̽��ֱ�� of Cambridge - Robin Franklin

Nine Cambridge scientists among the new 2022 Fellows announced by the Royal Society

jg533 — Tue, 10 May 2022 11:33:12 +0000

̽��ֱ��Royal Society is a self-governing Fellowship made up of the most eminent scientists, engineers and technologists from the UK and the Commonwealth. Its Foreign Members are drawn from the rest of the world.

̽��ֱ��Society’s fundamental purpose is to recognise, promote, and support excellence in science and to encourage the development and use of science for the benefit of humanity.

This year, a total of 51 Fellows, 10 Foreign Members, and one Honorary Fellow have been selected for their outstanding contributions to science.

Sir Adrian Smith, President of the Royal Society said: “It is an honour to welcome so many outstanding researchers from around the world into the Fellowship of the Royal Society.

“Through their careers so far, these researchers have helped further our understanding of human disease, biodiversity loss and the origins of the universe. I am also pleased to see so many new Fellows working in areas likely to have a transformative impact on our society over this century, from new materials and energy technologies to synthetic biology and artificial intelligence. I look forward to seeing what great things they will achieve in the years ahead.”

̽��ֱ��Cambridge Fellows are:

Professor Graham Burton FMedSci FRS

Mary Marshall and Arthur Walton Professor Emeritus of the Physiology of Reproduction, ̽��ֱ�� of Cambridge

Burton is a reproductive biologist whose research has focused on the early stages of human pregnancy. In particular, he showed how the placenta is established in a protective low-oxygen environment, stimulating its own development through interactions with the uterus. He demonstrated that aberrations in the early stages of placental development can adversely affect the life-long health of mother and offspring. Burton was founding Director of the Centre for Trophoblast Research, and founding Chair of the Strategic Research Initiative Cambridge Reproduction.

He said: “I am delighted to receive this recognition for myself and the field of reproductive biology, and thank colleagues and collaborators for their contributions over the years.”

Professor Roberto Cipolla FREng FRS

Professor of Information Engineering, Department of Engineering, ̽��ֱ�� of Cambridge

Cipolla is distinguished for his research in computer vision and his contributions to the reconstruction, registration and recognition of three-dimensional objects from images. These include novel algorithms for the recovery of accurate 3D shape, visual localisation and semantic segmentation and their translation into commercial products.

He said: "This is the ultimate honour for any scientist and recognises the amazing contribution of my students, collaborators and mentors in my 30 years at Cambridge. I am also very fortunate to be working in the field of computer vision and machine learning at a time of revolutionary progress and ground-breaking applications.”

Professor Douglas Easton FMedSci FRS

Professor of Genetic Epidemiology, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, ̽��ֱ�� of Cambridge

Easton’s main research interests are in cancer genetics. He analyses large population studies to identify genetic variants that predispose to cancer, and to understand how they combine together with other factors to determine cancer risk. His work has characterised many important cancer genes such as BRCA1 and BRCA2, and identified of hundreds of common cancer predisposition variants in the non-coding genome. He co-developed the BOADICEA risk prediction model now used worldwide to guide genetic counselling and cancer prevention.

He said: "I am truly delighted and honoured to be elected to the Fellowship of the Royal Society. This prestigious honour is a tribute the work of many wonderful colleagues in Cambridge and worldwide, over many years, who have made the research possible."

Professor Robin Franklin FMedSci FRS

Formerly Professor of Stem Cell Medicine, Wellcome - MRC Cambridge Stem Cell Institute, ̽��ֱ�� of Cambridge; now Principal Investigator, Altos Labs - Cambridge Institute

̽��ֱ��central question of Franklin’s career is 'how do tissues regenerate?' To address this question, he has studied the brain, an organ notorious for its poor regenerative capacity. Working with many excellent colleagues, he has described how stem cells in the adult brain regenerate oligodendrocytes - the cells responsible for making the insulating myelin sheath around nerve fibres - once they are lost in diseases such as multiple sclerosis (MS); how this process declines with age; and it can be reversed. ̽��ֱ��work has led to two regenerative medicine trials in MS.

