MS frontiers 2013 brochure


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MS frontiers 2013 brochure

  1. 1. Sofitel London, Heathrow 9-10 May 2013MSFrontiers2013Bringingthe researchcommunitytogether tobeat MSIn association with12 CPD points availableVisit: download the free web app now.MS_FrontiersHandbook_2013v2withSash.indd 1 25/04/2013 11:24
  2. 2. Name Client Name Job Number Filename PublicationIssue Date Materials Due Date Ad Bleed Size Ad Trim Size Ad Live Area SizeInnovating healthcare, improving health.At Novartis, our goal is to provide high-quality healthcaresolutions to address the evolving needs of patients and societyin the UK. We believe that our dedication to innovation andour responsible approach will enable us to fulfill our missionto care for, and provide high quality treatments for, peoplewith Multiple Sclerosis. Novartis is committed to playing apart in supporting those who are affected by the condition.MUL13-C015Date of Preparation April 2013MS_FrontiersHandbook_2013v2withSash.indd 2 25/04/2013 11:24
  3. 3. MS Frontiers programme Contents 3. Contents 4. Welcome 5. Conference Programme 9. Biographies 16. Presentation abstracts 29. Poster abstracts 83. Notes 87. Sponsor information3MS_FrontiersHandbook_2013v2withSash.indd 3 25/04/2013 11:24
  4. 4. 4WelcomeWelcome to MSFrontiers 2013.I was delighted to accept the position of Acting CEO in February, notleast because it has allowed me to see at first hand the dedication andcommitment the research community shows to people affected by MSand the MS Society.At the MS Society we value research because we can see the differenceit makes to people with MS. But we want to make sure that theresearch we fund will have the greatest impact on the lives of thoseaffected by MS. To that end, we’ve launched a new research strategy(running from 2013 to the end of 2017).The strategy was developed in consultation with the research community and people affected byMS. It sets out our priorities for the next five years and outlines where we are with MS research aswell as highlights areas that need focussed attention, such as progressive MS. You can read thestrategy on our website or we have a limited number of copies available atour Information Stand.In parallel to the strategy we are also running a priority setting partnership with the James LindAlliance, Association of British Neurologists, UK MS Nurses Association and the MS TherapyCentres. This partnership will enable people affected by MS and health care professionals to setresearch priorities to funders.The aim will be to come up with a top 10 list of research questions that reflect the needs of peoplewith MS. Following a survey which closed in January, we have developed a ‘long-list’ of researchquestions that people are now free to vote on. If you’d like to find out more about this importantproject and vote on your research priorities please visit our poster for more information.Finally, I hope this MS Frontiers gives you the opportunity to network, learn about the latestfindings in MS research and share your work. We look forward to working with you in years tocome to ultimately reach our aim: To Beat MS.It is an exciting time for MS research with new treatments coming through and new breakthroughson the horizon and I feel privileged to be a part of that. Can I take this opportunity to thank you foryour help, support and interest which is greatly appreciated.With best wishes,PatriciaPatricia GordonActing Chief ExecutiveMS SocietyMS_FrontiersHandbook_2013v2withSash.indd 4 25/04/2013 11:24
  5. 5. 5Conference programmeThursday 9 May09:30-10:30 Registration & refreshments10:30-10:50 Opening address Patricia Gordon, Acting Chief Executive, MS Society Prof. Sir Andy Haines, London School of Hygiene and Tropical Medicine and co-chair of the MS Society Research Strategy Committee10:50-12:30 Inflammation and axonal damage:protective vs detrimental mechanisms Prof. Frauke Zipp, Department of Neurology, JohannesGutenberg University Medical Centre Mainz Pragmatic Exercise Intervention for People with MS:the ExIMS trial Prof. John Saxton, School of Allied Health Professions,University of East Anglia Session chaired by Nick Rijke, Director of Policy andResearch, MS Society12:30-13:30 Lunch13:30-15:30 Parallel sessions A. Mechanisms of axonal damage Chair: Prof Hugh Perry, University of Southampton Invited Speakers: Dr Don Mahad, University of Edinburgh Dr Michael Coleman, The Babraham Institute Prof Sandra Amor, VU University Medical Center B. Risk factors of MS Chair: Prof Gavin Giovannoni, Barts and the London NHS Trust Invited Speakers: Dr Ian Galea, University of Southampton Dr Ruth Dobson, Barts and the London School of Medicine Dr Robyn Lucas, The Australian National University C. Exercise and Physical Activity for People with MS Chair: Dr Lorna Paul, University of Glasgow Invited Speakers: Prof Mathias Maurer, University Hospital Erlangen Dr Ulrik Dalgas, Aarhus University Prof Helen Dawes, Oxford Brookes UniversityMS_FrontiersHandbook_2013v2withSash.indd 5 25/04/2013 11:24
  6. 6. 6Conference programme15:30-17:30 Poster session with refreshments17:30-18:30 Debate session There is compelling evidence that early aggressivetreatment of MS leads to long-term benefits for thepatient and this should be considered the ‘norm’ inclinical practice Chair: Dr Raj Kapoor, National Hospital of Neurology andNeurosurgery, Queen Square, London For the motion: Prof. Gavin Giovannoni, Barts and the London NHS Trust Against the motion: Dr Nikos Evangelou, Queens MedicalCentre, Nottingham Hospitals NHS Trust19:00-20:00 Drinks reception20:00 Conference dinnerMS_FrontiersHandbook_2013v2withSash.indd 6 25/04/2013 11:24
  7. 7. 7Conference programmeFriday 10 May09:00-09:30 Registration refreshments09:30-11:30 Parallel sessions A. Biomarkers and clinical outcome measures:challenges for progressive MS trials Chair: Dr Raj Kapoor, National Hospital of Neurologyand Neurosurgery, Queen Square, London Invited speakers: Prof Richard Ruddick, Cleveland Clinic Prof David Miller, National Hospital for Neurology andNeurosurgery Prof Gavin Giovannoni, Barts and the London School of Dentistry B. Mind and body: The interface betweenpsychological and biomedical in MS Chair: Prof Roger Baker, Bournemouth University Invited speakers: Prof Trudie Chalder, King’s College London Prof Rona Moss-Morris, King’s College London Mr Stuart Nixon, Person with MS and MS Society Trustee C. Innovations in symptom management,care and support Chair: Dr Richard Warner, Gloucestershire Hospitals NHS Foundation Trust Invited speakers: Dr Rosie Jones, Frenchay Hospital Prof. Jon Marsden, University of Plymouth Prof. James Malone-Lee, University College London11:30-11:45 Refreshments11:45-13:30 Strategies for target discovery to promoteremyelination Prof Charles ffrench-Constant, University of Edinburgh Achievements of the MS Register in the firstthree years and future plans Prof. David Ford, University of Swansea Session chaired by JOHN MILLER, MS Society Trustee13:30-14:30 LunchMS_FrontiersHandbook_2013v2withSash.indd 7 25/04/2013 11:24
  8. 8. 8Conference programme14:30-15:30 Ian McDonald Memorial Lecture Mechanisms of tissue injury in Multiple Sclerosis:Lessons for understanding progressive MS Prof Hans Lassmann Center for Brain Research, Medical University of Vienna, Austria Session chaired by Prof. Richard Reynolds, Imperial CollegeLondon15:30-15:45 Close of conferenceMS_FrontiersHandbook_2013v2withSash.indd 8 25/04/2013 11:24
  9. 9. 9BiographiesSpeaker biographiesFrauke Zipp - After studying Medicine in Germany, the USA, Canada and England, Frauke Zipp beganher scientific career at the MPI Martinsried with Hartmut Wekerle in Neuroimmunology. During clinicaltraining with Johannes Dichgans in Tübingen, she was a visiting scientist at the NIH. After a decade atthe Charité, she moved to the Rhine Main Neuroscience Network (rmn2) as Director of the Departmentof Neurology at the University Medical Center Mainz within the Focus Program of TranslationalNeurosciences. She is currently spokesperson of a Collaborative Research Center on Multiple Sclerosis, oneCo-Coordinator of the Competence Network of Multiple Sclerosis, a Council Member of ECTRIMS and aBoard Member of ISNI. In 2014, she will be a chair of the ISNI conference taking place in Mainz (rmn2).John Saxton is a Professor of Clinical Exercise Physiology in the Faculty of Medicine and HealthSciences at the University of East Anglia, Norwich. He is a BASES Accredited Research Physiologist,member of the Physiological Society and has served on Council for the Society for Research inRehabilitation. His research is focused on the role of exercise and other lifestyle factors in the preventionand management of age-related chronic conditions. He has worked with a number of clinical populations,including people with MS, cancer patients and survivors, patients with peripheral vascular disease andchronic heart failure. His research has been funded by the MS Society, the British Heart Foundation,Heart Research UK, Cancer Research UK and the American Institute for Cancer Research. In 2011 hewas the editor of a book entitled “Exercise and chronic disease: an evidence-based approach”, publishedby Routledge, UK.Hugh Perry was appointed Professor of Experimental Neuropathology at the University of Southamptonin 1998. His research interests are in the field of interactions between the immune system and nervoussystem, and in particular how systemic infection and inflammation play a role in driving the progression ofneurodegenerative disease. He has published more than 300 peer-reviewed papers. He is currently Chairof the MRC Neuroscience and Mental Health Board.Don Mahad - I am interested in bioenergetics of progressive multiple sclerosis and my researchfocuses on the role of mitochondria in MS. My lab has made neuropathological observations indicatingaltered metabolism within neuronal cell bodies and demyelinated axons in progressive MS. We areexploring both the cause and consequences of these neuropathological observations with a view toidentifying potential therapeutic agents for progressive MSMichael Coleman did his PhD with Brian Anderton in London on neurofilament phosphorylationbefore moving to a postdoc with Kay Davies in Oxford in human genetics. He then did a secondpostdoc with Hugh Perry in Oxford where he, Laura Conforti and colleagues identified the slow Walleriandegeneration gene (WldS). His independent career took him to Cologne and then back to the UK at theBabraham Institute near Cambridge, where his work has focussed on the mechanism of action of theWldS protein, what it tells us about Wallerian degeneration itself, other proteins that regulate Walleriandegeneration and how to translate this into pharmacological methods to preserve axons. Other interestsinclude the regulation of axonal transport, axon pathology in Alzheimer’s disease and age-related axon loss.MS_FrontiersHandbook_2013v2withSash.indd 9 25/04/2013 11:24
