INSTITUT DU CERVEAU ET DE LA MOELLE ÉPINIÈRE ICM BRAIN & SPINE INSTITUTE,

ANNUAL REPORT 2016

SEARCH, FIND, CURE, FOR YOU & WITH YOU.

INSTITUTION DU CERVEAU ET DE LA MOELLE EPINIERE ÉQUIVALENCES QUADRI ICM_09_2742_LogoAn_Quad 26/08/2009 MAGENTA 70% JAUNE 100% 24, rue Salomon de Rothschild - 92288 Suresnes - FRANCE Tél. : +33 (0)1 57 32 87 00 / Fax : +33 (0)1 57 32 87 87 Web : www.carrenoir.com CYAN 100% MAGENTA 70% NOIR 60% Ce fichie r est un documen t d’exécution créé sur Illustrator version 10.

SUMMARY

Conversation with the President p.6

Conversation with the Chief Executive p.8

Conversation with the Chief Executive of the IHU-A-ICM p.10

THE INSTITUTE

ICM, an innovative and unique model p.14

Our missions p.16

Our values p.18

Our scientific priorities p.20 Sharing leads to progress Highlights and major breakthroughs in 2016 p.22 Women and men p.24 PROFESSOR GÉRARD SAILLANT, ICM PRESIDENT ‘ ‘ Governance p.28

MISSION

A key player at the heart of 21st century challenges p.32 6 What does it mean to do research today? p.34 CUTTING-EDGE RESEARCH

Research programs p.36 ICM, AN INNOVATIVE Research teams p.40 Overview and publication examples p.44

AND UNIQUE MODEL Synergy p.50

Awards and distinctions p.52

TEACHING AND TRAINING p.54

14 NATIONAL AND INTERNATIONAL COLLABORATION p.56 CLINICAL RESEARCH

Center for Clinical Investigation p.58

Nervous System Diseases Center p.60

KNOWLEDGE SHARING & INNOVATION

Research & Technology Development Office p.62

Living Lab & Findmed p.64 86 iPEPS-ICM incubator p.66 SUPPORT OUR MISSION

State-of-the-art technological platforms p.70

34 DILIGENCE AND TRANSPARENCY AT THE HEART OF OUR ACTIONS Financial situation in 2016 p.76 WHAT DOES IT MEAN COMMUNICATION AND PHILANTHROPY

TO DO RESEARCH TODAY? Le Cercle des Amis de l'ICM p.84

Communication p.86

Thank You p.88 THANK YOU

4 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 5 CONVERSATION WITH THE PRESIDENT

PROFESSOR The Brain and Spine Institute came to life six years ago. When we first came up with the idea for the Institute with our GÉRARD SAILLANT founding members and institutional partners, we never imagined it would be such a success. It was a truly daring project. Bringing all

the key players in research on nervous system diseases together,

in one place, illustrates just how involved everyone is, and how

talented.

I would like to take this opportunity to thank our partners, our

researchers and the entire staff at the Institute for their immense

and unwavering support, as well as our donors for their renewed

generosity.

Our 2016 Report is more than a look at the past year: it is a tribute

to those that made our projects possible.

2016 for ICM proved our Institute’s vitality and its involvement

in the world’s great healthcare challenges. International

collaboration, scientific breakthroughs, sharing of knowledge, as

well as numerous awards show how multi-faceted this major player

of French research really is.

Current stakes in research on brain illnesses are extremely high,

especially as our population ages, and society as a whole is faced

with the challenge of “ageing well”. ICM has a large role to play so

that each and every one of us is able to age in the best possible

conditions, maintaining a form of freedom in our actions.

We do not know all that much about this fascinating yet complex

organ we call the brain!

There is so much left to explore. To find, we must first understand. To find, To get there, we need you, and your support. we must first Thank you, truly. understand.

6 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 7 CONVERSATION WITH

THE CHIEF Our Institute brings together diverse women and men from various horizons, where skills EXECUTIVE and knowledge intertwine. This represents an incredible collective wealth. It brings out the best, giving us the opportunity to meet upcoming challenges together.

PROFESSOR ICM combines a critical mass of talented researchers and clinicians who, in their synergy, develop a translational approach to research. The Institute’s location in GÉRARD SAILLANT Paris, at the heart of the Pitié-Salpêtrière Hospital with over 100,000 patients every year, encourages researchers and clinicians to interact. Thanks to the diversity of our activities and the plurality of our expertise, we can take on the challenge of understanding the nervous system. The multidisciplinary approach developed at ICM, along with our risk-taking and technological innovation, are strong assets for scientific and medical research.

ICM is one of a kind. It is open to visitors from around the world, to students, to researchers, and more. Today, more than ever, it is time to open up, encourage creativity, focus on cooperation, collaboration, and share our respective territories. It will not prevent us from rising up to the challenge, and it will not prevent us from stimulating the quest for quality, performance and discoveries. Quite the contrary… What brings us, researchers, students, doctors, technicians, engineers, together is our essential role in this shared mission for the world as a whole. Results from 2016 give our actions meaning and confirm our community’s excellence. These results show that ICM is dynamic, attractive, with exceptional talent, with a demanding strategy and actions taken, in a high-quality work environment. Tangible progress has been made: a balanced budget, on the rise, over 540 scientific publications including 115 with an impact factor over 7, 11 ANR contracts awarded, prototypes designed in our Living Lab, as well as numerous distinctions and awards for our researchers and the hosting of new startups.