He said: “I am absolutely delighted to have been elected a Fellow of the Royal Society - it is a huge honour.”

Professor Richard Gilbertson FMedSci FRS

Li Ka Shing Chair of Oncology and Head of Department of Oncology, ̽��ֱ�� of Cambridge, Director of Cancer Research UK Cambridge Centre and Senior Group Leader, Cancer Research UK Cambridge Institute

Gilbertson, a paediatric physician-scientist, has identified the origins of common and aggressive childhood brain tumours and many of the genetic alterations that drive these tumours. His research has helped establish a direct link between disordered development and the multiple different brain tumour types observed in children: contributing directly to their classification by the World Health Organisation (WHO); changing the way conventional treatments are used, sparing children from unnecessary side effects; and underpinning clinical trials of new therapies.

Gilbertson said: “I am truly delighted and humbled to receive this recognition that I share with all the wonderful students, trainees and colleagues I have worked with over the years.”

Professor Paul Lehner FMedSci FRS

Professor of Immunology and Medicine, Cambridge Institute for Medical Research, ̽��ֱ�� of Cambridge

Lehner studies virus-host antagonism and how our genome is defended from invasion by RNA-derived retroelements such as HIV. His discovery of the ‘HUSH’ epigenetic silencing complex explains how the genome distinguishes new genetic material from endogenous genes through recognition of intronless DNA. This work uncovered an unanticipated surveillance system that discriminates ‘self’ from ‘non-self’ genomic DNA and defends our genome against the reverse flow of genetic information (RNA to DNA), paving the way to novel applications in medicine and biotechnology.

Lehner said: “I’m absolutely delighted to be elected to the Fellowship of the Royal Society; I’ve been fortunate to work with incredibly talented people and this honour recognises the commitment of the many past and present members of my group who have contributed to our work.”

Professor Roberto Maiolino FRS

Director of the Kavli Institute for Cosmology and Professor of Experimental Astrophysics, ̽��ֱ�� of Cambridge

Maiolino studies the formation of galaxies using observations collected at some of the largest ground-based and space telescopes. He has obtained key results on the interplay between the evolution of galaxies and the supermassive black holes at their centres. He has also investigated the enrichment of chemical elements across the cosmic epochs, as well as the origin and nature of dust particles in the early Universe.

He said: “I am truly honoured by such a prestigious appointment. Being a Fellow of the Royal Society will certainly foster my research activities and will allow me to further promote exciting, cutting-edge projects.”

Professor Angelos Michaelides FRS

1968 Professor of Chemistry, Yusuf Hamied Department of Chemistry, ̽��ֱ�� of Cambridge

Michaelides’ work involves the development and application of theoretical methods to better understand contemporary problems in chemistry, physics, and materials science. His group places a particular focus on developing and applying computer simulation approaches that provide the fundamental molecular-level insight needed to help address contemporary global challenges related to water, energy, and the environment.

He said: “Holy moly! I’m delighted to have been elected an FRS and very grateful to all the outstanding students, post-docs, collaborators, and mentors I’ve had over the years without whom this would never have happened.”

Professor Jason William Chin FMedSci FRS

Head, Centre for Chemical and Synthetic Biology, and Joint Head, Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology; Professor of Chemistry and Chemical Biology, Yusuf Hamied Department of Chemistry, ̽��ֱ�� of Cambridge; Associate Faculty in Synthetic Genomics, Wellcome Sanger Institute

Chin has engineered the genetic code of living cells to synthesise modified proteins and non-canonical polymers. To accomplish this, he created new translational machinery and codons to reprogram the genetic code, going well-beyond prior work using amber suppression. He then completely synthesised a bacterial genome in which he reduced the number of sense codons in its genetic code. ̽��ֱ��codons thus unused were reassigned to encode non-canonical amino acids. Chin's fundamental advances have been widely used to drive discovery, including to define the molecular consequences of post-translational modifications, define protein interactions in cells, and provide mechanistic insight into enzymes.

̽��ֱ��nine Cambridge researchers were all selected for their exceptional contributions to science.

It is an honour to welcome so many outstanding researchers from around the world into the Fellowship of the Royal Society.

