SSIF Satellite Symposium at ENS

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1 FINAL PROGRAMME AND ABSTRACT BOOK Xxx Xxx, Xxx 1 Xxx Xxx, Xxx 2 Xxx Xxx, Xxx 3 SSIF Satellite Symposium at ENS Amyotrophic lateral sclerosis: where do we stand? Barcelona, Spain - 9 June 2013 References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14, I

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3 General information Venue The satellite symposium takes place at the: Barcelona Congress Center Av. Diagonal, Barcelona Spain Tel.: Language The official language of the symposium is English. Scientific secretariat Serono Symposia International Foundation Salita di San Nicola da Tolentino, 1/b Rome, Italy Associate Project Manager: Simona Gaudiosi Specialist Medical Advisor: Federica Cerri Tel.: +39 (0) Fax: +39 (0) Serono Symposia International Foundation is a Swiss Foundation with headquarters in 14, rue du Rhône, 1204 Geneva, Switzerland To know more visit: 1

4 SSIF Satellite Symposium at ENS Amyotrophic lateral sclerosis: where do we stand? Serono Symposia International Foundation symposium on: Amyotrophic lateral sclerosis: where do we stand? Barcelona, Spain - 9 June 2013 Aim of the live educational symposium Amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological disorders, with very limited therapeutic options. Since its first description by Charcot in 1869, tremendous progress has been made based on recent neuropathological and genetic discoveries that shifted the emphasis to ALS as a complex disorder not only affecting motor neurons. Moreover, the evolution of MRI techniques over the last decades has offered the opportunity to gain insights into the ALS pathology and opened new strategies to find out potential biomarkers to facilitate an early diagnosis and as a tool to predict and monitor disease progression. Even though new potential therapeutic targets have been identified, the available treatment options are still inadequate to prevent a fatal course. The aim of this symposium is to provide the most updated overview on ALS genetics, MRI features and therapeutic strategies. Learning objectives After attending this live educational symposium the learners will be able to: Classify genes and clinical phenotypes that have been described in different sets of ALS patients Apply a full genetic evaluation to both familial and sporadic cases of ALS Compare different MRI techniques and explain how to apply them in clinical practice and in an experimental setting Report the new potential therapeutic targets and their role in ALS pathogenesis Review the new molecules that are on trial and list the level of evidence concerning the drugs available for ASL treatment Target audience Neurologists directly involved in the management of patients affected by ALS; all neurologists interested in being updated on ALS. Scientific organizer Giancarlo Comi Department of Neurology Institute of Experimental Neurology Vita-Salute San Raffaele University Milan, Italy All Serono Symposia International Foundation programmes are organized solely to promote the exchange and dissemination of scientific and medical information. No forms of promotional activities are permitted. There may be presentations discussing investigational uses of various products. These views are the responsibility of the named speakers, and do not represent an endorsement or recommendation on the part of Serono Symposia International Foundation. This programme is made possible thanks to educational grants received from: Arseus Medical, Besins Healthcare, Bristol-Myers Squibb, Celgene, Centre d Esclerosi Multiple de Catalunya (Vall d'hebron University Hospital), Centre Hépato-Biliaire, Hôpital Paul Brousse, ComtecMed, Congrex, Croissance Conseil, Cryo-Save, Datanalysis, Dos33, Esaote, European Society of Endocrinology, Ferring, Fondazione Humanitas, Fundación IVI, GE Healthcare, GlaxoSmithKline Pharmaceuticals, IPSEN, Johnson & Johnson Medical, ISFP International Society for Fertility Preservation, ISMH International Society of Men s Health, K.I.T.E., Karl Storz, Lumenis, Merck Serono Group, PregLem, Richard Wolf Endoscopie, Sanofi-Aventis, Stallergenes, Stopler, Teva Pharma, Toshiba Medical Systems, Université Catholique de Louvain (UCL), University of Catania. 2

