institute and the Department of Physiology, Development and Neuroscience and a Fellow of Jesus College, is distinguished for her pioneering work on the development of the nervous system. Using Drosophila as a model organism, and using sophisticated live imaging techniques, she has explained how cell fate determinants become localised to one side of a cell, allowing neural precursors to divide asymmetrically in a stem cell-like fashion.

Professor Nicola Clayton, Professor of Comparative Cognition in the Department of Experimental Psychology and Clare College Graduate Tutor, has pioneered new procedures for the experimental study of memory, planning and social cognition in animals, all attributes that have been claimed to be uniquely human, and her work has changed our view of animal intelligence and its relationship to human memory and cognition.

Professor Ben Green, Herchel Smith Professor of Pure Mathematics and a Fellow of Trinity College, has proved a number of remarkable results in arithmetic combinatorics, the highlight of which is his proof, with Terence Tao, that the prime numbers contain arithmetic progressions of all lengths.

Professor Roger Hardie, Professor of Cellular Neuroscience in the Department of Physiology, Development and Neuroscience, is distinguished for his extensive studies on invertebrate visual transduction which have transformed our wider understanding of cell signalling. His demonstration that the Drosophila trp and trpl genes code for selective calcium channels was the seminal observation that launched the TRP channel field, now a major part of calcium signalling and a focus of medical research.

Dr Michael Hastings, MRC Staff Scientist at the MRC Laboratory of Molecular Biology, is distinguished for his highly influential contributions to our understanding of biological clocks through the study of the suprachiasmatic nucleus (SCN) of the hypothalamus. He was instrumental in taking circadian neurobiology to the molecular and cell biological level.

Professor Max Pettini, Professor of Observational Astronomy at the Institute of Astronomy, is distinguished for his extensive observational achievements and insightful interpretations of the chemical and physical conditions of interstellar matter seen in a wide range of cosmic environments. His early research led to the discovery that our Galaxy is surrounded by a halo of hot ionised gas, verifying a prediction made decades earlier.

Professor Wolf Reik, Honorary Professor of Epigenetics in the Department of Physiology, Development and Neuroscience, is distinguished for his fundamental discoveries of epigenetic mechanisms in mammalian development, physiology, genome reprogramming, and human diseases. His work led to the discovery of the molecular mechanism of genomic imprinting, and uncovered non-coding RNA and chromatin looping regulating imprinted genes, which he showed to be involved in foetal nutrition, growth, and disease.

Seven Cambridge researchers are among the 44 new Fellows announced by the Royal Society this week.

These scientists follow in the footsteps of early Fellows such as Isaac Newton, Robert Boyle and Robert Hooke.

Lord Rees, President of the Royal Society

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RSC busts

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Campath: from innovation to impact

bjb42 — Sat, 01 Aug 2009 00:00:00 +0000

探花直播journey taken by Campath-1H from the laboratory to its imminent use as a new treatment for multiple sclerosis (MS) is deeply rooted in fundamental research and illustrates the role that academic research plays throughout the development of new innovations. In the late 1970s, Professor Herman Waldmann, then a lecturer in the Department of Pathology at the 探花直播 of Cambridge and now Head of the Sir William Dunn School of Pathology, Oxford, was applying for his first Medical Research Council programme grant. 鈥業 was interested in understanding immunological tolerance [see Glossary below],鈥� remembers Waldmann, a process that was poorly understood at that time, as were many other aspects of the human immune system.

探花直播immune system is a network of many cell types that protect the body from bacteria and other disease-causing organisms (pathogens). When a pathogen enters the body and infects human cells, immune system cells that circulate in the blood called T and B lymphocytes detect its presence by binding to pathogen-specific molecules called antigens and become activated. 探花直播activated T lymphocytes kill the pathogen-infected cells directly or help the activated B lymphocytes make antibodies, secreted proteins that recognise specific antigens. These antibodies coat the pathogens, which labels them for destruction by other immune system cells through processes that immunologists call effector mechanisms.