  10. 10. 10BiographiesSandra Amor - My research experience extends across virology, pathology, immunology andneurosciences. I am head of the MS research group in Pathology at VU Medial Centre in Amsterdam.My commitment and dedication to research extends to understanding the needs of people with MS byorganizing interactions between patients and scientists (Meet the Scientist) – for which we were awarded‘Best Information award’ and by MS society in 2009. I am also involved in facilitating public awareness ofdisease including advertising and media. Together with Hans van Noort we have published a book ‘MS –the facts’ by Oxford University Press, centered on the major questions posed to us by people with MS atthe Meet the Scientists forum.My research group of 7 people is focussed on understanding the first steps in lesion formation in MS. Inaddition to studying human tissues have developed models to mimic what we think happens in lesionformation. The studies of brain tissues from people with MS have revealed several new pathways ininnate immune activation in the brain. Some of these are currently being tested in animals in an attemptto modulate the immune responses in the CNS.Gavin Giovannoni was appointed to the Chair of Neurology, Blizard Institute of Cell and MolecularScience, Barts and The London School of Medicine and Dentistry, Queen Mary University of Londonand the Department of Neurology, Barts and The London NHS Trust in November 2006. In September2008 he took over as the Neuroscience and Trauma Centre Lead in the Blizard Institute of Cell andMolecular Science. Gavin did his undergraduate medical training at the University of the Witwatersrand,South Africa, where he graduated cum laude in 1987 winning the prizes for best graduate in medicineand surgery. He moved to the Institute of Neurology, University College London, Queen Square, Londonin 1993 after completing his specialist training in neurology in South Africa. After three years as a clinicalresearch fellow, under Professor Ed Thompson, and then two years as the Scarfe Lecturer, workingfor Professor W. Ian McDonald, he was awarded a PhD in immunology from the University of Londonin 1998. He was appointed as a Clinical Senior Lecturer, Royal Free and University College MedicalSchool, in 1998 and moved back to Institute of Neurology, Queen Square in 1999. He was promoted toReader in Neuroimmunology in 2004. His clinical interests are multiple sclerosis and other inflammatorydisorders of the central nervous system. He is particularly interested in clinical issues related to optimisingMS disease modifying therapies. Gavin’s current research is focused on Epstein Barr virus as a possiblecause of multiple sclerosis, defining the “multiple sclerosis endophenotype”, multiple sclerosis relatedneurodegeneration, multiple sclerosis biomarker discovery, multiple sclerosis clinical outcomes andimmune tolerance strategies. Gavin’s team focus on translational research and therefore have an activeclinical trial programme.Ian Galea is Clinical Lecturer in Neurology at the University of Southampton. He has a research interestin neuroimmunology, including the role of systemic infections in disease progression in multiple sclerosis.Ruth Dobson is currently a Clinical Research Fellow at the Blizard Institute, and an Honorary SpecialistRegistrar in Neurology at the Royal London Hospital. She currently holds an ABN/MS Society ClinicalResearch Training Fellowship, having previously been awarded a Brain Entry Scholarship by theGuarantors of Brain. Ruth has a national training number (NTN) in Neurology, and has completed 2years of clinical higher specialist training in Neurology. Her research centres around the identification ofpredictive factors in early stage MS, and working towards the determination of a pre-symptomatic stagein MS, in order to enable the identification of an “at risk” population. Ruth is doing this through studyingthe siblings of people with MS, who themselves have not developed MS. Her hope is that this work willenable large scale preventative studies in the future.MS_FrontiersHandbook_2013v2withSash.indd 10 25/04/2013 11:24
  11. 11. 11BiographiesRobyn Lucas is a medically trained epidemiologist and public health physician. After working in clinicalmedicine in New Zealand, Canada, the Solomon Islands and Australia, Robyn completed a PhD in2005, examining the effect of environmental stressors and social conditions on immune function. Shewas the study coordinator for the Ausimmune Study, examining environmental risk factors for a firstdemyelization event, in Australian adults. She was published widely on vitamin D in relation to MS andfirst demyelinating events, and has additional interests in delineating the possible separate, independentbeneficial effects of sun exposure and vitamin D status in multiple sclerosis. Robyn is an investigatoron the AusLong study examining environmental risk factors for disease progression in MS, and also thePrev/ANZ Study, a clinical trial of vitamin D supplementation to prevent MS.Lorna Paul is a physiotherapist and Reader in Rehabilitation at the University of Glasgow. Lorna hasbeen involved in MS research for over 12 years and is particularly interested in the effect of exercise forpeople with MS. Lorna was a member of the MS Society Grant Review Panel 2 for a number of years.Helen Dawes, Elizabeth Casson Trust Chair, leads the Movement Science Group based in the Facultyof Health and Life Sciences at Oxford Brookes University. Helen initially trained and practiced as aphysiotherapist specializing in sport physiotherapy and working in the UK and New Zealand, prior toundertaking postgraduate training in exercise science and neuroscience. Helen then embarked on a PhDexploring exercise for people with neurological conditions. She has since then focused on optimizingperformance of everyday activities through rehabilitation and on enabling physically active lifestylesin adults and children with disorders affecting movement such as: stroke, Parkinson’s, cerebral palsyand multiple sclerosis. Her research requires cross-disciplinary collaborations. In order to ensure thatthe research addresses important issues affecting people’s lives, all research activities are guided andmonitored by User Steering Groups (adult and children). Her activities include research, teaching and theprovision of a Clinical Exercise and Rehabilitation in the community. Her research spans from exploringunderlying mechanisms affecting performance through to service delivery of subsequently developedinterventions and tools.Mathias Mäurer, MHBA, Professor of Neurology, Senior Neurologist1987 - 1994 Medical school, Würzburg, Baltimore1994 - 1999 Training in Neurology, Department of Neurology, University of Würzburg1999 - 2001 Post-doc-fellowship, Developmental Neurobiology, University of Würzburg2001 - 2006 Research group leader clinical immunology, Clinical research unit for multiple sclerosisand neuroimmunology, University of Würzburg2004 - 2006 senior (staff) neurologist, Department of Neurology, University of Würzburg2006 - 2008 Head of the Clinical Research Group for Multiple Sclerosis and Neuroimmunology,Department of Neurology, University of Erlangen-Nurembergsince 2008 Chairman Department of Neurology Caritas Krankenhaus Bad Mergentheim Academic Teaching Hospital University of WürzrburgUlrik Dalgas, PhD is an exercise physiologist specialized in MS rehabilitation. In particular most of hisresearch focuses on the effects of exercise therapy in subjects with MS. His research covers the effectsof different exercise modalities (e.g. resistance training and endurance training) and aspects of exercisetherapy related to selected groups of MS patients (e.g. thermo-sensitive patients). The main focus is onmuscle function. His newest studies have shown that the neural drive increases, following progressiveresistance training in MS patients. Currently, he holds a position as board member in RIMS (Rehabilitationin Multiple Sclerosis) and is involved in studies conducted in the RIMS association. Here he is part of theMS_FrontiersHandbook_2013v2withSash.indd 11 25/04/2013 11:24
  12. 12. 12Biographiessteering committee of two large multicenter studies focusing on gait function in MS patients. Furthermore,he is the principal investigator of a Nordic exercise therapy study. Finally, he has contributed to the newlyrevised Recommendations on Rehabilitation Services for Persons with Multiple Sclerosis in Europepublished by the European Multiple Sclerosis Platform (EMSP).Raj Kapoor is a Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, andReader in Neurology at University College London. He graduated from the University of Oxford in 1981 andcompleted his postgraduate medical training in London. His initial research, at New York University MedicalCenter and in the University Laboratory of Physiology in Oxford, was on the basic electrophysiology ofneurones in the cerebellum and substantia nigra. He completed his neurological training at UniversityCollege London Hospitals and at the National Hospital, where he took up his present post in 1994. Hismain research interests are in the pathophysiology and treatment of demyelinating diseases. His work withProf Kenneth Smith on axonal injury in MS suggested possible ways of achieving neuroprotection andpreventing disability, which he translated into clinical trials of neuroprotection with lamotrigine in secondaryprogressive MS, and with phenytoin in optic neuritis. He is also involved in work with Prof David Miller onimaging techniques to investigate metabolic failure of the brain in MS, and in the International ProgressiveMS Consortium, which aims to expedite the development of therapies for progressive disease.Nikos Evangelou is Clinical Associate Professor of Neurology at the University of Nottingham. His clinicaltraining took place in Thessaloniki- Greece, Bristol, Oxford and Nottingham. He was awarded his DPhilin Oxford for his research in axonal loss in multiple sclerosis and he continues to be research active in thesame field. Currently his research team focuses in neuropathology and imaging in MS. He is a member ofthe MS team in Nottingham with clinical responsibility for 2500 patients with MS in the East Midlands.Richard A. Rudick, M.D.Professor of Medicine, Cleveland Clinic Lerner College of MedicineHazel Prior Hostetler Chair of Neurology, Cleveland ClinicDirector, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. Vice Chairman,Research and Development in the Neurological Institute, Cleveland Clinic; oversees developmentefforts for the Neurological Institute and for strategic planning and oversight of research programs inthe neurosciences. Dr. Rudick is co-investigator for the Case / Cleveland Clinic CTSC (Clinical andTranslational Sciences Collaborative). The CTSC is an NIH supported grant to fund education and trainingof clinical investigators, and to fund infrastructure for clinical research across the city. Dr. Rudick directsthe education and training component of the CTSC.David Miller is Professor of Clinical Neurology at the Institute of Neurology, University CollegeLondon and a Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, UCLH,London. His major clinical activities and research interests are based on multiple sclerosis. He leadsa multidisciplinary research group using magnetic resonance methods to improve diagnosis, identifyprognostic markers, understand disease mechanisms and monitor new treatments in MS. His researchhas been principally supported by the MS Society of Great Britain and Northern Ireland; a new highfield MRI scanner was installed at UCL Institute of Neurology in autumn 2009 to continue this work. Hehas published extensively in peer reviewed medical literature. He previously served as Secretary of theAssociation of British Neurologists and International Society of Magnetic Resonance in Medicine andas Co-Chief Editor of the Journal of Neurology. He has been a recipient of the Sobek Prize (2005) andDystel Prize (2009) for MS research, and is a Senior Investigator of the NHS National Institute for HealthResearch, Fellow of the Academy of Medical Sciences and Honorary Professor in the Department ofMedicine, University of Otago, Christchurch, New Zealand.MS_FrontiersHandbook_2013v2withSash.indd 12 25/04/2013 11:24