Sir Adrian Smith, President of the Royal Society

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, 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.

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Cambridge scientists reverse ageing process in rat brain stem cells

Anonymous — Wed, 14 Aug 2019 17:01:45 +0000

̽��ֱ��results, published today in Nature, have far-reaching implications for how we understand the ageing process, and how we might develop much-needed treatments for age-related brain diseases.

As our bodies age, our muscles and joints can become stiff, making everyday movements more difficult. This study shows the same is true in our brains, and that age-related brain stiffening has a significant impact on the function of brain stem cells.

A multi-disciplinary research team, based at the Wellcome-MRC Cambridge Stem Cell Institute at the ̽��ֱ�� of Cambridge, studied young and old rat brains to understand the impact of age-related brain stiffening on the function of oligodendrocyte progenitor cells (OPCs). These cells are a type of brain stem cell important for maintaining normal brain function, and for the regeneration of myelin – the fatty sheath that surrounds our nerves, which is damaged in multiple sclerosis (MS). ̽��ֱ��effects of age on these cells contributes to MS, but their function also declines with age in healthy people.

To determine whether the loss of function in aged OPCs was reversible, the researchers transplanted older OPCs from aged rats into the soft, spongy brains of younger animals. Remarkably, the older brain cells were rejuvenated, and began to behave like the younger, more vigorous cells.

To study this further, the researchers developed new materials in the lab with varying degrees of stiffness, and used these to grow and study the rat brain stem cells in a controlled environment. ̽��ֱ��materials were engineered to have a similar softness to either young or old brains.

To fully understand how brain softness and stiffness influences cell behavior, the researchers investigated Piezo1 – a protein found on the cell surface, which informs the cell whether the surrounding environment is soft or stiff.

Dr Kevin Chalut, who co-led the research, said: “We were fascinated to see that when we grew young, functioning rat brain stem cells on the stiff material, the cells became dysfunctional and lost their ability to regenerate, and in fact began to function like aged cells. What was especially interesting, however, was that when the old brain cells were grown on the soft material, they began to function like young cells – in other words, they were rejuvenated.”

“When we removed Piezo1 from the surface of aged brain stem cells, we were able to trick the cells into perceiving a soft surrounding environment, even when they were growing on the stiff material,” explained Professor Robin Franklin, who co-led the research with Dr Chalut. “What’s more, we were able to delete Piezo1 in the OPCs within the aged rat brains, which lead to the cells becoming rejuvenated and once again able to assume their normal regenerative function.”

Dr Susan Kohlhaas, Director of Research at the MS Society, who part funded the research, said: “MS is relentless, painful, and disabling, and treatments that can slow and prevent the accumulation of disability over time are desperately needed. ̽��ֱ��Cambridge team’s discoveries on how brain stem cells age and how this process might be reversed have important implications for future treatment, because it gives us a new target to address issues associated with aging and MS, including how to potentially regain lost function in the brain.”

This research was supported by the European Research Council, MS Society, Biotechnology and Biological Sciences Research Council, ̽��ֱ��Adelson Medical Research Foundation, Medical Research Council and Wellcome.

Niche stiffness underlies the ageing of central nervous system progenitor cells, M. Segel, B. Neumann, M. Hill, I. Weber, C. Viscomi, C. Zhao, A. Young, C. Agley, A. Thompson, G. Gonzalez, A. Sharma, S. Holmqvist, D. Rowitch, K. Franze, R. Franklin and K. Chalut is published in Nature.

New research reveals how increasing brain stiffness as we age causes brain stem cell dysfunction, and demonstrates new ways to reverse older stem cells to a younger, healthier state.

...when the old brain cells were grown on the soft material, they began to function like young cells – in other words, they were rejuvenated

Kevin Chalut

Mikey Segel

Aged rat brain stem cells grown on a soft surface (right) show more healthy, vigorous growth than similar aged brain stem cells grown on a stiff surface (left). ̽��ֱ��red marker shows brain stem cells, and the green marker indicates cell proliferation.

Yes

Spinal injury and ‘biorobotic control’ of the bladder

cjb250 — Tue, 16 Feb 2016 13:27:49 +0000

Spinal cord injury is, in many respects, a testosterone disease, says Professor James Fawcett.