Although a person鈥檚 immune system responds quickly to pathogens, it usually ignores self antigens, molecules that are present in the person鈥檚 own body. This lack of response is called tolerance. In 1978, says Waldmann, 鈥榩eople thought that to make a good immune response, lymphocytes had to cooperate with each other and that if there wasn鈥檛 good cooperation between lymphocytes, the default state was tolerance.鈥�

One way to investigate tolerance, therefore, might be to reduce the number of lymphocytes in an experimental animal and then expose the animal to a new antigen. If this theory about tolerance was right, the animal should become tolerant to the antigen. But how could the number of lymphocytes in an animal be reduced?

探花直播approach Waldmann took was to make an anti-lymphocyte antibody using a technique that had recently been developed by Dr C茅sar Milstein at the nearby Laboratory of Molecular Biology. By fusing myeloma cells (cancer cells that develop from B lymphocytes) with cells from the spleen, Milstein had managed to make cell lines that indefinitely produced large amounts of a single antibody. Such monoclonal antibodies were ideal for Waldmann鈥檚 experiment.

鈥� 探花直播immediate medical applications of this experiment were very clear,鈥� says Waldmann. 鈥業f it worked, it would provide a way to improve bone marrow transplants.鈥� These transplants are used to 鈥榬escue鈥� cancer patients whose blood system has been destroyed by radiotherapy. Donated bone marrow rescues these patients because it contains stem cells, precursor cells that can provide the recipient with a new blood system. Unfortunately, donated bone marrow also contains mature lymphocytes, which can attack the patient. Waldmann reasoned that, by using a monoclonal antibody to remove mature lymphocytes from the donor marrow, this potentially fatal 鈥榞raft-versus-host disease鈥� could be avoided. Importantly, however, Waldmann also saw his work as a way to investigate basic immunological mechanisms.

Campath antibodies and bone marrow transplants

Late in 1979, Waldmann and his team immunised a rat with human lymphocytes and fused its spleen cells with a rat myeloma cell line. Over Christmas, Waldmann isolated several antibody-producing cell lines from this Campath-1 fusion (鈥楥ampath鈥� stands for Cambridge Pathology) and his team set to work to identify an antibody that could kill mature T lymphocytes without damaging the bone marrow stem cells. In particular, the researchers looked for an antibody that could activate complement, one of the immune system鈥檚 effector mechanisms. 探花直播monoclonal antibody that best met these criteria was an 鈥業gM鈥� antibody. B lymphocytes can make several different types of antibody (isotypes), each of which behaves differently in terms of which immune effector mechanisms it interacts with to destroy pathogens. This particular IgM (Campath-1M) activated complement efficiently and almost completely eliminated T lymphocytes in test tubes.

探花直播first bone marrow transplants that used Campath-1M for T-lymphocyte depletion were performed in the early 1980s. Bone marrow taken from donors was treated with Campath-1M in test tubes and the T-lymphocyte-depleted bone marrow was then injected into the graft recipients. This procedure successfully reduced the incidence of graft-versus-host disease but a new problem soon became evident. Some of the bone marrow recipients rejected the transplant. Their immune system had recognised the marrow as foreign even though the patients had been given drugs before the transplant to suppress their immune responses. Clearly, a better method was needed to suppress the patient鈥檚 immune response.

An obvious way to do this was to treat both the donor bone marrow and the transplant recipient with a T-lymphocyte-depleting antibody but the researchers knew that Campath-1M worked poorly in patients so they returned to the laboratory to find another antibody isotype that would be more effective. Their results suggested that an IgG2b antibody was likely to work best. Unfortunately, none of the antibodies produced in the Campath-1 fusion had this isotype. However, monoclonal-antibody-producing cell lines sometimes spontaneously start to make antibodies of a different isotype. So, the researchers painstakingly screened a cell line that was making an IgG2a antibody until they found a cell that had switched to making an IgG2b antibody 鈥� Campath-1G. Like the original Campath-1M (and Campath-1H; see below), Campath-1G binds to a molecule called CD52 that is present on lymphocytes and some other human cells.