5 Accreditation Serono Symposia International Foundation ( is accredited by the European Accreditation Council for Continuing Medical Education (EACCME ) to provide the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical Specialists (UEMS), The SSIF Satellite Symposium at ENS: Amyotrophiclateral sclerosis: where do we stand to be held in Barcelona, Spain on 9 June 2013, is designated for a maximum of 1 (one) hour of European external CME credits. Each medical specialist should claim only those hours of credit that he/she actually spent in the educational activity. Through an agreement between the European Union of Medical Specialists and the American Medical Association, physicians may convert EACCME credits to an equivalent number of AMA PRA Category 1 Credits. Information on the process to convert EACCME credit to AMA credit can be found at Live educational activities, occurring outside of Canada, recognized by the UEMS-EACCME for ECMEC credits are deemed to be Accredited Group Learning Activities (Section 1) as defined by the Maintenance of Certification Program of The Royal College of Physicians and Surgeons of Canada. Serono Symposia International Foundation adheres to the principles of the Good CME Practice Group (gcmep) follow us on SSIF_Neurology 3

6 Scientific programme Sunday - 9 June Serono Symposia International Foundation (SSIF) Opening G. Comi (Italy) Chairmen: G. Comi (Italy) - V. Silani (Italy) L1: Patho-physyological updates on amyotrophic lateral sclerosis A.C. Ludolph (Germany) Discussion L2: MND spectrum: MRI features F. Agosta (Italy) Discussion L3: Therapy: state of the art and unmet needs O. Hardiman (Ireland) Discussion Concluding remarks End of the symposium 4

7 Federica Agosta Giancarlo Comi Orla Hardiman Albert C. Ludolph Vincenzo Silani Faculty members

8 Biographies Federica Agosta Neuroimaging Research Unit Institute of Experimental Neurology, Division of Neuroscience San Raffaele Scientific Institute, Vita-Salute San Raffaele University Milan, Italy Federica Agosta was born in Milano on 01/04/1978, took her Graduation in Medicine in 2003 and her Post-Degree Graduation in Neurology in Federica Agosta has a broad background in clinical neurology and neuroimaging, with specific training and expertise in neurodegenerative diseases. As research fellow at the Neuroimaging Research Unit, Scientific Institute San Raffaele, Milan, Italy she collaborated in several research projects on the use of conventional and quantitative magnetic resonance techniques in the study of normal aging, amyotrophic lateral sclerosis, Parkinson s disease, and multiple sclerosis. During those years she has improved her knowledge on acquisition and post-processing techniques applied to functional MRI, diffusion tensor imaging and morphometry. As a postdoctoral fellow at the Memory and Aging Center, UCSF, she expanded her knowledge on AD, frontotemporal dementia, and primary progressive aphasia. Federica Agosta is currently a clinical researcher at the Neuroimaging Research Unit, Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy, where she conduct research projects in patients with dementia and other neurodegenerative conditions. She is member of the ENS, in which she participates actively to the Neuroimaging Subcommittee, and Neuroimaging Symposium in ALS (NISALS). She acts as a reviewer on a regular basis for several international scientific journals and Governmental Organizations. Federica Agosta is author or co-author of more than 100 scientific papers published on peer-reviewed journals (H index: 24). In 2010, Dr. Agosta has been selected as young researcher participant for the 60 th Interdisciplinary Meeting of Nobel Laureates for her outstanding contribution to the application of MRI techniques to the study of neurological diseases. Giancarlo Comi Department of Neurology Institute of Experimental Neurology Vita-Salute San Raffaele University Milan, Italy Giancarlo Comi received his degree in medicine in 1973 and neurological certification in 1977, both from the University of Milan, Italy. He joined the Department of Neurology, Scientific Institute San Raffaele, University of Milan, in 1974 as a Clinical Assistant and in 1988 was appointed Assistant Professor in Clinical Neurophysiology. Currently he is Professor of Neurology, Chairman of the Department of Neurology, and Director of the Institute of Experimental Neurology at Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan. Professor Comi s areas of interest are principally directed towards the study of the pathophysiology and treatment of MS. He has authored and co-authored more than 800 articles in peer-reviewed journals and edited eight books. He has a long-standing involvement as an active member of the steering committees and advisory boards of many international clinical trials, mainly in the field of MS. Professor Comi is the Vice President of the European Charcot Foundation and member of the Board of Administration of the Italian Multiple Sclerosis Foundation and the Scientific Committee of the Italian Multiple Sclerosis Association. Professor Comi has also served as President of the European Neurological Society and the Italian Society of Clinical Neurophysiology. He is currently the President of the Italian Society of Neurology. Professor Comi currently sits on the executive boards of various scientific associations and on the editorial boards of Clinical Neurophysiology, European Neurology and Multiple Sclerosis and is the Associate Editor of Neurological Sciences. 6

