INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE Brain & Spine institute - PARIS SEARCH, FIND, CURE, FOR YOU & WITH YOU P 4 - EDITORIALS P 7 - ORGANIZATION OF RESEARCH AT THE ICM P 15 - 2014 in REview P 17 - RESEARCH P 59 - THE IHU-A-ICM P 69 - TECHNICAL PLATFORMS P 97 - THE CLINICAL INvESTIGATION CENTER P 105 - RESEARCH APPLICATIONS TABLE OF CONTENTS OF TABLE P 109 - KEY FIGURES P 117 - LIFE AT THE ICM P 125 - GOvERNANCE, OvERSIGHT, AND TRANSPARENCY Introductory Présentation remarks des équipes by the Presidentde l’Institut and Director-General of the ICM Presentation of the teams of the institute 1 - Neurodegenerative diseases 2 - Multiple sclerosis 1 3 - Brain tumors 4 - Epilepsies 5 - Cognition, behavior, and psychiatric diseases 6 - Modeling 7 - Rare diseases 8 - Basic mechanisms underlying the development and function of the nervous system Glossary 1 - Major achievements 2 - Major publications 2 1 - Molecular exploration 2 - Cellular exploration 3 - Cellular imaging 3 4 - Functional exploration 5 - Preclinical functional exploration- phenoparc 6 - Bioinformatics and biostatistics – iconics 7 - Biological Resource Center 1 - Parkinson’s Disease 2 - Neurogenetics 4 3 - Alzheimer’s Diseases 4 - Multiple sclerosis 5 - Amyotrophic lateral sclerosis 6 - Rare diseases 7 - Understand brain function: motivation 8 - Participatory medicine 1 - Transform knowledge and promote research 2 - iPEPS-ICM companies 5 1 - Fundraising 2 - Use of Resources Statement 6 3 - Balance sheet 1 -Scientific and extra-scientific events 7 2 -Publicity campaigns 1 -Governance and oversight: Board of Administration, Founding Members, Scientific Council,Comité de la charte 8 2 -Friends of the ICM Circle EDITORIAL Hope. It’s the key word for 2014, thanks to the This year, the first international companies arrived at enthusiasm and achievements of our researchers and the ICM: Neoventure Technologies (Ontario), which our partners, growing in numbers by our side. develops new biomarkers for Alzheimer’s disease and PathMaker (Boston), which is developing a method for The year 2013 was encouraging, and 2014 has been electrical stimulation of the spinal cord. rich in discoveries and progress thanks to all those who take part in the daily life of the ICM. To progress it is The iPEPS-ICM obtained seven new patents, and three necessary to takerisksandtryapproachesthatmight projects developed at the iPEPS-ICM won worldwide leadtobreakthroughs at the interface between different innovation competitions: DREEM, Brain-e-NOVATION, scientific fields. In order to advance it is necessary to which is creating e-health solutions, and Bio serenity, develop new unconventional approaches and new which is developing an “intelligent health” solution for methodologies. This is what we have done every day tracking and diagnosing epilepsy. since the inauguration of the ICM in September 2010. Several events also marked the year 2014. A new Many of these discoveries and projects allowed us to publicity campaign was launched, and new supporters progress in our understanding of the diseases of the have joined in this formidable human and scientific brain and spinal cord: adventure. • The discovery of a peptide of viral origin gives Finally, I wish to acknowledge the loyalty of our partners, new hope for patients with Parkinson’s and other sponsors, companies, and regular donors, large and neurodegenerative diseases. The research, conducted small, who contribute every day to build the medicine on mice, demonstrated the existence of a peptide that of tomorrow. can protect against degeneration of neurons implicated in Parkinson’s disease. This discovery gives hope for for The year 2015 will be very important for the institute, th the future of preventing neurodegenerative diseases. which will celebrate its 5 anniversary since opening. 2015 will also be the moment for a first evaluation, • The INSIGHT study was launched in collaboration which we owe to all those who accompanied the with the Institute of Memory and Alzheimer’s Disease development of this center of reference for diseases of (I2MA) and the Pfizer research laboratory in the IHU-A- the nervous system. We will be mobilized so that this ICM. The aim of this five to six year study is to observe year will also be synonymous with new discoveries and andunderstandtheevolutionofAlzheimer’sDisease rich in challenges. My thanks to all of you who made in a cohort of at-risk people in order to identify the the adventure of the ICM possible and who have stood factorsthatinitiatethedisease. 