Campath-1G and Campath-1H go into patients

鈥極nce we knew we had an antibody that worked in patients, we started to talk to a variety of clinicians who might be interested in using an anti-lymphocyte antibody,鈥� explains Waldmann. Some of these clinicians were treating patients who had lymphocytic leukaemia, a blood cancer in which lymphocytes replicate uncontrollably. Two patients with this type of cancer were duly treated with Campath-1G and initially responded well although both patients subsequently relapsed. In one patient, their immune system had recognised Campath-1G 鈥� a rat antibody 鈥� as foreign and destroyed it.

Clearly, a more-nearly human antibody was needed that would be ignored by the human immune system. Fortuitously, another Cambridge scientist, Professor Sir Greg Winter, had just developed a way to 鈥榟umanise鈥� antibodies. Humanisation is the replacement of some regions in an animal antibody by the equivalent human regions; the animal regions that determine which antigen the antibody recognises are retained in humanised antibodies. Dr Mike Clark, who had joined Waldmann鈥檚 laboratory in 1981, started to make a set of fully and partly humanised antibodies from Campath-1G and, together with other team members, tried to determine which human isotypes would work in patients. Campath-1H, a humanised IgG1, was the result of all this basic research although, says Clark, who is now a Reader in Therapeutic Immunology in the Department of Pathology, 探花直播 of Cambridge, 鈥榯hese days, we think that a partly humanised antibody that retained some more of the rat regions would probably have worked just as well.鈥�

Campath-1H was very successful for the treatment of lymphocytic leukaemia and of non-Hodgkin lymphoma (another type of blood cancer), and for use in bone marrow and solid organ transplants. Clinicians also started to use it to treat several autoimmune diseases including vasculitis (inflammation of the blood vessels), rheumatoid arthritis and MS. 探花直播clinical-grade material needed for these studies was produced in the Therapeutic Antibody Centre (TAC) that Waldmann set up in Cambridge in 1990 with Professor Geoff Hale, a biochemist who had joined Waldmann鈥檚 group at the beginning of the Campath-1H story and who is now Visiting Professor of Therapeutic Immunology at the Sir William Dunn School of Pathology, Oxford. 探花直播TAC moved to Oxford in 1995. 鈥榃ithout Geoff鈥檚 critical contribution and the support of both Cambridge and Oxford 探花直播,鈥� says Waldmann, 鈥榳e would not have been able to initiate many of these studies, including our long-standing collaboration with Alastair Compston in MS.鈥�

Pharmaceutical company involvement

探花直播development of a drug for clinical use is a highly regulated, long and expensive process, so drugs only get to market if pharmaceutical companies become involved in their development. In the early 1980s, the Cambridge researchers assigned the rights for the Campath-1 cell lines to BTG, originally a government body set up to facilitate the exploitation of inventions from UK academics but now an international specialty pharmaceuticals company. In 1985, BTG licensed Campath-1M to Wellcome Biotech, a subsidiary of the Wellcome Foundation. 鈥楳any people were very sceptical in the mid-1980s about the commercial future of antibodies and other biotech drugs but Wellcome was excited by the potential of this new area,鈥� comments Dr Richard Jennings (Director of Technology Transfer and Consultancy Services, Cambridge Enterprise Ltd).

When the basic research being undertaken by Waldmann鈥檚 team suggested that Campath-1G and Campath-1H were more likely to have a clinical future than Campath-1M, these antibodies were also licensed to Wellcome Biotech. Indeed, once Campath-1H had been handed over, the company abandoned its work on the earlier antibodies and started a programme of clinical trials of Campath-1H in rheumatoid arthritis, leukaemia and lymphoma. Meanwhile, the academic scientists continued with their basic research, refining and extending their understanding of how Campath-1H was working in various diseases by collaborating closely with the physicians who were giving the antibody to patients. This research was helped along by the development of new molecular techniques and by improved understanding of the human immune system.