  13. 13. 13BiographiesRoger Baker has worked in a dual role as researcher and clinical psychologist at Leeds, Aberdeen Bournemouth Universities and in NHS Trusts specialising in Mental Health. He is Professor of ClinicalPsychology at Bournemouth University and Consultant Clinical Psychologist with Dorset HealthCare NHSUniversity Foundation Trust and is Chair of the MS Society’s Care and Services Grant Review Panel.He has specialised in the development of new emotion based therapies and assessments summarisedin 3 books, ‘Understanding Panic Attacks and Overcoming Fear’, ‘Emotional Processing; healing throughfeeling’ and his latest book, ‘Understanding Trauma; how to overcome post traumatic stress’.Rona Moss-Morris is Professor of Psychology as Applied to Medicine. She is head of the HealthPsychology Section at the renowned Institute of Psychiatry, King’s College London. She is also a NationalAdvisor to the Department of Health in England, for Increasing Access to Psychological Therapies forPeople with Long Term and Medically Unexplained conditions and represents the British PsychologicalSociety on the Clinical Advisory Board of the British Society of Gastroenterology. She has beenresearching psychological factors that affect symptom experience and coping with chronic conditions forthe past 18 years. This research has been used to design cognitive behavioural interventions, includingweb based interventions, for a range of patient groups. Randomised controlled trials to test the efficacyof these interventions form a key component of her research. Professor Moss-Morris’s work has beenpublished in leading medical and psychology journals and texts including the Lancet, BMJ, PsychologicalMedicine, and Journal of Consulting and Clinical Psychology. She was Editor-in-Chief of Psychology andHealth, the principal European health psychology journal from 2006-2010.Trudie Chalder is Professor of Cognitive Behavioural Psychotherapy at King’s College Londonand is currently President of the British Association of Cognitive and Behavioural Psychotherapists.She has worked as a clinician and a researcher in the area of medically unexplained symptoms suchas chronic fatigue syndrome and irritable bowel syndrome for about 25 years. She develops modelsfor understanding and treating these conditions and evaluates the approaches within the context ofrandomised controlled trials in primary, secondary and tertiary care. Her more recent research interestsinvolve developing cognitive and behavioural models and treatment of symptoms and disabilityassociated with chronic diseases such as Cancer, Multiple Sclerosis and Inflammatory Diseases.Richard Warner is a Nurse Consultant based at Gloucestershire Hospitals NHS Foundation Trust.Richard sits on the MS Society’s Care and Services research grant review panel and has been involvedwith the MS Society UK MS Register steering groupRosie Jones completed PhD in Neuromuscular Physiology at the Dept. Physiology, Medical Sciences,University of Birmingham in 1971 and held research fellow and lectureship posts before moving toUniversity College London and Charing Cross Hospital. Dept. of Clinical Neuroscience. Moved toUniversity of Bristol in 1992 as Sen. Research fellow and Principal Clinical Scientist and also headed upthe Bristol RD Support Unit from 2000 to 2009. Currently Hon. Sen. Research Fellow, University ofBristol and based at Frenchay Hospital and University Hospitals Bristol.Jon Marsden qualified as a physiotherapist in 1991; he undertook clinical rotations atthe United Bristol Healthcare trust and the National Hospital for Neurology and Neurosurgery inLondon. From 1999 he worked as a postdoctoral scientist and MRC fellow in the Sobell Dept for MotorNeuroscience and Movement Disorders, UCL. Since 2007 he has been Professor of Rehabilitation at theSchool of Health Professions, University of Plymouth. His main research interests are in the pathophysiologyand rehabilitation of walking and balance following peripheral and central nervous system damageMS_FrontiersHandbook_2013v2withSash.indd 13 25/04/2013 11:24
  14. 14. 14BiographiesJames Malone-Lee qualified from St. Thomas’ Hospital, London in 1975. He served with theRoyal Army Medical Corps until 1981 when he moved to University College London as a lecturer ingeriatric medicine. He was appointed senior lecturer in 1984 and promoted to a personal chair during1994. In 1996 he was appointed to the Barlow Chair of Geriatric Medicine. In 1999 he was posted tothe Whittington Campus of UCL Medical School as Professor of Medicine for that site. During thirtyyears he has worked as a clinical scientist focusing on common lower urinary tract symptoms, theirpathophysiology, diagnosis and treatment. In that time he has maintained a keen interest in MS.Charles ffrench-Constant graduated MA MB, BChir in Medicine from Cambridge in 1980, gainingMRCP in 1984 following posts at the Hammersmith at UCH. He then joined Martin Raff’s lab at UCL as aPhD student, followed by postdocs at MIT with Richard Hynes and Cambridge with Chris Wyllie. He was aJunior Group Leader position in the Wellcome/CRC (now Gurdon) Institute at Cambridge from 1991-1996,becoming a University Lecturer/Consultant at Addenbrookes Hospital, Cambridge from 1996 and Chair inNeurological Genetics at Cambridge from 1999. During this time, he was funded by Wellcome Trust Seniorand Research Leave Fellowships. He took his present appointment as Chair of Medical Neurology and co-director of the MS Centre at the University of Edinburgh in 2007, becoming Director of the MRC Centre forRegenerative Medicine in 2011 and Director of Edinburgh Neuroscience in 2013. His research focuses onthe biology of myelin formation and repair in the brain with the aim of discovering novel therapies in multiplesclerosis based on the activation and recruitment of endogenous stem and precursor cells.David Ford leads the MS Society funded UK MS Register project. He is also Director of the eHealthIndustries Innovation (ehi2) Centre, developing links between academia, the NHS, and business within theUK and internationally. He is University Director of the Health Informatics Research Laboratories, createdthrough a collaboration between the College of Medicine, Swansea University and NHS Wales InformaticsService, the national programme for NHS IT for Wales. The Labs provide state-of-the-art facilities todesign, prototype, test and evaluate innovative new information technologies for use in improving healthand healthcare. David is also joint lead of the Health Information Research Unit for Wales (HIRU), whichdevelops new ways of harnessing the potential of routinely collected information collected in health andother settings. HIRU’s main product is the SAIL Databank, an internationally recognised data linkageresource formed from a wide variety of routinely collected data from across Wales.David is Deputy Director of a new UK Centre of Excellence for E-Health Research (E-HIRC), funded by aconsortium of top UK research funders led by the MRC.David is a Fellow of the Royal Society for the Encouragement of the Arts, Manufactures and Commerce(FRSA) and past Chairman and a current Director of MediWales, a membership organisation representingthe medical technology sector of Wales. David is a member of numerous committees and nationalbodies relating to health informatics and health-related research. He has received research grants andconsultancy contracts valuing over 35m over recent years.Richard Reynolds studied Pharmacology at King’s College London from 1975 to 1981 beforeembarking on a career in MS research and has now been Professor of Cellular Neuroscience at ImperialCollege, London, for the last 13 years. He is the Scientific Director of the Multiple Sclerosis SocietyTissue Bank and also heads an MS research unit in the Division of Brain Sciences on the HammersmithHospital campus. Professor Reynolds has been carrying out MS related research for the last 26 yearsand current research in the unit is designed to gain an understanding of the mechanisms involved in bothneurodegeneration and repair processes in the brain in MS. This research is dependent on a supply ofwell characterised human brain tissue that has been collected by the MS Tissue Bank because of thedesire of the MS community to contribute to the research in a practical way. This work has led him to beinvolved in teaching both science and medical students about MS and to travel around the British Isleshelping people with the illness understand what is happening to them.MS_FrontiersHandbook_2013v2withSash.indd 14 25/04/2013 11:24
  15. 15. 15BiographiesHans Lassmann graduated from Medical School at the University of Vienna in 1975. He thenjoined the Institute of Neurology of the University of Vienna for training in clinical and experimentalneuropathology. In addition he spent one year as a post doc at the Institute for Basic Research inDevelopmental Disabilities in New York. In 1990 he became director of the Research Unit for ExperimentalNeuropathology of the Austrian Academy of Science and in 1993 Professor for ExperimentalNeuropathology in the University of Vienna. From 1999 to 2007 he was the founding director of theCenter for Brain Research of the Medical University of Vienna. He is member of the Austrian Academy ofSciences and the Deutsche Akademie der Naturforscher Leopoldina. In 2005 he received the CharcotAward of the Multiple Sclerosis International FederationMS_FrontiersHandbook_2013v2withSash.indd 15 25/04/2013 11:24
  16. 16. 16Presentation abstractsThursday 9 MayPlenary sessionInflammation and axonal damage: protective vs detrimental mechanismsZipp, Frauke, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2),University Medical Center Mainz, Department of Neurology, frauke.zipp@unimedizin-mainz.deLatest developments in Genetics indicate that Multiple Sclerosis (MS) is truly a primarily inflammatory disease.Distinct conditions of immune responses in the target organ traditionally referred to as the brain’s ‘immune privilege’make MS a peculiar and specific disease. Findings in patients are a complex amalgam of inflammation - typicallyin subcortical, but also cortical disseminated lesions - and early injury of the neuronal compartment as well asneurodegeneration.Our data show a crucial and unique role of dendritic cells – which are suggested to be of importance in themechanism of action of several novel therapeutic strategies - for the initial step of invasion and then survival of IL-17-producing Th17 cells within the target organ. Adhesion of T cells to neurons plays an important role as first stepin the damaging cascade within the central nervous system (CNS) on the one hand, but endogenous repair occurswithin the CNS despite an ongoing inflammatory attack on the other hand. Obviously, remissions of clinical relapsespoint to repair capacities of the CNS and/or the immune system, resulting in strong inter-individual and course-dependent differences.Considering MS as both inflammatory and neurodegenerative has major implications for therapy, with CNS protectionand repair needed in addition to controlling inflammation.Pragmatic Exercise Intervention for People with MS: the ExIMS trialJohn SaxtonUniversity of East AngliaExercise is an effective intervention for improving function, mobility and health-related quality of life in peoplewith multiple sclerosis (PwMS). Questions remain however, regarding the effectiveness of pragmatic exerciseinterventions for evoking tangible and sustained increases in physical activity and long-term impact on importanthealth outcomes in PwMS. These issues, and improved knowledge of cost effectiveness, are likely to influencekey decisions of health policy makers regarding the implementation of exercise therapy as part of the patient carepathway for PwMS. Hence, the primary aim of this study was to investigate whether a 12-week tapered programmeof supervised exercise, incorporating cognitive-behavioural techniques to facilitate sustained behaviour change,was effective for evoking improvements in physical activity and key health outcomes in PwMS over 9 months offollow-up. PwMS were randomised to the pragmatic exercise therapy intervention or usual care control group. Theintervention increased physical activity levels and resulted in significant improvements in fatigue and quality of life.This presentation will report the main results of the trial and consider implications for future research.MS_FrontiersHandbook_2013v2withSash.indd 16 25/04/2013 11:24