9 Orla Hardiman National Neuroscience Center of Ireland Beaumont Hospital Trinity College Dublin Dublin, Ireland Prof. Hardiman was born in Dublin and educated through Gaelic. She is a graduate of University College Dublin: She was awarded a B.Sc. (first class honours) in Physiology (1980); First place in Medicine in her final MB.BCh.,BAO in 1983, and her MD in She underwent post graduate training in Dublin, and subsequently moved to Boston to undertake Neurology Residency training at Harvard Longwood Neurology Program where she was Chief Resident in Neurology ( ). Her Fellowship training was in Neuromuscular Disease at Massachusetts General Hospital and Harvard Medical School, Boston under the mentorship of Robert H Brown Jr. She returned to UCD in 1991 as a Newman Scholar in the Dept Physiology in University College Dublin, and was appointed to position of College Lecturer in Physiology at UCD in She was appointed as a Consultant Neurologist at Beaumont Hospital in 1996, and became a Fellow of Royal College of Physicians in Ireland in In 2004, she became the first Irish-based Neurologist to become a Fellow of the American Academy of Neurology. She is one of 11 Health Research Board Clinician Scientists. Prof. Hardiman is the recipient of a number of honours and awards, including the first American Academy of Neurology Palatucci Award for Advocacy in Neurology (2003), the prestigious ALSA /American Academy of Neurology Sheila Essay Award in ALS (2009) and the International ALS Alliance Forbes Norris Award in Her primary research interests include the epidemiology, causes and new treatments for amyotrophic lateral sclerosis. Recent work focuses on the clinical and genetic overlap between ALS and frontotemporal dementia and the epidemiology, clinical features and health service needs of people with these and other forms of young onset neurodegeneration. Prof. Hardiman is an author of over 170 international peer-reviewed research articles, a textbook on Neurodegeneration, and is a member of number of national and international boards and advisory panels. She is current Dean of the Irish Institute of Clinical Neuroscience (IICN) and Deputy Chair of the European Network for Cure of ALS (ENCALS). In 2008 she was elected the Editor-in-Chief of the journal Amyotrophic Lateral Sclerosis and Frontemporal Degeneration, which is the official organ of the World Federation of Neurology Research group in Motor Neurone Disease. Prof. Hardiman s research is funded by the HRB, the Charity Research Motor Neuron, and Health Seventh Framework Programme (FP7/ ) under grant agreement n Albert C. Ludolph Department of Neurology University of Ulm Ulm, Germany Prof. Albert Christian Ludolph is Professor of Neurology and Chairman of the Department of Neurology at the University Hospital and Medical Faculty of Ulm. He is also acting Director of the Academic Neuroscience Centre of the University of Ulm and is the current Chair of the European ALS-Group. He has established and leads the ALS-Centre at the University Hospital of Ulm and directs a multidisciplinary team for ALS care, clinical and experimental research. His scientific interests are: clinical Studies in neurodegenerative diseases (current focus: ALS, FTD, MSA, PSP, Huntington s disease), preclinical research in neurodegenerative disease (current focus: ALS, FTD, PSP, MSA, Huntington s disease), genetics and pathogenesis of ALS / MND and neurotoxicology (metabolism, pharmacology). 7

10 Biographies Vincenzo Silani IRCCS Institute Milan, Italy Dr Silani is Professor and Chairman of the Department of Neurology - Stroke Unit and Laboratory of Neuroscience at the University of Milan Medical School - IRCCS Istituto Auxologico Italiano, Milano with the Residency Program in Neurology (2002-present); Director Dino Ferrari Centre for Neuromuscular and Neurodegenerative Diseases of the University of Milan Medical School at the IRCCS Istituto Auxologico Italiano, Milano (2002-present). As neuroscientist he has been interested in ALS since 1977, contributing in many areas in both basic and clinical science. He is Director of the Laboratory of Neuroscience with a large number of Ph.D.s He developed an ALS Center in Milan with a large database of SALS/FALS and a large collection of biological samples. He founded the SLAGEN Italian Consortium and completed one of the largest GWA for SALS. He largely contributed in defining the expression of different genes in both SALS and FALS, investigating the functional role of TDP43, FUS/TLS, and C9ORF72. He has been P.I. of many clinical trials in ALS and recipient of many national and international grants. He has been awarded by AriSLA with the project EXOMEFALS and NOVALS, aiming at the identification of new genes in FALS using exon capture and short-read sequencin (Profilin1). Stem cells have received a large interest along the years as demonstrated by many contributions. More recently he is interested in FTD and HD as well, largely contributing also to these areas of research. Author of 193 peer reviewed papers. 8

