The future of chronic spinal cord injury repair a focus on chondroitinase

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1 Research Reception The future of chronic spinal cord injury repair a focus on chondroitinase Wednesday 7 th November 2012 King s College London Sponsored by

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3 Research Reception Welcome to our Research Reception on The future of chronic spinal cord injury repair a focus on chondroitinase. We are delighted that so many of you could attend this evening to learn more about our research, in particular the very promising therapy involving the bacterial enzyme chondroitinase. This evening you will hear from Dr Elizabeth Bradbury, a leading expert in central nervous system regeneration in the spinal cord, and her work involving chondroitinase. She has shown that treatment with chondroitinase reduces scarring, promoting axon regeneration and partial recovery following spinal cord injury in an animal model. You will also hear from our Director of Research, Dr Mark Bacon, who will talk about our role in accelerating the progress towards treatments and the importance and progress made in influencing the research agenda here in the UK and worldwide. A number of Spinal Research-funded PhD students and researchers from King s College will be at tonight s reception, so please take the opportunity to speak to them, ask questions and learn more about their work. Five poster presentations on the work they are undertaking will also be available to view. We hope you enjoy this evening s reception and are able to learn more about our work as we draw ever closer to human clinical trials. Many thanks for your support now and in the future. Jonathan Miall Chief Executive Spinal Research

4 A focus on chondroitinase At Spinal Research our aim is to find an effective treatment for spinal cord injury that not only improves sensation and movement for people living with paralysis, but brings us closer to a day when we finally conquer it. Thirty years ago spinal cord injury was considered incurable and few people, if any, were contemplating research into repair. Today we are standing on the brink of clinical trials of therapies that will restore movement and feeling and transform the lives of paralysed people. Significant successes in our research mean that we have identified chondroitinase as a treatment, proven in the laboratory, with the potential to prevent or reverse paralysis following a spinal injury. Chondroitinase is a bacterial enzyme which is able to digest the scar tissue that impedes nerve regeneration and stifles changes needed for effective rehabilitation. We are currently looking to modify this enzyme into a form that is safe for use in humans. This will be a significant step forward and will open the way to clinical trials using this treatment. Our experience of chondroitinase illustrates there is a window of opportunity to enhance beneficial plasticity; a time when new connections can be made and function recovered. At a fundamental level, enhancing plasticity may also offer therapeutic opportunities in other neurological disorders such as stroke, traumatic brain injury, blindness and even impaired memory to name a few. A key priority for the future is to bring the first plasticity treatment to the clinic. The following research projects involving chondroitinase are currently being funded by Spinal Research: Development of the enzyme chondroitinase for use in clinical trials with spinal cord injury Dr Elizabeth Muir, Professor Roger Keynes and Professor James Fawcett, Cambridge Centre for Brain Repair, UK The aim of this project is to modify the chondroitinase enzyme into a form that is safe for use in humans so that it can be taken into clinical trials. So far this project has produced fantastic results which have already exceeded our initial expectations. The team has shown that treated animal models have reduced scarring, preserved nerve function in the injury zone and demonstrated better recovery of normal movements. These results indicate that this new method for the treatment of spinal cord injury holds great promise, and has generated much excitement in the scientific community. The next stage is to drive this research forward and take chondroitinase to clinical trials.

5 Chondroitinase Steering Group As a result of the success of the Muir and Fawcett project, Spinal Research is now entering a clinical development phase for this exciting therapeutic concept. It has brought together six leading figures in the field of chondroitinase research to formulate a detailed development plan outlining the essential criteria and milestones this new treatment must achieve in order to enter a first in man study. The team will establish the target patient group, the best course of development, the most effective method of delivery and the quickest route to clinical trials. They will also look at budget requirements and how to sustain this ambitious programme through to safe application to those living with a spinal cord injury. The steering group will include: Dr Elizabeth Bradbury Kings College, London. Professor Jerry Silver Case Western Reserve University, USA. Dr Silver s team have recently shown an 80-90% restoration of breathing in the laboratory using chondroitinase. Professor James Fawcett University of Cambridge, Centre for Brain Repair. Professor Fawcett was part of the team which first developed chondroitinase. Dr Liz Muir University of Cambridge. Dr Joost Verhaagen Netherlands Institute for Neuroscience, Netherlands. The team will use the viral vectors developed by Dr Verhaagen. Professor Armin Curt University Hospital Balgrist, Zurich. Professor Curt is a leading scientist in Europe and will help to lay the path for clinical trials. Dr James Guest Miami Project to Cure Paralysis, USA. Dr Guest has previous experience of applying for and conducting clinical trials in America. Dr Mark Bacon Director of Research, Spinal Research.