400 healthy subjects alongside us to overcome the diseases of the brain and will be selected to participate in the study. All of these spinal cord. players are motivated to better understand and hope to ultimately treat the disease Since 2012, the ICM has published more than 1000 scientificarticles, with a significant increase in impact factor over time. Additionally, five researchers were honored with prizes: Claire Wyart for the Irene Joliot- Curie prize, Mohammed El Behi for the Foundation Bouvet-Labruyère prize, Luc Mallet for the Marcel Dassault prize, Mathias Pessiglione and Lionel Naccache for the prize of the Academy of Science. All of this attests to the excellence of the 600 researchers, engineers, and technicians at the institute. With six new companies joining in 2014, the business incubator iPEPS-ICM now hosts 20 companies in Professor partnership with the institute. Gérard Saillant President of the ICM EDITORIAL The ICM is on the right track. Already recognized as amajor The ICM is now recognized internationally in the contributor to research on the nervous system and its neurosciencecommunity. This has led to the establishment pathologies, both on the national and international scale, of strategic alliances with the Institute of Neurology (UCL, the major achievements of 2014 illustrate the medical London, UK) and the DZNE (Helmholtz, Germany), with and scientific advances made in a number of domains which the ICM participates in joint European projects. and bear witness to the creativity and engagement of our Exchanges are developing with the Sandler Institute (USCF, researchers and personnel. San Francisco, USA), Yale University (New Haven, USA), and the Florey Institute (Melbourne, Australia), primarily Our new ICM research unit, created on January 1, 2014 among students. A joint workshop was held this year in with our institutional partners, CNRS, INSERM, Pierre Montreal with the Montreal Neurological Institute and and Marie Curie University, is composed of 25 teams Hospital (McGill, Montreal, Canada). Fundraising has also that have been renewed. These teams cover numerous become international, the first international fundraising domains, both fundamental and translational. In order to event took place in London in April 2014. reinforce and vitalize the institute, the ICM and the IHU-A- ICM launched an internationalcallforprojects to recruit The quality of the scientificeventsoftheinstitute is now one or more new teams. Almost a hundred applicants established. Prestigious lectures by eminent international submitted projects and several members of our Scientific figures are complemented by monthly lectures on the Advisory Board came to the ICM to interview a dozen that arts, culture, and science that bring together donors were preselected on the basis of their scientific excellence. and the personnel of the ICM. The institute is an unique Following this procedure, the team directed by Bassem place for training and is associated with Pierre and Marie Hassan was chosen and will join the institute in 2016. We Curie University. Furthermore, thanks to “les Ajités,” an have optimized and reconfigured different parts of the association of students and post-doctoral fellows that building in order to house all of the teams. The organization organizes numerous events, a new dynamic of discussions of the platforms has also evolved with the creation of a and scientific reflection for the youngest members of the Platform Committee for greater reactivity and better Institute has been ushered in. coordination and to anticipate the needs of the researchers Finally, interaction with the business world is accelerating by participating in the technological development of the thanks to the 20 start-ups incubated in the iPEPS-ICM Institute. The first day dedicated to institute platforms that collaborate with local teams, four of which originated allowed us to communicate the capability of these platforms in the ICM. In addition, we organized meetings with to researchers and enterprises, both within and outside the entrepreneurs, and the ICM hosted many events dedicated Institute. Additionally, new platforms were created, such as to innovation and technology transfer. In this context, PRISMEfor the study of behaviors in ecological situations the commercialization of the first licenses for patents or virtual reality, and other platforms were reinforced, generated in the ICM is an encouraging sign. such as with the development of optogeneticsin vivo and the creation of a therapeutic evaluation center (CET) All the elements are thus in place to make the original associated with our Clinical Investigations Center (CIC). ecosystem of the ICM a terrain for veryhighlevelresearch that will not only advance the frontiers of knowledge but The firstinstituteretreat was a moment of discussion and will also develop applications for the benefitofpatients. conviviality during which all personnel could discover the multiple facets of the institute. The retreat was also