  17. 17. 17Presentation abstractsParallel sessionsA: Mechanisms of axonal damageHugh PerryUniversity of SouthamptonInjury to axons and the accompanying Wallerian degeneration is a major component of the pathology of multiplesclerosis. Axon injury and the subsequent degeneration is and irreversible lesion and believed to underlie diseaseprogression. In this symposium speakers will present recent findings on the molecular events that underpin axondegeneration and the response of the innate immune cells of the CNS.Mitochondrial changes in neuronal soma and demyelinated axonin multiple sclerosis: implications for axon pathology.Don MahadCentre for Neuroregeneration, Chancellor’s Building, University of EdinburghMitochondrial abnormalities are now established in MS. Mitochondrial dysfunction resulting from respiratory chainenzyme deficiency is a consistent feature of most cortical motor neurons and approximately one third of dorsalroot ganglia neurons in progressive MS. The demyelinated axons, however, showed an increase in mitochondrialdensity, activity and motility. Subsequent studies indicate this axonal mitochondrial response to demyelination asa homeostatic phenomenon. Neuropathological examination of a number of established models of MS has notshown the type of mitochondrial abnormalities evident within neuronal soma in MS. Here, I discuss the mitochondrialchanges observed within neurons in progressive MS, their implications for axon pathology in progressive MS andlimitations of the existing models in recapitulating these mitochondrial changes evident within neuronal soma in MS.Mechanisms of axon degenerationColeman, M. P., Gilley, J., Milde, S., Di Stefano, M., Nascimento-Ferreira, I., Orsomando, G. and Conforti, L.The Babraham InstituteStructure-function studies of the slow Wallerian degeneration protein and related Nmnat isoforms indicate thatNmnat activity within axons is critical for axon survival. Of the three mammalian isoforms, only Nmnat2 has beenconfirmed to be an endogenous axonal protein. As it is a labile protein, axons are vulnerable to interruptions inanterograde delivery of Nmnat2 such as that likely to occur in multiple sclerosis. Experimental nerve injury, orknockdown or knockout of Nmnat2 can be used to model this interruption in supply. Thus, axons in primary cultureundergo Wallerian-like degeneration when Nmnat2 is knocked down, and peripheral nerve growth fails withoutNmnat2.While Nmnat2 is delivered to axons on membrane-bound transport vesicles, we find that this is not its main site ofaction. Its limited protective capacity for injured axons is greatly enhanced by dissociation from these vesicles to alevel similar to WldS, suggesting a cytosolic site of action. Intriguingly, Nampt, another protein that we find to be acritical determinant of axon survival, is also cytosolic. This proximity may be important for Nmnat2 to sequester theNampt product, NMN, which accumulates in injured and explanted nerves and induces axon degeneration unlessan enzyme activity is present to remove it. Thus, Nampt inhibition phenocopies WldS. The pathway relationshipwith other emerging regulators of axon survival such as Sarm1 will be the key to identifying the most promisingtherapeutic targets for disorders of anterograde axonal transport.MS_FrontiersHandbook_2013v2withSash.indd 17 25/04/2013 11:24
  18. 18. 18Presentation abstractsThe Immune System in Neurodegenerative DiseasesSandra AmorVU University Medical CenterNeurodegeneration, the slow and progressive dysfunction and loss of neurons and axons in the central nervoussystem, is the primary pathological feature of acute and chronic neurodegenerative conditions. Neurodegenerationis also observed in many diseases including neurotropic viral infections, stroke, paraneoplastic disorders,traumatic brain injury, and multiple sclerosis. Despite the many different triggering events, a common feature ofneurodegenerative diseases is chronic immune activation, in particular of microglia, the resident macrophages of thecentral nervous system.Apart from the pathogenic role of both innate and adaptive immune responses in neurodegenerative diseases,emerging evidence indicates that those immune responses are also critical for neuroregeneration. I will reviewthe impact of immune responses on the CNS, and discuss their contribution to either damage or repair. Abetter understanding of the interaction between the immune and nervous systems will be crucial to either targetpathogenic responses, or augment the beneficial effects of immune responses as a strategy to intervene in chronicneurodegenerative diseases.B: Risk factors of MSSystemic infections and disease progressionIan GaleaClinical Neurosciences, Faculty of Medicine, University of SouthamptonThe relationship between systemic infections and progression of disability in multiple sclerosis is complex. Plentyof evidence suggests that systemic infections precipitate relapses, and that lack of recovery from relapses maycontribute to progression, but the link between the two is tenuous. Systemic infections may also contributedirectly to the process of neurodegeneration, separate from relapses. The evidence for and against this concept,from our group and others, will be presented. Dissecting the relationship between systemic infections and diseaseprogression is helping us understand the progressive phase, which is a priority.MS_FrontiersHandbook_2013v2withSash.indd 18 25/04/2013 11:24
  19. 19. 19Presentation abstractsThe MS endophenotype: vitamin D, EBV and genesDr Ruth DobsonBarts and the London School of MedicineObjective: An endophenotype is a concept that allows us to describe complex diseases with genetic andenvironmental contributions. This enables the identification of an “at risk” population. We aim to describe anendophenotypic gradient between healthy controls (HC), siblings of people with MS (PwMS) and PwMS.Background: Siblings of PwMS have an increased risk of developing MS. This increased risk is thought to be aresult of genetic and environmental contributions. Epidemiological studies have identified factors contributing toMS including smoking, vitamin-D, infection with and IgG titres against Epstein-Barr virus and HLA-DRB1*1501. Agenome wide association study (GWAS) in 2011 gave information regarding the contribution of HLA-type and non-HLA SNPs to MS risk. We set out to integrate these into an endophenotypic risk score for MS.Methods: PwMS (n=78), their unaffected siblings (n=121) and healthy controls (HC; n=103) were recruited. Serumanti-EBNA-1 IgG, vitamin D and cotinine were measured. Subjects were genotyped for HLA-DRB1*1501 and allHLA and non-HLA SNPs associated with MS using the Illumina immunochip. Previous infectious mononucleosis,smoking and month of birth were recorded. The relative risks associated with these factors were established frommeta-analyses and integrated into an overall risk score for each individual. Full genetic data was available for 73people with MS, 107 siblings and 99 HC.Results: When the genetic contribution from HLA-DRB1*1501 alone was used, the mean risk score wassignificantly higher for PwMS than for siblings or HC. Siblings had a risk score higher than HC. The differencesbetween the three groups became more apparent when all genetic information was integrated into the risk score.Conclusions: This study demonstrates the validity of the risk score generated, which integrates genetic andenvironmental risk factors. Siblings have a risk score intermediate to PwMS and HC, confirming their “at risk”position in the endophenotype construct. Much of the MS risk in siblings can be attributed to genetics, withenvironmental factors potentially providing the trigger for clinically apparent disease.MS_FrontiersHandbook_2013v2withSash.indd 19 25/04/2013 11:24
  20. 20. 20Presentation abstractsVitamin D, (sun exposure) and Multiple SclerosisRobyn M Lucas, National Centre for Epidemiology and Population Health, The Australian National University,Canberra, AustraliaGeographic variation in the occurrence of multiple sclerosis (MS), first reported in the academic literature in 19221,and evidence from a number of epidemiological studies, suggest that MS is more common in populations living inregions where levels of ultraviolet radiation (UVR, from the sun) are low (for example at high latitudes)2 3, in peoplehaving low levels of sun exposure4 5, or with low vitamin D intake6or vitamin D levels in blood7. Observations of acorrelation between MS and latitude or UVR levels suggest a link, but could also be explained by other factors thatvary by latitude – such as temperature, patterns of infection, diet and possibly genetic susceptibility (due to migrationpatterns). Individual-level studies first examined sun exposure/vitamin D in people with MS, where it is difficult todetermine whether low sun exposure/vitamin D caused the MS, or MS caused the low sun exposure/vitamin D,i.e. people with MS spend less time outside because of heat intolerance or disability. Stronger evidence came fromlongitudinal studies where low vitamin D intake from supplements or low vitamin D levels in blood were associatedwith increased risk of developing MS. But the intake data rely on participant’s recalling their diet and supplementuse, and an assumption about the vitamin D content of the supplements. Low vitamin D levels in blood providestronger evidence, but are unable to distinguish between the effects of sun exposure and those of vitamin D itself.The Ausimmune Study was conducted in Australia from 2003-2008 to examine the effects of sun exposure, vitaminD, other environmental factors and genetic factors on the risk of developing MS. Australia has a wide latitudinalspan and widely varying UVR levels – and it is warm in the north and cold in the south, so there is wide variationin the amount of sun exposure people have, and their vitamin D levels. We recruited 282 people with a first clinicaldiagnosis of CNS demyelination and 558 age and sex matched controls from the general population. There was alatitude gradient in occurrence – a four-fold increase from the lowest latitude to the highest latitude regions8. Peoplewith newly diagnosed disease reported lower sun exposure over their lifetimes and had lower vitamin D levels thantheir matched population controls. Sun exposure was related to vitamin D levels, but lower levels of sun exposureand lower vitamin D levels were both (independently) important for increased disease risk9.What are the implications for prevention trials? The evidence suggests that maintaining higher vitamin D levelscould reduce the risk of developing MS. If low vitamin D and low sun exposure are independent risk factors for MS,then vitamin D supplementation will provide a benefit, but not the full benefit of higher vitamin D levels (since thesereflect both sun exposure and vitamin D intake). Prevention trials with vitamin D supplementation are now requiredto establish whether this intervention is able to decrease the risk of developing MS. Outstanding questions include:1). When is the supplementation required? Is it in the period leading up to the diagnosis, over the whole of thelifecourse, in utero, childhood? 2). Where is the best place to do such a study? In Australia, with high ambient UVRlevels, vitamin D levels in blood will reflect not only supplementation but sun exposure. To best understand the valueof vitamin D supplementation, would it be better to conduct a trial in a high latitude region, where vitamin D from sunexposure is less likely to be important? 3). What will the comparison groups be, when many people who perceivethemselves at risk already take a vitamin D supplement? 4). What is the best study design, for this disease that isrelatively uncommon and may occur many years after the relevant risk exposure? In light of this, what are the fundingconsiderations? Many of these questions will be considered in discussion of the PrevANZ Study that is currentlyunderway in Australia, funded by MS Research Australia.References1. Davenport C. Multiple sclerosis from the standpoint of geographic distribution and race. Arch Neurol Psychiat1922;8(1):51.2. Acheson ED, Bachrach CA, Wright FM. Some comments on the relationship of the distribution of MultipleSclerosis to latitude, solar radiation and other variables. 1960:132-47.3. Simpson S, Jr., Blizzard L, Otahal P, Van der Mei I, Taylor B. Latitude is significantly associated with theprevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry 2011;82(10):1132-41.4. van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Simmons R, Taylor BV, et al. Past exposure to sun, skinphenotype, and risk of multiple sclerosis: case-control study. Bmj 2003;327(7410):316-21.MS_FrontiersHandbook_2013v2withSash.indd 20 25/04/2013 11:24