Then, in 1995, Wellcome (which merged with Glaxo that year to become Glaxo-Wellcome) decided to abandon its development of Campath-1H, fearing that Campath-1H would not have a billion-dollar market after all. Although the antibody worked well in some types of leukaemia, it did not work in all leukaemias and, in the rheumatoid arthritis trials, Campath-1H had permanently suppressed patients鈥� immune systems. This decision was very disappointing for Waldmann and his colleagues, who strongly believed in the clinical potential of Campath-1H. 鈥榃e looked at things from a different point of view,鈥� says Waldmann. 鈥楢s academic scientists, when Campath-1H caused unexpected side effects or did not work as well as expected, our response was to look at the evidence, figure out what had gone wrong, and find ways to put it right rather than giving up.鈥�

In 1997, after protracted negotiations with BTG and Glaxo-Wellcome, LeukoSite Inc. took on the licence to develop Campath-1H. LeukoSite, which merged with Millennium Pharmaceuticals in 1999, partnered with ILEX Oncology to complete the development and obtain US approval in 2001 for Campath-1H to be used for the treatment of B-cell chronic lymphocytic leukaemia (CLL) in patients who had failed to respond to conventional chemotherapy. 探花直播licence for Campath-1H was then transferred to ILEX Oncology before, finally, in 2004, Genzyme Corporation acquired ILEX Oncology and the production rights to Campath-1H.

Says Mark Enyedy, Senior Vice- President at Genzyme, 鈥楥ampath-1H has had a particularly tortuous commercial history. I think the many changes of commercial support for this product have impeded the realisation of this drug鈥檚 commercial potential even though products like this always take an enormous time to develop.鈥�

MS 鈥� Campath-1H鈥檚 new market?

Last year, the revenue from the use of Campath-1H for the treatment of CLL was around US$100 million but this income may eventually be dwarfed by the revenue generated from the treatment of early relapsing鈥搑emitting MS with Campath-1H聽(the generic name for the drug is alemtuzumab; its registered name is Campath庐). As in other diseases, the development of Campath-1H for the treatment of MS has relied on academic researchers willing to do the basic research needed to understand how Campath-1H is working in patients and how to make it more effective.

MS is an inflammatory neurological disease that is caused by damage to myelin, a substance that forms an insulating sheath around the nerve fibres in the central nervous system (CNS; the brain and spinal cord). Electrical messages pass along these nerve fibres to control conscious and unconscious actions. If the myelin sheath is damaged these messages can no longer pass smoothly and quickly between the brain and the body.

Most people with MS are initially diagnosed with relapsing鈥搑emitting MS. In this form of the disease, symptoms (which include muscle spasms and stiffness, tremors, bladder and bowel control problems, and pain) occur in episodes that are followed by periods of spontaneous recovery (remissions). Relapses can occur at any time, last for days, weeks or months, and vary in their severity. Most people who have relapsing鈥搑emitting MS eventually develop secondary progressive MS in which the occurrence of relapses wanes but overall disability slowly increases.

Early attempts to treat MS

By the late 1980s, it was becoming clear that MS is an autoimmune disease (a disease in which a person鈥檚 immune system attacks the person鈥檚 own tissues) in which activated T lymphocytes move into the CNS and damage myelin. As Professor Alastair Compston (Professor of Neurology and Head of the Department of Clinical Neurosciences at the 探花直播 of Cambridge) explains, 鈥榳e began to wonder whether we could help patients with MS by preventing the movement of activated lymphocytes from the bloodstream into the brain.鈥� Treatment with Campath-1H looked like one way that this could be achieved and, in 1991, Compston started an 18-year-long collaboration with Waldmann and his team by trying this approach for the first time in a woman who had developed MS some years earlier. 鈥楢t that time, there were no licensed treatments for MS,鈥� says Compston, 鈥榓nd this individual seemed to be facing a particularly grim future. Alarmingly, she actually got much worse for a day or two after receiving Campath-1H but then picked up and remained very well for some years. She even seemed to get back some of her lost functions.鈥�

Keeping in close contact with Waldmann鈥檚 team, Compston and colleagues carefully followed the progress of their patient for about 18 months before treating another six people. 鈥楤y 1994, we had satisfied ourselves that Campath-1H treatment could stop the development of new inflammatory lesions in the brain,鈥� says Compston. In addition, 鈥榠t seemed as though our patients had fewer new attacks after the treatment.鈥�

By 1999, Compston and a clinical trainee, Dr Alasdair Coles, had treated 27 patients, all of whom had already entered the secondary progressive stage of MS. 鈥榃e paused then to analyse our results,鈥� says Compston. &lsq

uo;We realised that, although we had stopped disease activity in terms of new inflammatory brain lesions and had reduced the number of attacks that people were having, most of our patients were continuing to deteriorate.鈥� 探花直播problems that the patients had had when they started Campath-1H treatment were slowly progressing. This observation puzzled the researchers. If MS is an inflammatory autoimmune disease, why was Campath-1H treatment failing to help people in the progressive phase of the disease even though the treatment seemed to turn off inflammation?