6 Nathalie Rose Barr Studentships To sustain the future of our research into spinal cord repair, we encourage the development of talented, highly-motivated young scientists in both clinical and basic science research. The following projects involve chondroitinase: Maximising recovery of function after spinal cord injury with a combination of electrical stimulation and chondroitinase Dr Ronaldo Ichiyama, University of Leeds The project is looking at the effects of epidural electrical stimulation combined with the delivery of chondroitinase. Epidural stimulation has already been shown to promote locomotor function, and chondroitinase is widely recognised as one of the most promising therapies for spinal cord repair. Dr Ronaldo Ichiyama and his team will test the optimum timing and method of delivery for this type of combined treatment, which is a precursor to successful universal treatments for people living with paralysis both for the newly injured and those living with longer-term spinal cord injury. Combinatorial treatment to regulate scar formation and promote regeneration in spinal cord injury Professor Arthur Butt, University of Portsmouth, in collaboration with Dr Elizabeth Bradbury This project involves two of the leading experts in their fields. Dr Bradbury s work has already shown that treatment with the enzyme chondroitinase ABC (ChABC) promotes axon regeneration and partial recovery following spinal cord injury in an animal model. Professor Butt has shown that another enzyme called glycogen synthase kinase (GSK3β) triggers profound changes in cellular composition and that inhibiting production of GSK3β stimulates axon regeneration in spinal cord injury. This project will therefore look at the effects of GSK3β inhibition on scar formation and axon regeneration following spinal cord injury, both singly and in combination with ChABC. It is predicted that combined treatments will promote targeted regeneration to a greater extent than single treatments. It is important to determine the effectiveness of combinatorial strategies in maximising the extent of repair, with the ultimate aim of being able to translate these findings into treatments for spinal cord injured patients.

7 Programme This evening is your opportunity to speak to some of our researchers about the work they are undertaking, what they are hoping to achieve and what this could mean for people living with a spinal cord injury. Six laboratory tours will be taking place throughout the evening, each featuring two different demonstrations given by PhD students. The first demonstration is given by Nick James and Emily Burnside on assessing recovery of function following spinal cord injury. The second is given by Katalin Bartus and Claudia Kathe on assessing regeneration and repair following spinal cord injury. Additionally, Elisabeth Thubron and Stephanie Maynard will be using the cryostat and vibratome to demonstrate how the team cuts ultra thin sections of spinal cord tissue in preparation for the anatomical assessments Laboratory tour 1 (Red Group) Laboratory tour 2 (Green Group) Laboratory tour 3 (Yellow Group) Laboratory tour 4 (Blue Group) Presentation Jonathan Miall, Chief Executive, Spinal Research Dan Eley, Spinal Research supporter Dr Mark Bacon, Director of Research, Spinal Research Dr Elizabeth Bradbury, Senior Fellow, King s College London Laboratory tour 5 (Black Group) Laboratory tour 6 (Purple Group)

8 Speakers Dr Mark Bacon Mark has spent over 20 years as an academic and commercial scientist. His research interests have included the study of membrane transport proteins, photosensitive bacterial proteins for optical computing, targeted drug delivery to the spinal cord and brain as well as the development of specialised agents to enhance neurological imaging. In 2007 Mark joined Spinal Research where he has been charged with developing a translational strategy for the charity that will accelerate the rate of approach of basic science towards the clinic. Dr Elizabeth Bradbury Elizabeth Bradbury attained her PhD at the Institute of Psychiatry, University of London, where her research was focused on brain repair and neural transplantation. She then moved to the Department of Physiology at St Thomas Hospital where she began studying strategies to promote repair following spinal cord injury. Her post-doctoral research was focused on neurotrophic factors (proteins responsible for the growth and survival of neurons) as a therapeutic strategy for promoting neuroprotection (protection of the nerves) and regeneration following spinal cord injury. She then began focusing on inhibitory factors which prevent nerve regeneration after spinal cord injury. This led to the discovery that an enzyme called chondroitinase could promote recovery of motor function following spinal cord injury in experimental animals. This work was published in the journal Nature in 2002 and has had a big impact in the field of spinal cord injury research, with chondroitinase therapy now a leading candidate for clinical trials. Dr Bradbury was awarded the Schellenberg Prize for Research in 2008 by the International Foundation for Research in Paraplegia for her work on chondroitinase and her contribution to spinal cord injury research. She has recently been awarded a Medical Research Council Senior Non-Clinical Fellowship to fund a five-year programme of research to develop new therapies aimed at maximising the function of spared spinal axons and improving spinal conduction in clinically relevant models of spinal cord injury.