  21. 21. 21MS Frontiers programme5. Kampman MT, Wilsgaard T, Mellgren SI. Outdoor activities and diet in childhood and adolescence relate to MSrisk above the Arctic Circle. J Neurol 2007;254(4):471-7.6. Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ, Willett WC, et al. Vitamin D intake and incidence ofmultiple sclerosis. Neurology 2004;62(1):60-5.7. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiplesclerosis. Jama 2006;296(23):2832-8.8. Taylor BV, Lucas RM, Dear K, Kilpatrick TJ, Pender MP, van der Mei IA, et al. Latitudinal variation in incidence andtype of first central nervous system demyelinating events. Mult Scler 2010;16(4):398-405.9. Lucas RM, Ponsonby AL, Dear K, Valery PC, Pender MP, Taylor BV, et al. Sun exposure and vitamin D areindependent risk factors for CNS demyelination. Neurology 2011;76(6):540-8.C: Physical activity/exercise in MSExercise in multiple sclerosisMathias Mäurer, MDCaritas Krankenhaus Bad Mergentheim, University of Würzburg, GermanyDue to the numerous symptoms of the disease, Multiple Sclerosis (MS) patients show an even more distinct physicalinactivity than the normal population. This inactivity leads to secondary complications like adiposity, cardiovasculardiseases, muscle weakness, pain or fatigue, which all can overlay the primary symptoms of MS and reduce healthand quality of life. Thus, physical activity and exercise should be considered a prerequisite for health promotion inMS patients. There is no evidence to support the formerly assumed opinion that exercise can be harmful for MSpatients. In the contrary, the effectiveness of exercise in multiple sclerosis patients has been extensively proven,especially in the past decade. Numerous studies have shown positive effects of aerobic or strength training onsymptoms and quality of life in MS patients. Although MS patients in general are considered to be quite inactivethere is a considerable amount of physically very active patients. In a recently performed survey we could identify alarge amount of MS patients that qualify themselves as very active. To address this very interesting subgroup of MSpatients we designed an internet base training program. As shown recently using internet technology might treat andsupervise patients more economically and more individually than conventional interventions, but systematic studiesare lacking. Data of an randomized controlled trial evaluating E-training will be presented.Exercise and disease progression in MSUlrik DalgasSection for Sport Science, Dept. of Public Health, Aarhus University, DenmarkFor many years patients with multiple sclerosis (MS) were recommended to avoid physical exercise. This advicewas given because it was noted that exercise could worsen symptoms and induce fatigue. Today we know that theworsening of symptoms is a temporary phenomenon and that exercise poses the potential to reduce chronic fatigue.An even larger change of paradigm is the fact that some researchers have started to suggest that exercise (orphysical activity) might have the potential to have an impact on multiple sclerosis (MS) pathology and thereby slowdown the disease process.Recently, we conducted a systematic literature search on this topic, which showed that different methodologicalapproaches to the problem have been applied including (1) longitudinal exercise studies evaluating the effects onclinical outcome measures, (2) cross-sectional studies evaluating the relationship between fitness status and MRIfindings, (3) cross-sectional and longitudinal studies evaluating the relationship between exercise/physical activityand disability/relapse rate and, finally, (4) longitudinal exercise studies applying the experimental autoimmuneencephalomyelitis (EAE) animal model of MS. Data from intervention studies evaluating disease progression byclinical measures (1) do not support a disease-modifying effect of exercise; however, MRI data (2), patient-reporteddata (3) and data from the EAE model (4) indicate a possible disease-modifying effect of exercise, but the strengthMS_FrontiersHandbook_2013v2withSash.indd 21 25/04/2013 11:24
  22. 22. 22MS Frontiers programmeof the evidence limits definite conclusions. Taken together some evidence supports the possibility of a disease-modifying potential of exercise (or physical activity) in MS patients, but future studies using better methodologies areneeded to confirm this.Symptoms of fatigue following high intensity exercise inpeople with Multiple SclerosisHelen DawesOxford Brookes UniversityThe session will explore the exercise response and recovery during and following a single high intensity (maximum)exercise session in people with Multiple Sclerosis (PwMS). PwMS benefit their mobility and function fromparticipation in high intensity exercise but some individuals tolerate this intensity less well than lower intensityexercise. We explore recovery of symptoms of leg fatigue following high intensity exercise in relation to physiologicalmeasures.55 PwMS and 15 healthy, low active controls performed incremental exercise to voluntary exhaustion. Physiologicalmeasures (expired air and heart rate), perceived breathlessness, and leg fatigue symptoms were measured duringand for ten minutes following exercise. Measures of baseline disability, activity, vitality and fatigue were recorded.PwMS had a reduced exercise capacity but normal exercise response. PwMS reporting fatigue as an everydaysymptom exhibited reduced exercise capacity, but a normal exercise response compared to their non-fatiguedpeers. Physiological markers and breathlessness recovered at the same rate in all groups. However whenconsidering symptoms experienced from exercise, symptoms of leg fatigue had recovered less at ten minutesfollowing exercise in PwMS compared to the control group and particularly in those reporting fatigue as an everydaysymptom.We propose that PwMS have a normal physiological exercise response but that symptoms of leg fatigue afterintense exercise may require longer than expected to recover, particularly in individuals with higher baseline levelsof general fatigue. Leg fatigue symptoms monitored during recovery from physical activities may provide a sensitivemarker to guide appropriate physical activity in PwMS particularly in those managing high levels of general fatigue.DebateThere is compelling evidence that early aggressive treatment ofMS leads to long-term benefits for the patient and this should beconsidered the ‘norm’ in clinical practiceChair: Raj Kapoor, National Institute of Neurology and Neursurgery, Queen Square, LondonFor the motion: Gavin Giovannoni, Barts and the London NHS TrustAgainst the motion: Nikos Evangelou, Queens Medical Centre, Nottingham Hospitals NHS TrustThere is currently widespread debate about whether early aggressive treatment of MS is better for the patient inthe long-term. This debate will focus on the evidence behind early aggressive treatment of MS and review thearguments for and against. Delegates will be asked to vote on the motion before and after the debate. Argumentswill address the following questions:• Does early aggressive treatment have an impact on disability progression?• How should benefits and risks be weighed up and what can/needs to be done in order to help peopleaffected by MS make more informed decisions on treatment risks and benefits?• Should there be first and second line treatments or should each patient be assessed individually?• Are criteria for assessing treatment failure appropriate?MS_FrontiersHandbook_2013v2withSash.indd 22 25/04/2013 11:24
  23. 23. 23Presentation abstractsFriday 10 MayParallel sessionsA: Biomarkers and clinical outcome measures:challenges for progressive MS trialsThe Multiple Sclerosis Outcome Assessments Consortium: AcceleratingDevelopment of Treatments for Multiple SclerosisRudick, R. (Cleveland, OH, USA); LaRocca, N. (NY, NY, USA), and Hudson, L.D. (Tucson, AZ, USA)Successful development of disease-modifying drugs for relapsing forms of MS is a landmark achievement inneurotherapeutics. Despite that progress, however, treatments that slow or halt disability progression by inhibitingneural degeneration or promoting regeneration are lacking, representing a significant unmet medical need.Trial designs that proved effective for new MRI lesions and relapses may not be optimal for detecting disabilityprogression. New designs that incorporate validated outcome measures focused on disability will be required.The US FDA has established a pathway to qualify biomarkers, patient-reported outcomes, and clinician-reportedoutcomes (ClinROs). With that in mind, the National Multiple Sclerosis Society (NMSS) has entered into a partnershipwith the Critical Path Institute to create a new Multiple Sclerosis Outcome Assessments Consortium (MSOAC). TheMSOAC is a coalition of industry, academia, patient representatives, regulatory and other government agencies, andthe NMSS. To achieve its goal, the MSOAC will create a database of clinical trial and observational study datasets,analyze these, and develop evidence leading to qualification of a new ClinRO measure of disability by FDA and EMA.Participating companies, academic investigators, advocacy organizations, and regulatory agencies will be listed.We will describe the project’s close collaboration with the FDA and EMA, and present details of the project plan.The MSOAC represents a new paradigm in multidisciplinary, collaborative research in which all sectors of the drugdevelopment enterprise cooperate in an effort to accelerate progress in developing treatments for progressive formsof MS. The consortium will be well-positioned for additional collaborative projects aimed at accelerating developmentof more effective treatments for MS.Imaging outcome measures: challenge for MS trialsDavid Miller, National Institute of Neurology and NeurosurgeryImaging techniques are a direct means of monitoring the pathology of multiple sclerosis (MS) in life. Because muchof the pathology is clinically silent, imaging offers a sensitive outcome measure in MS clinical trials. However, to bea reliable surrogate measure, it should also reflect and predict a clinically meaningful outcome such as relapse rateand development of disability. In relapsing remitting MS, new and gadolinium enhancing lesions are well establishedas a surrogate outcome measure for relapses, as shown in multiple clinical trials. In progressive MS, the focus ison imaging neurodegeneration and repair. Promising outcome measures are emerging, particularly brain atrophy,which is the primary outcome measure in proof of concept trials of several experimental neuroprotective agents inprogressive MS. Lesion MTR is an outcome measure in several trials of experimental remyelinating therapies. Theseand other emerging imaging markers of neuro-protection and repair will be discussed.MS_FrontiersHandbook_2013v2withSash.indd 23 25/04/2013 11:24