探花直播answer to this conundrum, the researchers realised, is that there are two separate processes going on in MS 鈥� inflammation and degeneration. Inflammation causes the attacks in relapsing鈥搑emitting MS but also triggers nerve degeneration. Eventually, the degenerative component of the disease gains a momentum of its own and continues even in the absence of inflammation, which results in slow progression and the accumulation of disabilities that don鈥檛 get better. 鈥楿ntil we used Campath-1H in patients, this separation between inflammation and degeneration was not appreciated,鈥� says Compston, 鈥榖ut its implications were obvious. If this drug was going to be of any use to people with MS, we would have to use it much earlier in the disease process than we had so far.鈥�

Campath-1H for the treatment of relapsing鈥搑emitting MS

Compston and Coles now began to treat some of their patients with relapsing鈥搑emitting MS with Campath-1H. As before, the treatment almost completely stopped new attacks occurring but, in addition, many of these patients actually began to get better. Their various disabilities began to improve. It was time to take Campath-1H into formal clinical trials to prove the drug鈥檚 efficacy and to prepare the way for marketing the drug for the treatment of MS.

With the support of ILEX Oncology (and, from 2004, of Genzyme), a Phase 2 clinical trial was started in December 2002. Patients enrolled into the trial had to meet strict entry criteria and were treated with up to three annual doses of Campath-1H. 探花直播effects of the drug were measured three years after the initial treatment and, unusually for a Phase 2 trial, its effects were compared with the effects of another drug 鈥� interferon beta-1a, the current gold standard treatment for MS. 鈥榃e set the bar high in this trial,鈥� says Enyedy. 鈥楳ost studies of treatments for MS compare the new treatment with a placebo and only last a year.鈥� Genzyme, adds Compston, 鈥榟as been fantastically committed to the development of Campath-1H for use in MS.鈥�

探花直播results of the trial, which were published in 2008 in theNew England Journal of Medicine, showed that there were 70% fewer relapses and that the risk of accumulated disability was 70% lower among the patients receiving Campath-1H than among those treated with interferon beta-1a. Furthermore, as in the patients treated before the trial started, the disability score of patients treated with Campath-1H actually improved; by contrast, it worsened in the patients given interferon beta-1a.

Two large Phase 3 trials are now under way that will finish in 2011. If all goes well, Genzyme expects to apply for marketing approval in 2012, 21 years after the first patient with MS was treated with Campath-1H (and 33 years after Waldmann鈥檚 team started the research that produced Campath-1H). 鈥楽o far, 鈥� says Compston, 鈥榳e have spent 18 years carefully observing treated patients and learning from our mistakes鈥� With more secure funding for our basic and clinical research in the 1990s, we might have been able to move more quickly. But with a disease like MS, which was then poorly understood, it was always going to take a long while to develop a new drug.鈥� Importantly, adds Enyedy, 鈥榠f the Phase 3 trials are successful, I think we can stake a claim for a new standard of care for a large subset of patients with relapsing鈥搑emitting MS,鈥� a prospect that, Compston says, is 鈥榲ery rewarding for a clinical neurologist who has seen so many young people lose the ability to perform simple aspects of everyday living as a result of this difficult disease.鈥�

Glossary

Antibody: a secreted protein made by the immune system that binds to a specific molecule called its antigen. Antibody binding to an antigen on the surface of pathogens (disease-causing organisms) recruits other parts of the immune system to kill the pathogen. Antibodies are members of a family of proteins called immunoglobulins (Ig).

Antigen: any molecule that can bind specifically to an antibody.

Autoimmune disease: a disease in which the immune system mounts a response against self antigens.