What he means by this is that four out of five spinal cord injuries happen to men, and the most common age group is early adulthood. “Men are not good at assessing risk at that age,” he says. “Females are much more sensible.”

It is perhaps not surprising, then, that when asked about their priorities, most quadriplegic people will select a return of sexual function as second after the use of arms and hands. Third on the list, above being able to walk, is a return of bladder and bowel control. “Way down the list is walking, because wheelchairs work reasonably well and patients can get used to using them,” says Fawcett, who heads the John van Geest Centre for Brain Repair at Cambridge.

Restoring bladder and bowel control is a particular challenge, however. Currently, patients have to fill their bladder with botulinum toxin (botox) to paralyse it and catheterise themselves several times a day. This may be the simplest method, but catheterisation can cause infection and scarring in the urethra.

Instead, Fawcett is developing a device based on the ‘Brindley device’, named after physiologist Giles Brindley, who trained at Cambridge after the Second World War. ̽��ֱ��Brindley device is an implant to which an external stimulator is applied manually, causing the bladder to contract and empty itself. It has been used in thousands of patients, but it, too, is not without problems: it necessitates severing sensory nerves from the pelvis into the spinal cord, causing weakening of the pelvic muscles – and loss of sexual function. (For most male patients, Viagra can at least help them maintain an erection, but this is only half the problem. ‘Well OK, doc,’ they say, ‘you’ve given me an erection, but what’s the use if I can’t feel it?’”)

Fawcett and colleagues are developing a ‘biorobotic’ version of the Brindley device that can read signals from the sensory nerves in the pelvis, rather than requiring them to be cut. These signals would stop the bladder emptying itself at embarrassing times, tell the patient how full the bladder is, and allow them to use the electronics to empty it.

̽��ֱ��ability to record signals from individual nerves has applications beyond just bladder control: Fawcett envisioned the technology as enabling patients who had lost a limb – such as soldiers losing arms or legs – to control robotic limbs. “ ̽��ֱ��limbs themselves are quite sophisticated,” he says, “but what doesn’t work at all well is their interface with the nervous system.” ̽��ֱ��technology required for recording signals for a whole limb has proven to be extremely complicated, so the team is looking at the bladder-control device as a simpler demonstration of a proof of concept.

Biorobotics will be one focus of a proposed new Spinal Injury Research Centre to be based at Addenbrooke’s Hospital. Although still at the very early planning stages, the Centre will capitalise on Cambridge’s position as the regional trauma centre for the East of England (even though a lack of facilities means spinal injury patients have to be sent to Stoke Mandeville near Oxford for rehabilitation).

A simplified version of the adapted Brindley device has so far been trialled in around 50 dogs, in whom spinal cord injury is surprisingly common, particularly in dogs with longer spines, such as dachshunds. Many owners of injured dogs want to keep their pets but, as Fawcett explains, “the dogs are perfectly happy to paddle around with wheels under their back legs, but they do so dribbling urine around your house.”

In fact, a randomised controlled trial in 2013 showed that injured dogs may even be able to do away with their wheels. Professor Robin Franklin from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute showed that transplanting cells found in the nasal cavity, known as olfactory ensheathing cells, into the injured spine could help restore movement to the previously paralysed limbs. Although the cell transplant did not restore bowel or bladder control, it was, says Franklin, “a landmark study” that offers the promise of translation into humans. Franklin’s colleague Dr Mark Kotter is currently seeking funding to carry out a trial in humans.

But as Fawcett says, the priority among injured patients is to recover use of their upper limbs. Spinal cord injury causes damage to motor nerve fibres travelling from the brain and to sensory nerve fibres travelling to the brain. Both are structurally different and need to be coaxed to regenerate across the site of the injury – but even getting the nerve fibres to span these couple of centimetres is a challenge.

“ ̽��ֱ��problem is scar tissue,” says Fawcett. “It’s very difficult for nerve fibres to grow through this tissue.” He has identified an enzyme, chondroitinase, which can dissolve scar tissue. ̽��ֱ��enzyme works in rats and is in preclinical development for use in humans by the US biotech company Acorda Therapeutics.