  24. 24. 24Presentation abstractsB. The psychological impact of MS and therole of psychological interventionsUnderstanding adjustment to Multiple sclerosis: How can we help?Rona Moss Morris, King’s College LondonMultiple Sclerosis (MS) poses significant challenges for adjustment. It tends to be diagnosed at a time of lifewhen people are most productive. The disease imposes a lifetime of uncertainly and the possibility of increasingsymptoms and disability. In this paper I will present a model of adjustment to MS which we developed from asystematic review of 72 published studies and qualitative interviews with 30 people with MS diagnosed within thepast 10 years and 15 of their spouses.I will discuss factors which have been shown to be related to good adjustment such as seeking social support,acceptance of the illness, positively reinterpreting situations, good health behaviours and a sense of control over theillness. I will also consider factors which are related to worse adjustment in MS, such as high levels of perceivedstress, perceiving MS and symptoms as threatening, and avoidance coping strategies. I will show how we haveused this information to design a cognitive behavioural therapy (CBT) programme to assist adjustment to MS.This CBT package was shown in a recent randomised controlled trial to be significantly more effective at reducingdistress in early stage MS than supportive listening. Finally – I will discuss new directions for this work based onquantitative and qualitative analyses of the RCT findings.C. Innovations in symptom management, care and supportUnraveling tremor: difficulties of quantifying a complex disabling symptom inMS and the development of a clinical tremor measurement workstationAuthors: Rosie Jones, Angela Davies Smith, North Bristol NHS TrustDavid Western, Simon Neild, Rick Hyde, University of Bristol.Tremor is often part of a complex upper limb movement disorder experienced by between 30-50% of people withMS. It may vary from a mild intention tremor to large amplitude more random movements making everyday tasksdifficult or impossible resulting in a high level of dependence on others. Currently there is no fully effective treatmentfor this problem.Lengthy clinical scales used to fully assess upper limb movement, while useful in research, are time consumingand challenging to the patient. They provide little information on the characterization of the movement disorder, areprone to ceiling or floor effects and are rarely used in routine neurological practice. We aim to develop a clinicalworkstation able to quantify tremor and provide detailed information about the nature of the movement disorder. Thesystem to be demonstrated records upper limb movements using five small 3D sensors attached over the sternum,shoulder, upper arm, lower arm, and hand. The sensors record the orientation of each body segment at eachpoint in time. These data are combined with a simple model of the patient’s body geometry to reconstruct theirmovements for review and analysis.The workstation software allows the clinician to apply further processing to the recordings to distinguish tremorfrom underlying purposeful movements or abnormal movements and to quickly extract objective information aboutthe occurrence of tremor and other movement characteristics such as amplitude and frequency. Measurementsmay then be correlated with conventional clinical assessments of tremor, while also offering greater detail andspecificity. The calculations can be focused on the movement at the hand, but it is also possible to examine theactivity in individual joints and to define their separate contributions to hand movement. These capabilities will bedemonstrated during the workshop, and discussed in terms of their potential for the characterization, monitoring,and treatment of movement disorders.MS_FrontiersHandbook_2013v2withSash.indd 24 25/04/2013 11:24
  25. 25. 25Presentation abstractsThe study is a work in progress and comments regarding the output and validation of the system are welcome. Avalid and reliable measure of upper limb movement dysfunction is needed if new strategies to treat this disablingsymptom in MS are to be developed and fully evaluated. The proposed clinical measurement system aims to deliverrapid, user friendly, quantifiable information during full range movement representing normal everyday tasks.This abstract summarizes independent research funded by the National Institute for Health Research (NIHR) underthe i4i (Invention for Innovation) programme (Grant Reference Number II-AR-0410-12030). The views expressed arethose of the author(s) and not necessarily those of the NHS, the NIHR or the Department of HealthAssessing and Suppressing Tremor to enable Independence:Development of a Clinical Workstation.Rosie Jones, Angela Davies Smith, Simon Neild, David Western, Richard HydeUniversity Hospitals NHS Foundation Trust and North Bristol NHS TrustIntroduction: Between 30-50% of people with MS reportedly experience tremor. In MS this can be a particularlycomplex movement disorder presenting as intention tremor and often accompanied by upper limb weakness, fatigueand gross ataxic movements. Currently there is no effective treatment. The impact on daily activities often results ina high degree of dependence. Routinely used clinical scales to assess upper limb tremor are useful but offer littledetailed information about the nature of the movement disorder.One aim of this project is to develop a user-friendly, standalone clinical workstation with bespoke software enablingrecording and analysis of upper limb movements. The recording system comprises five 3D body worn sensors(Xsens) recording standardised movements and functional tasks. Sections of recorded stored data can be selectedfor more detailed analysis alongside clinical assessment. Data generated by the workstation are used to providequantitative analysis of type and severity of movement disorder, evaluation of treatment, and exploring the means ofdefining suitability for neurosurgical intervention. The project is in progress and this abstract will concentrate on thedevelopment of the clinical workstation.Methodology: People with MS displaying various levels of abnormal upper limb movement and tremor are beingrecruited from the BrAMS Clinical Centre at Frenchay Hospital, Bristol. Each subject undergoes clinical assessment(Fahn Scale, Multidimensional Assessment of Tremor in MS, Brief Ataxia Rating Scale) and completes questionnaires(MSIS-29, EQ-5D-5L) to evaluate tremor and its impact. The sensors are attached over sternum, shoulder, proximal toelbow and wrist and dorsal surface of the hand. Recordings of a series of standardised movement tasks are made andthe data transmitted by wireless link to the workstation computer. Simultaneous video recordings are made.Stored data and video can be played back for further analysis, subject feedback, quantitative tracking of symptomsand further refinement of the workstation analysis programmes. Clinician and subject feedback is being used toinform development of the workstation and its output.Results: To date bilateral recordings have been completed with seven people with MS and three control subjects.The standalone system provides real time data on tremor frequency, amplitude, origin and occurrence duringdifferent phases of movement. Sample data derived from the recordings will illustrate:1. Characterisation of movement disorder and severity2. Development of workstation software and data presentation3. Evaluation of treatment strategiesTo date, recorded tremor amplitude has been shown to correlate with clinical tremor assessment and the occurrenceof tremor can be distinguished from larger amplitude intentional or non-intentional movements.Summary: The development of the workstation enables the collection of real time quantitative data on upper limbmovement that can be carried out in a clinical setting, and stored for immediate and on-going comparative studies.Simultaneous video recording provides visual record of movement for comparison with the clinical assessments. Theworkstation will be demonstrated.MS_FrontiersHandbook_2013v2withSash.indd 25 25/04/2013 11:24
  26. 26. 26Presentation abstractsThis abstract summarises independent research funded by the National Institute for Health Research (NIHR) underits i4i Programme (Grant Reference Number 11-AR-0410-12030). The views expressed are those of the author(s)and not necessarily those of the NHS, the NIHR or the Department of Health.Effect of Stretching on Stiffness and Range of Motion inPeople with Multiple SclerosisJon MarsdenUniversity of PlymouthHypertonia is seen in up to 85% of people with Multiple Sclerosis (pwMS) resulting in disability and functionalrestrictions. Hypertonia can be caused by increases in passive stiffness and enhanced stretch reflexes (spasticity)and is frequently managed clinically using passive stretches. However, recent systematic reviews suggest thatstretching may not be effective in improving passive stiffness and spasticity in people with an Upper Motor Neuronsyndrome. However, many of the studies to date vary considerably in the parameters of stretching used and thismay influence their findings. The impact of parameters of stretching such as the type of stretch, the applied forceand the duration of stretch on range of motion, passive stiffness and spasticity will be explored in this workshop.Recent work has further highlighted that following an upper motor neuron syndrome muscle fibres can becomeshorter and stiffer whilst the in series tendon may become more compliant and longer. As most stretch paradigmsapply force to both the tendon and muscle this raises the possibility that some stretches may not greatly affect thestiffest component of the musculotendinous complex thus limiting their effectiveness.Real progress in managing the bladder in MSJames Malone-LeeUniversity College LondonBenefitting from a research grant for the MS Society we have applied recent discoveries about the diagnosis andmicrobiology of urinary infection to people suffering from MS. Much to our surprise we found an extremely highprevalence of undiagnosed urinary tract infection amongst MS sufferers with lower urinary tract symptoms. It wouldseem that in many cases the infections had been present for years. We found that people were invariably affected bymixed microbial infections which would be dismissed as contamination by most laboratories. During an observationalstudy we treated these infections with protracted antibiotic courses, sometimes using combined antimicrobials, andobserved remarkable changes in bladder symptoms, and more importantly, general system health and the impact ofMS symptoms (F=10, df=2, p.0001). We were able to reduce the use of intermittent self-cauterisation substantiallyto (12%) of patients. We obviated the use of urodynamics and other invasive investigations. These findings are nowsubject to randomised controlled trial. A key finding was that there was a marked dose-response relationship inthe therapeutic effect, which dictates high antibiotic doses. A previous MS Society sponsored study conductedhere comes to our rescue on this point. We discovered the remarkable properties of topical bladder therapeutics byadministration of drugs directly into the bladder. Hence we are now working with non-engineers in order to developnew formulations specifically for MS sufferers which will reduce invasive bladder access, for this purpose, to aminimumMS_FrontiersHandbook_2013v2withSash.indd 26 25/04/2013 11:24
  27. 27. 27Presentation abstractsPlenary SessionStrategies for target discovery to promote remyelinationCharles ffrench-Constant, University of EdinburghThe Edinburgh Centre for Translational Research was established in 2007. The remit of the Centre is the discoveryand delivery of novel approaches to progressive MS. Our initial focus has been on enhancing remyelination basedon studies of the triad of -ologies in regeneration - tissue biology, stem cell biology and inflammation biology. I willillustrate how our work, often performed in collaboration with Cambridge colleagues so as to realize the addedvalue of having two MS Society Centres, has led to the discovery of a number of novel targets for drug therapies.The Centre has also been instrumental in catalyzing a number of significant translational and clinical developmentsin Edinburgh based around regenerative medicine, and I will describe how the critical mass we have developed willenable us to extend our work addressing the problems of progressive disease.Achievements of the MS Register in the first three years and future plansDavid Ford, University of SwanseaThe MS Register Project, funded by the MS Society, is now in its second year of data collection. The project isentering an exciting new phase, having developed and implemented a successful data collection methodologyduring the pilot phase of the project. The project now aims to consolidate its work and build recruitment so thatuseful research results can be delivered from the Register’s data.The underlying tenet of the Register is to collect data from 3 sources, namely from clinical staff at specialist NHStreatment sites; from other healthcare sources; and directly from people with MS via the Internet. This Internet‘portal’ is available to all PwMS within the UK. The portal has been designed to capture a range of outcomemeasures and accompanying data about all aspects of living with MS in the UK. Users are asked to answer up to10 questionnaires and then return every 3 months to provide further information about their condition. This data isthen linked to their clinical record – initially if they live near one of the Registers 5 pilot sites and they have consentedto do so. The Register is also able to quickly deliver targeted questionnaires to any of the Portal’s registered users,making it a powerful research platform to support a wide range of future research studies. The Register portal nowhas over 10,000 users with a rapidly rising number of people consented at the clinical sites.The Register team has already published 8 articles in peer reviewed journals and aims to raise the profile of theRegister as platform to the research community involved in MS research.MS_FrontiersHandbook_2013v2withSash.indd 27 25/04/2013 11:24