B lymphocyte: a type of white blood cell that makes antibodies.

Bone marrow: the spongy material inside bones where all the cells in the blood, including red blood cells and lymphocytes, are made.

Complement: a set of blood proteins that form one of the immune system鈥檚 mechanisms for killing pathogens.

Isotypes: different classes of immunoglobulins such as IgG and IgM. Some of the isotypes have subclasses. For example, there are four human IgG subclasses 鈥� IgG1, IgG2, IgG3 and IgG4.

Monoclonal antibodies: antibodies that are made artificially in the laboratory.

Self antigens: molecules that are in an individual鈥檚 own tissues.

T lymphocytes: a type of white blood cell that helps B lymphocytes make antibodies and that also directly kills pathogen-infected cells.

Tolerance: the failure to respond to an antigen. 探花直播immune system is usually tolerant to self antigens.

聽

探花直播path from innovation to impact can be long and complex. Here we describe the 30-year journey behind the development of a drug now being used to treat multiple sclerosis.

As in other diseases, the development of Campath-1H for the treatment of MS has relied on academic researchers willing to do the basic research needed to understand how Campath-1H is working in patients and how to make it more effective.

Photograph: Greg Smolonski

Waldmann, Clark and Hale

A tale of two innovations

We are often taken aback by the sudden appearance of a new innovation that has clear economic or clinical impact. Just how did these innovations arise?

Academic scientists working in universities are driven to do their research for many reasons. Some see their research as a way to develop new drugs or to build more powerful computers, for example. Many academic scientists, however, are simply curious about the world around them. They may want to understand the intricacies of the immune system or how the physical structure of a material determines its properties at a purely intellectual level. They may never intend to make any practical use of the knowledge that they glean from their studies.

Importantly, however, even the most basic, most fundamental research can be the starting point for the development of materials and technologies that make a real difference to the everyday life of ordinary people and that bring economic benefit to the country. Indeed, said Dr Richard Jennings, Director of Technology Transfer and Consultancy Services at Cambridge Enterprise Ltd, 探花直播 of Cambridge, 鈥榳hat universities are good at is fundamental research and it is high-quality basic research that generates the really exciting ideas that are going to change the world.鈥�

But it takes a great deal of time, money and commitment to progress from a piece of basic research to a commercial product, and the complex journey from the laboratory to the marketplace can succeed only if there is long-term governmental support for the academic scientists and their ideas as well as the involvement of committed commercial partners and well-funded technology transfer offices.

Two particular stories illustrate the long and complex path taken from the laboratory to commercial success by two very different 探花直播 of Cambridge innovations. In the case of Plastic Logic, basic research on materials called organic semiconductors that started in the 1980s and that continues today has led to the development of a new type of electronic reader that should be marketed in early 2010 and, more generally, to the development of 鈥榩lastic electronics鈥�, a radical innovation that could eventually parallel silicon-based electronics. For Campath, the journey started just before Christmas in 1979 in a laboratory where researchers were trying to understand an immunological concept called tolerance. Now, nearly three decades later and after a considerable amount of both basic research and commercial development, Campath-1H is in Phase 3 clinical trials for the treatment of relapsing鈥搑emitting multiple sclerosis.

鈥楤oth innovations are likely to have profound impacts over the next two years and it is important to recognise the deep temporal roots of both,鈥� said Professor Ian Leslie, Pro-Vice-Chancellor for Research.

Professor Leslie highlighted that an important lesson to draw from these stories 鈥榠s the need for universities and other recipients of public research funding to implement and develop processes to support the translation of discovery to impact or, more generally, to develop environments in which the results of discovery can be taken forward and in which external opportunities for innovation are understood.鈥�

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A brain chemical changes locusts from harmless grasshoppers to swarming pests

bjb42 — Fri, 30 Jan 2009 00:00:00 +0000

A collaboration between a team of scientists in Cambridge and Oxford, UK and Sydney, Australia has identified an increase in the chemical serotonin in specific parts of the insects' nervous system as initiating the key changes in behaviour that cause them to swarm.