Once the scar tissue has been dissolved, the nerve fibres need to regenerate and make new connections. Although restoring motor nerve fibres is proving a challenge, Fawcett has managed to restore sensory nerve fibres in rats, which is an important start. “Patients need to be able to feel what they’re doing and to sense pain. If they turn on a hot tap, they can easily scald themselves if they can’t feel the heat. And of course, they want sensation back in their genitalia.”

In most spinal cord injuries, some nerve fibres will always survive, and Fawcett believes we may be able to harness these to bypass nerve damage if we can harness a remarkable property of the young brain known as plasticity, which enables new connections to be made as we learn new skills. If a young child receives a spinal injury, their chances of recovery are much better than for an adult as their brain can adapt, but as we age, a cartilage-like coating wraps around nerve fibres, cementing the connections in place. These molecules make it difficult for the brain of an injured adult to find a way to bypass the injury.

“Interestingly,” explains Fawcett, “one of the main constituents of this cartilage is the same as that which blocks nerve growth in scar tissue – and we know we can dissolve this using chondroitinase. This should make rehabilitation – teaching the brain to do useful things again – dramatically more successful.”

Inset image: Credit ̽��ֱ��District.

There are many challenges facing people with spinal cord injury – and walking again is often the least of their problems. Cambridge research could help patients take control of their lives once more.

This should make rehabilitation – teaching the brain to do useful things again – dramatically more successfull.

James Fawcett

Zeevveez

Wheelchair

̽��ֱ��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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Vitamin D could repair nerve damage in multiple sclerosis, study suggests

cjb250 — Mon, 07 Dec 2015 14:00:25 +0000

Researchers, from the MS Society Cambridge Centre for Myelin Repair, identified that the ‘vitamin D receptor’ protein pairs with an existing protein, called the RXR gamma receptor, already known to be involved in the repair of myelin, the protective sheath surrounding nerve fibres.

By adding vitamin D to brain stem cells where the proteins were present, they found the production rate of oligodendrocytes (myelin making cells) increased by 80%. When they blocked the vitamin D receptor to stop it from working, the RXR gamma protein alone was unable to stimulate the production of oligodendrocytes.

In MS, the body’s own immune system attacks and damages myelin, causing disruption to messages sent around the brain and spinal cord; symptoms are unpredictable and include problems with mobility and balance, pain, and severe fatigue. ̽��ֱ��body has a natural ability to repair myelin, but with age this becomes less effective.

Professor Robin Franklin from the MS Society Cambridge Centre for Myelin Repair and the Wellcome Trust-Medical Research Council Stem Cell Institute, who led the study, says: “For years scientists have been searching for a way to repair damage to myelin. So far, the majority of research on vitamin D has looked at its role in the cause of the disease. This work provides significant evidence that vitamin D is also involved in the regeneration of myelin once the disease has started. In the future we could see a myelin repair drug that works by targeting the vitamin D receptor.”

Dr Susan Kohlhaas, Head of Biomedical Research at the MS Society, said: “More than 100,000 people in the UK have multiple sclerosis and finding treatments that can slow, stop or reverse the worsening of disability is a priority for the MS Society. We’d now like to see more studies to understand whether taking vitamin D supplements could, in time, be an effective and safe treatment for people with MS.

She continued: “For now though, this is early stage research that’s been done in the laboratory and more work is needed before we know whether it would hold true in people with MS. It’s not a good idea, however, to be deficient in vitamin D and we’d encourage anybody who thinks they might be to speak to their GP.”

Following this research, scientists will need to understand more about the underlying biology of this receptor before considering how the vitamin D receptor could be safely and effectively targeted in future trials in people with MS.

Reference
Guzman de la Fuente, A et al. Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation. Journal of Cell Biology; 7 Dec 2015

Adapted from a press release by the MS Society

A protein activated by vitamin D could be involved in repairing damage to myelin in people with multiple sclerosis (MS), according to new research from the ̽��ֱ�� of Cambridge. ̽��ֱ��study, published today in the Journal of Cell Biology, offers significant evidence that vitamin D could be a possible treatment for MS in the future.