  28. 28. 28Presentation abstractsIan McDonald Memorial LectureMechanisms of Tissue Injury in Multiple Sclerosis:Lessons for Understanding Progressive MSHans Lassmann (MD)Center for Brain Research, Medical University of Vienna, AustriaMultiple sclerosis is defined as an inflammatory demyelinating disease, giving riseto focal plaques of primary demyelination in the white matter. This original definitionhas been expanded during the last decade by the observation of prominent lesions,which affect the grey matter, and by the presence of diffuse tissue injury in theentire brain. Active demyelination and neurodegeneration in the MS brain occurson the background of inflammation, consisting of lymphocyte infiltrates and theactivation of macrophages and microglia. Inflammation decreases with age of thepatients and disease duration, and the inflammatory process becomes at least inpart trapped behind a closed or repaired blood brain barrier. Demyelination andneurodegeneration is associated with microglia activation. A prominent role ofoxidative injury is reflected by the appearance of oxidized proteins, lipids and DNAin degenerating oligodendrocytes, neurons and axons. In early disease stages,oxidative injury is mainly driven by inflammation and oxidative burst in microglia,which highly express components of the NADPH oxidase complex. With increasingage of the patients and disease duration additional mechanisms become apparent,which further amplify oxidative damage. These include age related accumulationof iron in the human central nervous system, as well as age, inflammation andchronic tissue injury related accumulation of mitochondrial injury and microgliaactivation. These data suggest that demyelination and neurodegeneration is drivenby inflammation at all stages of the disease, but that in the progressive stage ofthe disease the brain and spinal cord tissue becomes more susceptible to furtherinjury by additional factors, which are related to brain aging and the progressiveaccumulation per-existing damage within the central nervous system. While theinflammatory mechanisms, operating in early stages of MS, are well reflected inexperimental models of autoimmune encephalomyelitis, these models have majorlimitations for the analysis of tissue injury in the progressive stage of the disease.MS_FrontiersHandbook_2013v2withSash.indd 28 25/04/2013 11:24
  29. 29. 29Abstracts1. Autologous stem cell transplantation depletes IL-17 producing,mucosal associated invariant T cells in multiple sclerosisAbrahamsson S, D Angelini, A Dubinsky, E Morel, U Oh, J Jones, D Carassiti, R Reynolds, M Salvetti, PCalabresi, A Coles, L Battistini, R Martin, R Burt, and P MuraroImperial College LondonAutologous haematopoietic stem cell transplantation has been tried as an experimental strategy for the treatment ofpatients with aggressive multiple sclerosis who do not respond to other immunotherapies. The procedure is aimed atablating and repopulating the immune repertoire by first mobilizing and harvesting stem cells from the patient’s ownbone marrow, administering an immunosuppressive treatment, and then re-infusing the stem cell.“Non-myeloablative” conditioning regimens utilizing a reduced-intensity chemotherapy to achieve reduction of theimmune system without bone marrow suppression have been proposed to improve safety and tolerability. A clinicaltrial with non-myeloablative autologous haematopoietic stem cell transplantation reported clinical improvement andinflammatory stabilization in treated patients with highly active multiple sclerosis. Aim of the present study was tounderstand the changes in the reconstituted immune repertoire bearing potential relevance to its mode of action.Blood cells were obtained from 12 patients with multiple sclerosis participating in the aforementioned trial andlongitudinally followed for two years. We examined the phenotype and function of peripheral blood lymphocytes bycell surface or intracellular staining and multi-colour fluorescence activated cell sorting.During immune reconstitution post-transplantation CD4+ FoxP3+ T cells and CD56high NK cell subsets, associatedwith immunoregulatory function, increased their proportions. In contrast, a CD161high proinflammatory CD8+ T cellsubset was virtually ablated at all time-points post-transplantation, but not significantly reduced in patients treatedwith conventional interferon-β immunotherapy. The expression of T cell receptor Vα7.2 and IL-18Rα revealed thatthe CD161highCD8+ T cells were mucosal-associated invariant T cells, a novel cell population originating in the gutmucosa but expressing the central nervous system-homing receptor CCR6. Detection of central nervous system-infiltrating mucosal-associated invariant T cells in post-mortem multiple sclerosis brain white matter active lesionsconfirmed their involvement in the disease pathology. Characterization of this T cell subset by intracellular cytokinestaining demonstrated IFN-γ and IL-17 production and lack of IL-10 production, demonstrating a pro-inflammatorycytokine profile. Mucosal-associated invariant T cell frequency did not change after interferon-beta treatment andwas more profoundly depleted after autologous haematopoietic stem cell transplantation than in patients who hadreceived high-dose cyclophosphamide or alemtuzumab treatment alone, suggesting an additive or synergistic effectof the conditioning regime components.We propose that a favourably modified balance of regulatory and pro-inflammatory lymphocytes underlies thesuppression of central nervous system inflammation in patients with multiple sclerosis following non-myeloablativeautologous haematopoietic stem cell transplantation with a conditioning regimen consisting of cyclophosphamideand alemtuzumab.MS_FrontiersHandbook_2013v2withSash.indd 29 25/04/2013 11:24
  30. 30. 30Abstracts2. Remyelinating gene therapy by PDGFA delivered as a latent growthfactor activated by inflammationAnnenkov A, Helene Gautier, Robin Franklin, David Baker, Charles ffrench-Constant, Yuti ChernajovskyBone and Joint Research Unit, Queen Mary University of LondonWe explore the possibility of promoting CNS remyelination using the oligodendrocyte progenitor (OPC) mitogenPDGFA produced in a biologically inactive form that can be activated by matrix metalloproteinases (MMP). Sucha strategy confines biological activity of PDGFA to sites of neuroinflammation, characterised by increased MMPexpression. The latent state of PDGFA is achieved by fusion with TGFbeta1 latency associated peptide (LAP),with MMP cleavage site between LAP and PDGFA. The recombinant gene for this fusion protein (LmP) has beenproduced together with a number of control genes encoding 1) mouse PDGFA (mPDGFA), 2) the alternativelyspliced long isoform of mPDGFA (mPDGFA_L), 3) mPDGFA tagged with the au1 antigenic epitope at the C-terminus(mPDGFAau1), 4) a fusion protein without MMP cleavable site (L_P). Both fusion proteins LmP and L_P are taggedwith au1 at the C-terminus. Each of the five genetic constructs has been subcloned in constitutive and induciblelentiviral vectors for testing feasibility of this regenerative treatment in a number of experimental models, including invitro differentiation of OPC, ethidium bromide-induced demyelination, and experimental allergic encephalomyelitis.Lentiviral particles containing genes for these genetic constructs have been produced and used for geneticmodification of primary OPC and the OPC line CG4. After optimisation of primary OPC transduction, geneticallyengineered cells will be tested in vitro and in the demyelination models in vivo. The recombinant proteins havebeen biochemically and functionally characterised using serum-free culture supernatants conditioned by 293T cellsthat had been transduced with lentiviral vectors containing genes for these proteins. After treatment with MMP-1,PDGFA was released from LmP, but not from L_P, as shown by immunoblotting with an anti-au1 antibody. PDGFAexpressed as a free protein and PDGFA released from LmP promoted growth of CG4 cells. Genetically modifiedprimary OPC and CG4 cells expressing the recombinant PDGFA constructs will be also used for modelling effects ofautocrine and paracrine secretion of PDGFA on OPC growth and differentiation.MS_FrontiersHandbook_2013v2withSash.indd 30 25/04/2013 11:24
  31. 31. 31Abstracts3. Research Network: Involving people affected by MS in shaping researchAlison Astles1, Peter Bailey1, Sarah Bittlestone1, Neil Forbes1, Karen MacRae1, Sue Polson1, Sarv Kaur21Research Network steering group members, MS Society2Public Involvement Officer, MS Society‘We are committed to involving people affected by MS in every aspect of our work.We believe that only by fully involving people affected by MS in our research programme can we ensure that ourwork reflects the needs, wishes and aspirations of people affected by MS.’ –MS Society Research Strategy, 2013-2017.The MS Society’s award winning Research Network has over 300 members, all affected by MS, who are committedto working along side researchers to improve the quality and relevance of MS research projects.Within the MS Society, Research Network members are involved in a range of activities: developing researchpriorities, reviewing grant applications, influencing funding decisions, supporting projects by sitting on steeringgroups and management boards, and communicating messages about research.Members of the Research Network offer a wealth of experience and knowledge. When designing and implementingresearch projects researchers are able to draw on their expertise to strengthen their research projects.The MS Society has a dedicated Public Involvement Officer, Sarv Kaur, who supports public involvement in research.The Public Involvement Officer works closely with both the Research Network and with researchers, assistingresearchers to improve the way people affected by MS are involved in shaping research. The MS Society also hasa Research Network steering group made up of Research Network members who advise the MS Society on thedevelopment and direction of the Research Network.Researchers are encouraged to involve people affected by MS at the very earliest planning stages. There are manyways researchers can involve the Research Network in their research, some of which include:• Reviewing research proposals for relevance and commenting on methods proposed to ensure they areacceptable and sensitive to potential research participants• Commenting on, and developing accessible, information sheets, leaflets, posters, questionnaires etc prior todissemination to the wider MS community• Sitting on steering groups or project management boards• Participating in meetings or focus groupsResearchers can find out more about working with the Research Network by contacting Sarv Kaur by or calling 020 8438 0921.MS_FrontiersHandbook_2013v2withSash.indd 31 25/04/2013 11:24