11 Abstracts

12 L1 - Patho-physyological updates on amyotrophic lateral sclerosis Albert C. Ludolph Department of Neurology, University of Ulm, Ulm, Germany During the past two decades the ideas on the pathophysiology of ALS were strongly influenced by genetics and the description of multiple genes such as SOD1, FUS, TDP43 and C9ORF72. However, in spite of intensive research into their pathophysiology none of the genes has a major impact on our current mechanistic understanding of either the genetic or the sporadic disease. Most importantly, none has led to therapeutic advances. Therefore, it is interesting to note that the clinical and pathophysiological concept of ALS is undergoing a radical change presently. There are two major novel concepts: 1. It was already described in 1889 that ALS is associated with familial or genetic psychiatric diseases which have an impact on behaviour. This concept was forgotten by many until a decade ago; now, the concept that ALS and frontotemporal dementias (FTDs) frequently overlap is widely accepted (1). 2. Very recently, the longitudinal neuropathology of ALS has been described by using the protein TDP-43 as a molecular marker ( Braak stages of ALS ) (2). This longitudinal staging clearly indicates that the TDP-43 neuropathology is beginning in the motor cortex and that the four stages of the neuropathology affect one efferent pathway after the other with the corticospinal and bulbar tract being the first. Most importantly, they show that the concept of initiation and propagation of disease as described in Alzheimer s and Parkinson s disease by the Braaks - should be considered for ALS as well. These new concepts have already led to a redefinition of the genetics of ALS and FTD and may lead to a reinterpretation of genetic findings with regard to disease initiation and propagation. They show that only a thorough clinical and neuropathological/neuroanatomical description of phenotypes will lead to a correct interpretation of molecular findings. References: 1. Neumann M et al. (2006) Science 314: Brettschneider J et al., Ann Neurol., in press. 10

13 L2 - MND spectrum: MRI features Federica Agosta 1, Massimo Filippi 1,2 1 Neuroimaging Research Unit, and 2 Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy There is as yet no definitive diagnostic test available for MND. Diagnosis is mainly on clinical grounds, with the use of paraclinical and laboratory tests to exclude other causes. The greatest contribution of neuroimaging of the brain and the spinal cord to the diagnosis of MND so far has been its sensitivity to detect changes suggestive of alternative diagnoses. The detection of corticospinal tract (CST) hyperintensities on conventional MRI and a T2-hypointense rim in the precentral gyrus can support a pre-existing suspicion of MND. However, the specific search of these abnormalities for the purpose of making a firm diagnosis of MND is not recommended. Over the past 10 years, there have been significant advances in the identification of advanced neuroimaging patterns in MND. As in other neurodegenerative conditions, the value of these (supportive) features in the clinical diagnosis of MND should be acknowledged. Indeed, in the absence of definitive biomarkers of upper motor neuron (UMN) involvement, a significant cortical thinning of the precentral gyrus, damage to the CST and corpus callosum assessed using diffusion tensor MRI, and altered N- acetylaspartate levels in the primary motor cortex and CST should be considered consistent with MND and hold promise for assessing the UMN involvement before clinical symptoms become apparent. Importantly, DT MRI measures of the CST have a prognostic value in amyotrophic lateral sclerosis patients. Furthermore, patterns of brain damage are emerging to identify patients prone to develop dementia or have a rapid progression. It is strongly advisable to incorporate measures derived from advanced MRI techniques into new clinical trials as exploratory outcomes to gain additional insights into the value of these techniques in the assessment of MND in the individual patient and to validate them further in the context of multicenter, longitudinal studies. 11