This work provides significant evidence that vitamin D is involved in the regeneration of myelin once the disease has started

Robin Franklin

Andrew c

Neuron with oligodendrocyte and myelin sheath (edited)

̽��ֱ��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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New treatments for pain and MS being developed in open innovation programme

sc604 — Tue, 25 Jun 2013 07:28:35 +0000

Two revolutionary treatments which could alleviate pain in people with hypersensitivity to heat, and provide a new regenerative therapy with MS sufferers, are being developed by ̽��ֱ�� of Cambridge researchers at Stevenage Bioscience Catalyst (SBC), the UK’s first open innovation bioscience campus.

First announced in 2012, the programme gives ̽��ֱ�� researchers access to the drug development expertise of GSK and other pharmaceutical companies, while giving industry access to Cambridge research and know-how, in order to accelerate the development of new medicines.

There are now two ̽��ֱ�� research projects in place at SBC. Professor Peter McNaughton of the Department of Pharmacology is working on a novel approach to the pain associated with heat. Billions of dollars are spent each year on the treatment of pain, but there is currently no effective treatment for the extreme pain associated with hypersensitivity to heat.

Professor Robin Franklin of the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute is developing a new regenerative therapy for multiple sclerosis (MS). MS affects almost 100,000 people in the UK, 400,000 in the United States and several million worldwide.

“This is a ground-breaking approach to early-stage drug discovery, which is typically enormously time-consuming and expensive,” said Professor McNaughton. “ ̽��ֱ��exchange of scientific ideas and overall atmosphere of collaboration at SBC can help us as researchers, as well as our industrial colleagues, become more efficient in developing new ideas which will lead to better drugs and improved clinical treatments.”

Cambridge is the first university to establish this type of arrangement. Recently, the ̽��ֱ��, in a bid led by ̽��ֱ�� College London, was awarded a share of £50 million in funding from the Higher Education Funding Council for England (HEFCE) to enable the two universities to work together at SBC, in part to establish a range of collaborative training programmes to develop the next generation of entrepreneurial researchers, particularly in drug discovery. ̽��ֱ��collaboration is directly supported by the National Institute for Health Research ̽��ֱ�� College London Hospitals' Biomedical Research Centre, and will be further expanded through UCLPartners.

“Cambridge generates world-leading medical research and clinical insight, and in order to develop that research to the point where it can benefit patients, we work in partnership with industry,” said Professor Sir Leszek Borysiewicz, the ̽��ֱ��’s Vice-Chancellor. “Stevenage Bioscience Catalyst is a strong model for the future of university and industry collaboration.”

SBC brings together academia and industry with the goal of developing new innovations in the life sciences though collaboration. A key element of the open innovation environment fostered through SBC is enabling scientific exchange to flourish without the need for exclusive research collaboration agreements between partners, including GSK. ̽��ֱ��open innovation model allows Cambridge scientists to freely interact with other pharmaceutical biotech, contract research organisations, SBC tenants and academic institutions.

Other universities interested in joining this novel initiative for drug discovery and development are invited to contact Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm, which is facilitating the project, or Stevenage Bioscience Catalyst. It is anticipated that between three and five ̽��ֱ�� research projects will be located at SBC at any one time.

For more information on this story, please contact sarah.collins@admin.cam.ac.uk.

Cambridge researchers developing new therapies as part of a collaborative programme with industry.

Cambridge generates world-leading medical research and clinical insight, and in order to develop that research to the point where it can benefit patients, we work in partnership with industry

Professor Sir Leszek Borysiewicz

Carl Zeiss Microscopy

Neurons, confocal fluorescence microscopy

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First randomised controlled trial to show spinal cord regeneration in dogs

fpjl2 — Mon, 19 Nov 2012 14:54:25 +0000

In a collaboration between the ̽��ֱ��’s Veterinary School and MRC’s Regenerative Medicine Centre, scientists used a unique type of cell to regenerate the damaged part of the dogs’ spines. ̽��ֱ��researchers are cautiously optimistic that the work could have a future role in the treatment of human patients with similar injuries if used alongside other treatments.