  32. 32. 32Abstracts4. A qualitative study of emotional experiences and help-seekingin women with MS*Blundell Jones J, Sue Walsh, Claire IsaacUniversity of SheffieldBackground: High prevalence rates of depression and anxiety have been reported in Multiple Sclerosis (MS).Treatments are effective but evidence suggests that individuals do not always seek help for emotional difficulties.Help-seeking is influenced by factors such as perceptions of need and stigma.Objectives: To develop understanding of the emotional experiences of people living with MS, and to explore howsuch experiences are coped with and understood.Design: Qualitative study with semi-structured interviews and follow-updiscussions. Interviews were analysed using Interpretative Phenomenological Analysis.Participants: Ten women with a diagnosis of MS aged between 30 and 64.Setting: A regional MS Clinic.Results: Four overarching themes emerged from the data: Disclosure stress, Uncomfortable dependence, Facingdeterioration and One step at a time.Decisions regarding sharing their diagnosis were difficult for the women as neither disclosure nor non-disclosurewas problem-free. Physical help from others was needed and valued but affected the women’s sense of self. MSthreatened further life changes due to symptom unpredictability, coping with this threat and facing losses could beoverwhelming. The emotional impact was a significant part of their lives but felt invisible to others especially services.They worked hard to “keep going” physically (to managesymptoms) as well as emotionally, and found strategies to avoid depression and anxiety. Women understood theiremotional experience in different ways but it appeared that reaching a point of feeling unable to cope with emotionswould stimulate help-seeking.Conclusion: Women struggled emotionally with many aspects of living with MSyet coping alone was a way of defying it and maintaining independence and control. Although women sometimesneeded emotional support, it seemed others did not either notice or understand; they wanted services to care moreholistically for them and needed more information. Not seeking help for distress was partially influenced by a desireto keep things ‘normal’ and a lack of knowledge regarding service provision.*Selected for presentation during ‘Mind and body: The interface between psychological and biomedical in MS’MS_FrontiersHandbook_2013v2withSash.indd 32 25/04/2013 11:24
  33. 33. 33Abstracts5. Mindfulness based cognitive therapy for people affected by primaryand secondary progressive Multiple SclerosisBogosian, A, Prof. Rona Moss-Morris, Prof. Paul ChadwickKing’s College LondonMindfulness based interventions have been shown to reduce stress, depression and anxiety symptoms, improvequality of life and decrease physical symptoms for people with a range of chronic conditions, including MS.The aims of the project are:1. To develop a distance delivered 8-week Mindfulness-Based Cognitive Therapy (MBCT) programme forpeople with progressive MS.2. To gain a better understanding of the potential benefits of MBCT for MS by repeatedly measuring processof outcome measures across the programme.3. To assess people’s experiences of the MBCT so that further modifications can be made to the protocol.A detailed manual and protocol have been written for this study. The first stage of the evaluation included two peopleaffected by progressive MS. They took part in the programme on a one-to-one basis and gave detailed feedback.The second stage involved one group of 4 people with progressive type of MS.Participants took part in the mindfulness programme. The programme was delivered via Skype video-conferences.The sessions lasted one hour and took place once a week, over an 8-week period. Participants completedquestionnaires 3 weeks before the programme started, at the beginning and end of the programme; processmeasures were also completed weekly. In the end of the programme participants gave detailed feedback through atelephone interview with an independent researcher.Questionnaire data were plotted and visually inspected for each case to determine change over time. To get anestimate of the changes on the primary outcomes, the data for each individual case were analysed using regressionanalysis. Feedback interviews were analysed using thematic analysis.Overall participant found the programme relevant and useful but also identified some problems, which are nowaddressed. These problems included technical aspects of the interventions (Skype, online questionnaires), contextissues (some concepts needed more time to be explored or more relevant examples) and more informationregarding mindfulness and association with MS was needed. The results of these case studies were used to furthermodify the mindfulness programme for people with progressive MS for the pilot randomised controlled trial that weare currently conducting.MS_FrontiersHandbook_2013v2withSash.indd 33 25/04/2013 11:24
  34. 34. 34Abstracts6. Dorsal root ganglia in MS: histological and mitochondrial changesCampbell, G, Jessica A Santivanez, Elizabeth Bradbury, Doug M Turnbull, Bruce G Trapp,Hans Lassmann, Don MahadUniversity of EdinburghIntroduction: In MS, sensory symptoms and findings are prevalent and they are understood to be the manifestationof central nervous system (CNS) pathology. Despite the involvement of centrally projecting axons of dorsal rootganglia (DRG) neurons and the proposal that DRG neurons are metabolically compromised (Waxman, 1993), DRGhave not been studied in MS patients.Methods: We histologically characterized cervical and lumbar DRG, obtained at post-mortem, from progressiveMS (n=16), motor neuron disease (n=4), Parkinson’s disease (n=3) and controls (n=12) and explored DRG neuronalmitochondria. Lumbar DRG were also derived from a thoracic spinal cord crush injury model. Histochemical andimmunohistochemical methods were used for both human and animal tissue. Molecular techniques included long-range, real-time and single molecule PCR and sequencing of laser captured single DRG neurons from post-mortemtissue.Results: The cellularity of DRG was increased in MS compared with controls, with evidence of perineuronal glialreaction (satellitosis) and greater HLA-positive elements. Total neuronal counts were decreased by 31% in lumbarDRG from MS cases compared with controls. The size and density of DRG neurons, however, were not significantlydifferent in MS compared with controls. Retrograde neuronal changes (central chromatolysis) were evident in aminority of DRG neurons (11.9%) in MS, although significantly more than in controls (2.7%), and apoptotic neuronswere not detected.Strikingly, both lumbar and cervical DRG in MS contained a substantial number of neurons lacking in mitochondrialrespiratory chain complex IV (respiratory deficient) than controls (39% and 24%, respectively, of all DRG neurons inMS versus 3% and 4.5% in controls). The difference in respiratory deficiency between lumbar and cervical DRG inMS was statistically significant (p=0.01).Respiratory deficiency in MND and PD DRG was comparable to controls. In MS, respiratory deficiency wasexplained by high level of clonally expanded mitochondrial DNA (mtDNA) deletions and mtDNA depletion, wheninvestigated in single neurons. Furthermore, subunits of mitochondrial respiratory chain complex I and complexIV were not detected in these neurons, indicative of the pathogenicity of mtDNA deletions. Only a small subset ofrespiratory deficient neurons (9.3%) showed central chromatolysis in MS whilst the spinal cord crush injury modelDRG did not contain respiratory deficient neurons (despite 15.6% of chromatolytic neurons), indicating axontransection as an unlikely cause of the DRG neuronal mitochondrial abnormalities in MS.Conclusions: For the first time we show that the DRG in MS are abnormal. The abundance of respiratory deficientDRG neurons, identified here, adds to the previous observations that most upper motor neurons in MS also containdysfunctional mitochondria. Together, these findings suggest that axon length may influence the generation ofmitochondrial abnormalities in the neuronal cell bodies in MS. The mitochondrial abnormalities in neuronal soma,unrelated to axon transection, are likely to have important consequences for the integrity of axons, particularly in theface of demyelination, and for the pathophysiology of progressive MS.MS_FrontiersHandbook_2013v2withSash.indd 34 25/04/2013 11:24
  35. 35. 35Abstracts7. Accurate estimates of whole brain neuronal loss in multiple sclerosis:preliminary results using unbiased quantitative histologyCarassiti, D, Maria M Papachatzaki, Francesco Scaravilli, Klaus SchmiererQueen Mary, University of LondonIntroduction: Evidence suggests neuro-axonal loss is the major substrate of chronic functional deterioration inpeople with multiple sclerosis (pwMS). Whilst acute axonal transection and Wallerian degeneration have beendescribed as mechanisms of axonal damage in and around MS lesions (Trapp et al., 1998, Peterson et al., 2001,Dziedzic et al., 2010), the mechanisms of neuronal injury in the cortex are less clear, though meningeal inflammationmay play a role (Howell et al., 2011). However, there is significant variation of the reported degree of corticalneuronal loss (Wegner et al., 2006, Magliozzi et al., 2010) and the overall loss of neurons and the topographicdistribution of this loss in MS is unknown. Accurate quantification of cell populations including neurons is offundamental importance for a better understanding of MS pathophysiology. We applied unbiased samplingtechniques derived from stereology to quantify neuronal cell counts throughout the neocortex.Methods: Formalin fixed brain hemispheres of two people with secondary progressive MS (one female, one male,age= 47 and 92 years, disease duration= 31 and 60 years, brain weight = 1050g and 1310g respectively) and onereference case (male, age= 78 years, brain weight = 1236g) with no known neurological disease were used. Lobartopography (frontal, parietal, temporal, occipital lobe) was identified and marked with tissue dye on the corticalsurface. One hemisphere was then dissected into 1.1 cm thick coronal slabs, and images obtained of each slabfollowing a standard protocol. Each slab was then embedded in wax and 40μm-thick hemispheric sections wereobtained. To calculate tissue shrinkage images of entire sections at dissection and after embedding were obtained.On the basis of Giemsa staining and morphological criteria neurons were identified and counted using a x60objective on a microscope equipped with a motorized stage controlled by StereoInvestigator software. Stereologicalprinciples were applied as follows: the cortex was outlined on a single section from each block (AOI) and countingboxes (50μm x 50μm x 30 μm) were cast randomly using a constant grid (X: 3455 μm, Y:4655μm) for all samples. The number of neurons in each slab was subsequently calculated according to NV x NREFstereology method: NV = total neurons counted/volume of all counting boxes and NREF = AOI x cortical thickness.Results: Cortical neurons stereological counts were 17 billion for the 1st and 9.6 billion for the 2nd MS case, and19.8 billion for the control brain.Discussion: To the best of our knowledge, this is the first study to estimate total neuronal loss in MS cortex usingthe most accurate principles technology (stereology). The total number of neurons we obtained in our controlcase was similar to figures reported previously in a larger cohort (Pelvig et al., 2008). Future work will focus on (i)expanding our sample size, (ii) including further cell populations (T B cells, microglia/macrophages, astrocytes)and morphological features (eg. neuronal size synaptic arborisation), and (iii) investigating the associationbetween tissue damage in the cortex and the spinal cord to explore whether a tract specific pattern of neuro-axonaldegeneration contributes to chronic disease progression in MS (Kolasinski et al., 2012).MS_FrontiersHandbook_2013v2withSash.indd 35 25/04/2013 11:24