9 Meet the researchers Professor Stephen McMahon Professor McMahon is Sherrington Professor of Physiology at King s College London and Director of the London Pain Consortium. He is a neuroscientist who trained with Patrick Wall in the 1980s. He is principally interested in somatosensory systems (part of the sensory system concerned with the conscious perception of touch, pain, temperature, etc.) and actively engaged in work ranging from molecular biology to electrophysiology and human psychophysical studies. He has published more than 250 original research articles and is co-editor of the Textbook of Pain. His work has been published in leading scientific journals including Nature, Nature Medicine, Science and Nature Neuroscience. A major interest of his laboratory relates to repair of the damaged spinal cord. He is actively exploring potential therapies based on enhancing growth capacity of damaged central nervous system neurons (CNS) and overcoming the inhibitory environment which blocks regeneration in the damaged CNS. Professor McMahon is the holder of a Wellcome Trust Senior Investigator Award and a Fellow of the Academy of Medical Sciences. He has served on the Scientific Committee of Spinal Research for a number of years. Dr Lawrence Moon Dr Moon specialises in neural repair, including spinal cord injury and brain injury (stroke). He obtained a first class degree from the University of Oxford in Psychology, Physiology and Philosophy, and then completed a PhD in the laboratory of Professor James Fawcett at the Centre for Brain Repair in Cambridge. He then worked as a postdoctoral researcher in the laboratory of Professor Mary Bunge at the Miami Project to Cure Paralysis in the USA before returning to the UK in 2005 to take up a position at King s College London. Dr Moon and his team collaborate with several other investigators at King s College, including Professor Steve McMahon and Dr Elizabeth Bradbury, and use a range of cutting-edge methods such as functional brain imaging and neural recording from the spinal cord, muscles, nerves and brain in their work.

10 Poster presentations The following poster presentations will be given by Dr Lawrence Moon, Professor Stephen McMahon, Athanasios Didangelos, Karen Bosch and Tom Hutson. Titles: Gene delivery of chondroitinase ABC promotes functional repair following contusion injury at thoracic or cervical level. Gene delivery of chondroitinase ABC reduces secondary pathology and alters inflammatory events following spinal cord injury. Neuregulin-1 plays a role in Schwann cell migration and axonal remyelination following spinal cord injury. Laser microdissection of in vivo regenerating spinal neurons identifies genes, including ptpn2, that promote neurite outgrowth. Peripheral delivery of recombinant neurotrophin-3 for spinal cord injury.

11 Universa Law We are delighted to be supporting Spinal Research whose work gives hope to the lives of our seriously injured clients and it is of vital importance that their outstanding research continues to gain momentum over the coming years. Paul Cairaschi, Director and Principal Solicitor at Universa Law Universa Law Solicitors are specialists in handling serious head and spinal injury cases on behalf of those injured as a result of another's negligence. They see the devastating effect that such injuries have on the lives of their clients and strive to make improvements by seeking funding for: interim payments for clients as a result of not being able to work full assessment and provision of intensive rehabilitation home adaptations / purchase of single storey dwelling all treatment / rehabilitative needs full compensation for all injuries and future needs and future loss of earnings / pension rights. For further information, visit or call Universa Law are members of The Law Society Personal Injury Panel and Association of Personal Injury Lawyers. Head and spinal injury cases require special knowledge and expertise so that the future financial and medical requirements of those involved are properly provisioned.

12 About Spinal Research Spinal Research is the UK s leading and most influential spinal cord repair charity. We set the standard for spinal cord research across the world and are at the forefront of developing strategies for repair. We receive no government funding and are entirely dependent on donations from individuals, companies and charitable trusts, as well as gifts in people s wills. Leading the way We fund more research into the repair of spinal cord injury than any other charity in the UK and aim to build on our achievements year after year until we find an effective treatment for spinal cord injury. Over the last 30 years, we have achieved a number of groundbreaking changes in the field and are ever closer to translating laboratory findings into therapies for real people. Our priority now is to develop a UK Translational Research Network for spinal cord injury repair, providing a world class resource that will change the lives of people affected by spinal cord injury. Influencing the research agenda As a founding member and current chair of the International Campaign for Cures for spinal cord injury Paralysis (ICCP), we have played a significant role in the development of the ICCP Clinical Trials Guidelines for spinal cord injury a global reference standard. We continue to exert influence amongst international stakeholders and collaborate with medical research charities and networks worldwide. We work with other foundations both here and abroad to develop strategic alliances by co-funding initiatives and peer reviews to create critical capital for larger and longer-term research programmes and to reduce unnecessary duplication of activity. We also contribute to the wider debate surrounding medical research by participating in the Medical Research Council, the Association of Medial Research Charities and the United Kingdom Spinal Cord Injury Research Network. A recent working partnership with the National Spinal Cord Injury Strategy Board culminated in the development of a national patient registry and clinical outcomes database which will be used by the spinal injury units across the UK to collect information on the patient care pathway. This is an important first step towards the establishment of successful clinical trials in the near future and will put the UK at the forefront of clinical research in spinal cord injury.

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14 Spinal Research 8a Bramley Business Centre Station Road Bramley Guildford Surrey GU5 0AZ Tel: Visit:

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