Desert Locusts are one of the most devastating insect pests, affecting 20% of the world's land surface. Vast swarms containing billions of locusts stretching over many square kilometres periodically devastated parts of the USA at the time of the settlement of the West, and continue to inflict severe economic hardship on parts of Africa and China. In November 2008 swarms six kilometres (3.7 miles) long plagued Australia.

Locusts belong to the grasshopper family but unlike their harmless relatives they have the unusual ability to live in either a solitary or a gregarious state, with the genetic instructions for both packaged within a single genome.

Locusts originate from barren regions that see only occasional transient rainfalls. While unforgiving conditions prevail, locusts eke out a living as solitary individuals with a strong aversion to mingling with other locusts. When the rains come, the amount and quality of vegetation expands and the locusts can breed in large numbers.

In deserts, however, the rains are not sustained and food soon becomes more and more sparse. Thus large numbers of locusts are funnelled into dwindling patches of remaining vegetation where they are forced into close contact with each other. This crowding triggers a dramatic and rapid change in the locusts' behaviour: they become very mobile and they actively seek the company of other locusts. This new behaviour keeps the crowd together while the insects acquire distinctly different colours and large muscles that equip them for prolonged flights in swarms.

As Steve Rogers from Cambridge 探花直播 emphasises: " 探花直播gregarious phase is a strategy born of desperation and driven by hunger, and swarming is a response to find pastures new."

Solitary and gregarious locusts are so different in looks and behaviour that they were thought to be separate species until 1921. But the realisation that crowding triggers swarming posed a new problem: how can the mere presence of other locusts have such a dramatic effect?

探花直播new research, which was funded by the Biotechnology and Biological Sciences Research Council, the Natural Sciences and Engineering Research Council of Canada and the Royal Society, solved this 90 year old question by identifying an increase in the chemical serotonin in specific parts of the locust's nervous system as launching the fundamental changes in behaviour that lead to the gregarious phase.

In the laboratory, solitary locusts can be turned into gregarious ones in just two hours simply by tickling their hind legs to simulate the jostling that locusts experience in a crowd. This period coincides with a threefold but transient (less than 24 hours) increase in the amount of serotonin in the thoracic region of the nervous system. Experiments were then designed to show that serotonin is indeed the causal link between the experience of being in a crowd and the change in behaviour.

First, locusts were injected with specific chemicals that block the action of serotonin on its receptors: when these locusts were exposed to the same gregarizing stimuli, they did not become gregarious. Second, chemicals that block the production of serotonin had the same effect. Third, when injected with serotonin or chemicals that mimic serotonin, locusts turned gregarious even in the absence of other locusts. Finally, chemicals that increased the natural synthesis of serotonin enhanced gregarization when locusts were exposed to the tickling stimuli. This indicates that it is the synthesis of serotonin that is driven by these specific stimuli and in turn changes the behaviour.

Dr Michael Anstey, an author of the paper from the 探花直播 of Oxford, said:

"Up until now, whilst we knew the stimuli that cause locusts' amazing 'Jekyll and Hyde'-style transformation, nobody had been able to identify the changes in the nervous system that turn antisocial locusts into monstrous swarms. 探花直播question of how locusts transform their behaviour in this way has puzzled scientists for almost 90 years, now we finally have the evidence to provide an answer."

Dr Swidbert Ott, from Cambridge 探花直播, one of the co-authors of the article, said: "Serotonin profoundly influences how we humans behave and interact, so to find that the same chemical in the brain is what causes a normally shy antisocial insect to gang up in huge groups is amazing."

Professor Malcolm Burrows, also from Cambridge 探花直播: "We hope that this greater understanding of the mechanisms causing such a big change in behaviour will help in the control of this pest, and more broadly help in understanding the widespread changes in behavioural traits of animals."

Professor Steve Simpson of Oxford and Sydney Universities said: "No other biological system is understood from nerve cells to populations in such detail or to such effect: locusts offer an exemplar of the how to span molecules to ecosystems - one of the greatest challenges in modern science."

Photo by Tom Fayle (Cambridge 探花直播) and provided by Science.