14 L3 - Therapy: state of the art and unmet needs Orla Hardiman National Neuroscience Center of Ireland, Beaumont Hospital, Trinity College Dublin, Dublin, Ireland ALS is a recognizable condition that characteristically involves a pattern of progressive motor neuron loss, culminating in respiratory failure and death within 3 years of first symptom. A mendelian inheritance pattern is present in a minority, and mutations in SOD1 were first identified in some cases of familial ALS in A transgenic mouse model was rapidly developed that recapitulated in part the human ALS phenotype. The past 20 years has witnessed a disappointing absence of drugs that meaningfully impact disease progression in the msod1 mouse, and translation of apparently beneficial drugs to humans has been singularly unsuccessful, leading to a reappraisal of the utility of the model. The recent disappointing outcome of a large Phase III trial of dexpramipexole, despite positive findings in Phase II and the development of a novel outcome measure, has also raised valid concerns regarding current clinical trial design in ALS. Recent advances in human genetics and detailed phenotyping and imaging studies at ALS have together provided compelling evidence of disease heterogeneity. Detailed cluster analysis of population based datasets can identify distinct prognostic groups with differing phenotypic characteristic. These insights, coupled with recent discovery of mutations in genes that regulate RNA metabolism (TDP43, FUS and ANG) and the presence of an intron hexanucleotide expansion on Chromosome 9p21 in up to 11% of all ALS, and up to 50% of familial disease, have radically altered the direction of ALS research. New drug development may shift from the search for a magic bullet to the search for compounds with a number of different actions, reflecting the complexity of disease pathogenesis. It is also likely that future clinical trials will require careful stratification of patients both by genotype and by prognostic group. Where there are limited pharmacological options in ALS, the mainstay of management remains symptomatic. Access to multidisciplinary care, early introduction of non-invasive ventilation, close attention to nutrition and secretion management, and support at existential level to patients and carers can both improve clinical outcome and enhance quality of life. Timely access to palliative care and appropriate use of symptomatic treatments at end of life are also essential components of ALS care. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

15 Disclosure of faculty relationships Serono Symposia International Foundation adheres to guidelines of the European Accreditation Council for Continuing Medical Education (EACCME) and all other professional organizations, as applicable, which state that programmes awarding continuing education credits must be balanced, independent, objective, and scientifically rigorous. Investigative and other uses for pharmaceutical agents, medical devices, and other products (other than those uses indicated in approved product labeling/package insert for the product) may be presented in the programme (which may reflect clinical experience, the professional literature or other clinical sources known to the presenter). We ask all presenters to provide participants with information about relationships with pharmaceutical or medical equipment companies that may have relevance to their lectures. This policy is not intended to exclude faculty who have relationships with such companies; it is only intended to inform participants of any potential conflicts so that participants may form their own judgements, based on full disclosure of the facts. Further, all opinions and recommendations presented during the programme and all programme-related materials neither imply an endorsement nor a recommendation on the part of Serono Symposia International Foundation. All presentations represent solely the independent views of the presenters/authors. The following faculty provided information regarding significant commercial relationships and/or discussions of investigational or non-emea/fda approved (off-label) uses of drugs: Federica Agosta Declared receipt of grants and contracts from Italian Ministry of Health. Declared receipt of honoraria or consultation fees from Biogen Idec. Giancarlo Comi Declared receipt of honoraria or consultation fees from Serono Symposia International Foundation, Novartis, Teva Pharmaceutical Ind., Sanofi, Genzyme, Merck Serono, Biogen, Bayer, Actelion. Orla Hardiman Declared receipt of grants and contracts from the Irish Health Research Board, and from Biogen Idec. Declared receipt consultation fees from: Biogen Idec, Cytokinetics and Novartis. Declared to be Member of the Board of Directors of the Irish Institute of Clinical Neuroscience, The Irish Academy of Medical Sciences and Research Motor Neurone. Albert C. Ludolph Vincenzo Silani Declared to be member of a company advisory board, board of directors or other similar group of Biogen Idec. Declared receipt of grants from Italian ARI Sla2012 (Novals) and Italian Ministry of Health. Declared receipt of consultation fees from Biogen Inc for ALS trial development. 13

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20 Improving the patient's life through medical education Serono Symposia International Foundation Headquarters 14, Rue du Rhône Geneva, Switzerland Representative Office Salita di San Nicola da Tolentino 1/b Rome, Italy T +39.(0) F +39.(0) Copyright Serono Symposia International Foundation, All rights reserved.