Scientists have been aware for over a decade that olfactory ensheathing cells (OEC) might be useful in treating the damaged spinal cord because of their unique properties. ̽��ֱ��cells have the ability to support nerve fibre growth that maintains a pathway between the nose and the brain.

Previous research using laboratory animals has already revealed that OECs can aid regeneration of the parts of nerve cells that transmit signals (axons) so as to form a ‘bridge’ between damaged and undamaged spinal cord tissue. A Phase 1 trial in human patients with SCI established that the procedure is safe.

̽��ֱ��study, published in the latest issue of the neurology journal Brain, is the first double-blinded randomised controlled trial to test the effectiveness of these transplants to improve function in ‘real-life’ spinal cord injury. ̽��ֱ��trial was performed on animals that had spontaneous and accidental injury rather than in the controlled environment of a laboratory, and some time after the injury occurred. This far more closely resembles the way in which the procedure might be used in human patients.

̽��ֱ��34 pet dogs had all suffered severe spinal cord injury. Twelve months or more after the injury, they were unable to use their back legs to walk and unable to feel pain in their hindquarters. Many of the dogs were dachshunds which are particularly prone to this type of injury. Dogs are also more likely to suffer from SCIs because the spinal cord may be damaged as a result of what in humans is the relatively minor condition of a slipped disc.

In the study, funded by the MRC, one group of dogs had olfactory ensheathing cells from the lining of their own nose injected into the injury site. ̽��ֱ��other group of dogs was injected with just the liquid in which the cells were transplanted. Neither the researchers nor the owners (nor the dogs!) knew which injection they were receiving.

̽��ֱ��dogs were observed for adverse reactions for 24 hours before being returned to their owners. From then on, they were tested at one month intervals for neurological function and to have their gait analysed on a treadmill while being supported in a harness. In particular, the researchers analysed the dogs’ ability to co-ordinate movement of their front and back limbs.

̽��ֱ��group of dogs that had received the OEC injection showed considerable improvement that was not seen in the other group. These animals moved previously paralysed hind limbs and co-ordinated the movement with their front legs. This means that in these dogs neuronal messages were being conducted across the previously damaged part of the spinal cord. However, the researchers established that the new nerve connections accounting for this recovery were occurring over short distances within the spinal cord and not over the longer distances required to connect the brain with the spinal cord.

Professor Robin Franklin, a co-author of the study from the Wellcome Trust-MRC Cambridge Stem Cell Institute, ̽��ֱ�� of Cambridge, said: “Our findings are extremely exciting because they show for the first time that transplanting these types of cell into a severely damaged spinal cord can bring about significant improvement. We’re confident that the technique might be able to restore at least a small amount of movement in human patients with spinal cord injuries but that’s a long way from saying they might be able to regain all lost function. It’s more likely that this procedure might one day be used as part of a combination of treatments, alongside drug and physical therapies, for example.”

Dr Rob Buckle, Head of Regenerative Medicine at the MRC, commented: “This proof of concept study on pet dogs with the type of injury sustained by human spinal patients is tremendously important and an excellent basis for further research in an area where options for treatment are extremely limited. It’s a great example of collaboration between veterinary and regenerative medicine researchers that has had an excellent outcome for the pet participants and potentially for human patients.”

̽��ֱ��researchers stress that human patients with a spinal injury rate a return in sexual function and continence far higher than improved mobility. Some of the dogs in the study did regain bowel and bladder control but the number of these was not statistically significant.

Mrs May Hay, owner of Jasper who took part in the trail (and can be seen in the video), said: “Before the trial, Jasper was unable to walk at all. When we took him out we used a sling for his back legs so that he could exercise the front ones. It was heartbreaking. But now we can’t stop him whizzing round the house and he can even keep up with the two other dogs we own. It’s utterly magic.”

Text courtesy of the Medical Research Council

Researchers have shown it is possible to restore co-ordinated limb movement in dogs with severe spinal cord injury (SCI).

Our findings are extremely exciting because they show for the first time that transplanting these types of cell into a severely damaged spinal cord can bring about significant improvement.

Robin Franklin

Cambridge Veterinary School

A dog called Jasper during the trial

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