Scientists have uncovered the underlying biological reason why locusts form migrating swarms. Their findings, reported in today's edition of Science, could be used in the future to prevent the plagues which devastate crops (notably in developing countries), affecting the livelihood of one in ten people across the globe.

Up until now, whilst we knew the stimuli that cause locusts' amazing 'Jekyll and Hyde'-style transformation, nobody had been able to identify the changes in the nervous system that turn antisocial locusts into monstrous swarms.

Dr Michael Anstey

Leo-seta from Flickr

Grasshopper

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Yes

New hopes for the nervous system: multiple sclerosis

amb206 — Thu, 01 Jan 2009 00:00:00 +0000

Multiple sclerosis (MS) affects almost 100,000 people in the UK and several million worldwide, many of whom develop the illness between the ages of 20 and 40. Individuals at first experience episodes that transiently disturb functions that healthy people take for granted: seeing, walking, feeling, thinking and emptying the bladder. Later, the episodes are replaced by secondary progression and, as the disabilities mount up, the illness begins to threaten many aspects of daily living.

MS results when the body mounts an autoimmune attack on nerve fibres, particularly targeting the myelin sheath that envelops them and interfering with the passage of the nerve impulse through the spinal cord and brain. 探花直播prime orchestrator of this damage has been identified 鈥� a type of white blood cell known as the T cell 鈥� but exactly how tissue injury occurs, why there is a characteristic relapsing鈥搑emitting pattern followed by secondary progressive disease, and how to treat the illness effectively, have remained elusive.

Made in Cambridge

探花直播results of a recent study raise new hopes for patients with MS. A three-year, Phase 2 clinical trial with Alemtuzumab (also known as Campath), in which over 300 patients were treated, showed that not only was the advance of disease halted but, remarkably, many patients started to get better 鈥� perhaps due to brain repair. Professor Alastair Compston and Dr Alasdair Coles in the Department of Clinical Neurosciences found that the drug reduced the relapse rate by an additional 74% compared with the standard treatment, and the risk of accumulating fixed disability also fell by 71%.

These results provide a new installment in what has been a fascinating history for an antibody made in Cambridge in 1979 by Professor Herman Waldmann in the Department of Pathology. Campath was the first antibody to be 鈥榟umanised鈥� 鈥� a technique pioneered by Dr Greg Winter at the Medical Research Council Laboratory of Molecular Biology that minimises the risk of the drug being rejected as foreign when given to patients. Because the drug destroys white blood cells, it has been principally used to treat adult leukaemia, a disease in which abnormal white blood cells build up and fatally 鈥榗rowd out鈥� normal, healthy blood cells. This lymphocyte-destroying ability is now being exploited to destroy the perpetrators of havoc in MS.

Surprisingly, given that the drug is known to destroy white blood cells, infections were only slightly more common after treatment with Campath. Instead, the development of another autoimmune disease 鈥� usually affecting the thyroid gland 鈥� proved to be the major, and unexpected, complication.

All in the timing

Although Campath鈥檚 potential as a treatment for MS was first considered 18 years ago in Cambridge, early attempts to treat patients who had already reached the secondary progressive stage failed to improve their worsening disabilities. It seems that it鈥檚 all in the timing. 探花直播results of this latest study have shown that the drug must be given early, before the destruction of the myelin sheath has advanced to the point that secondary damage to the underlying nerves continues unabated. Not only does this strategy head off sustained accumulation of disability but it also allows some existing damage to get better, a factor not seen in any previous clinical trials. Expectations are high that the Phase 3 trials, now in progress, will lead to drug registration within a few years.

For more information, please contact the author Professor Alastair Compston (alastair.compston@medschl.cam.ac.uk) at the Department of Clinical Neurosciences. This research was published in聽New England Journal of Medicine(2008) 359, 1786鈥�1801 and was funded by Genzyme and Bayer Schering Pharma AG.

Cambridge neurologists have shown that an antibody used to treat leukaemia also limits and repairs the damage in multiple sclerosis.

探花直播results of this latest study have shown that the drug must be given early, before the destruction of the myelin sheath has advanced to the point that secondary damage to the underlying nerves continues unabated.

Jon Heras, Equinox Graphics

Nerve cell

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Yes