2016 also marks the official launch of our roadmap for the years to come. Priorities have been set to maintain, and go beyond, our excellent level. New teams, talented researchers, development of clinical research, instruments for precision medicine, Together, promoting excellence in and nervous system illness training and education, new instruments to encourage entrepreneurship, and development of national and we will be able international partnerships: these make up the foundation needed to accomplish our missions, reach our goals and to become a vital partner in the development of to face future innovative therapy.

challenges. In 2017, we must stay on track and consolidate our community’s excellence and skill in producing knowledge as well as breakthrough discoveries.

I would like to extend a very warm thank you to all the individuals who, every single day, contribute to our venture: the 650 women and men at the Institute, our partners, donors, and our volunteers, for their immense support.

8 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 9 CONVERSATION WITH THE CHIEF EXECUTIVE OF THE IHU-A-ICM

The IHU-A-ICM’s mission is to lead a high- 2016 was a year filled with success, including FRÉDÉRIC level project for patient care, training, and ambitious clinical trials. The INSIGHT study in SALAT-BAROUX technology transfer in the field of nervous partnership with Pfizer, an innovative study on system diseases research. Its priority is to Alzheimer’s disease, is one of the first worldwide encourage the development of innovative to monitor at-risk healthy individuals, with high preventive, diagnostic, and therapeutic products hopes in gaining a better understanding of the and processes. The results of these past four disease. The ICEBERG cohort is at the heart of years have been overwhelmingly positive. the IHU’s Parkinson’s project, which aims at They allowed us to develop international-level studying predictive conversion and progression research focused on nervous system diseases, factors of Parkinson’s disease. We are making on and psychiatry, to create cutting- progress in major projects on Alzheimer’s edge technological platforms, to implement disease, Parkinson’s disease, multiple sclerosis research partnerships with industry players, to to identifying myelin repair strategies, epilepsy train future healthcare professoressionals, to to understand and anticipate seizures and implement international teaching programs, to behavioral disorders that come into play in many carry out large-scale clinical trials for many neurological illnesses. nervous system diseases through participation in national, European and international networks Finally, this year a joint ICM and IHU-A-ICM and to transfer patient care from the hospital to internal call for high-risk projects made it back home. possible to develop fifteen innovative and unique transveral projects, among which the DYNAMO Within the IHU-A-ICM mid-term assessment and project that aims at creating a digital model on request by the International IHU Jury, the for cerebral evolution in Alzheimer’s disease. IHU-A-ICM developed a roadmap with a long- With time, the project hopes to develop a term action plan. IHU-A-ICM and ICM founding high-precision predictive medicine instrument. members came to an agreement on a strategic Another noteworthy project is the lncPD project, plan, approved by the International IHU Jury and that is exploring unknown parts of DNA involved General Investment Commission (Commissariat in Parkinson’s disease. Général à l’Investissement - CGI) in November 2016 following a site visit on October 18, 2016.

This approval allows the IHU-A-ICM to carry IHU-A-ICM FOUNDERS out its strategic plan around eight main topics: recruiting new teams, learning and training, neuroinformatics, industrial promotion, clinical Si la taille du logo ne permet pas la lecture du texte, utilisez la version ci-dessus We are doing everything research, cellular and molecular imaging, big brain theory program (transversal internal we can to increase prevention projects with high potential) and fundraising to and treatment of nervous meet its ambitious goals. system diseases.

10 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 11 THE INSTITUTE

THE BRAIN AND SPINE INSTITUTE (ICM) IS AN INTERNATIONAL RESEARCH CENTER, ONE OF A KIND THROUGHOUT THE WORLD THANKS TO INNOVATION AT THE HEART OF ITS DESIGN AND ORGANIZATION. THE INSTITUTE’S GOAL, AS IT BRINGS TOGETHER PATIENTS, PHYSICIANS, RESEARCHERS AND ENTREPRENEURS IN ONE PLACE, IS TO ALLOW RAPID DEVELOPMENT OF TREATMENT FOR NERVOUS SYSTEM ICM, an innovative and unique model p.14 DAMAGE IN ORDER TO MAKE IT AVAILABLE TO PATIENTS AS EARLY AS POSSIBLE. Our THE WORLD’S BEST SCIENTISTS, HAILING missions p.16 FROM A DIVERSITY OF BACKGROUNDS AND COUNTRIES, ARE IN CHARGE OF DEVELOPING Our values p.18 CUTTING-EDGE RESEARCH AT THE INSTITUTE. TO GIVE RESEARCHERS THE OPPORTUNITY Our scientific priorities p.20 TO TAKE THEIR WORK TO THE NEXT LEVEL

AND PROVIDE HOPE TO PATIENTS. Highlights and major breakthroughs in 2016 p.22

Women and men p.24

Governance p.28

12 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 13 ICM AN INNOVATIVE AND UNIQUE MODEL 2016 2015 2014 2012 2010 2008 540 2006 PUBLICATIONS 3RD NEUROSCIENCE CENTER FOR CENTER IN EUROPE ++++++++ INTEREST OPENING AND THE IPEPS-ICM EXCELLENCE INVESTMENTS BUSINESS INCUBATOR AND FIRST IN IN NEURODEGENERATIVE SCIENTIFIC PRIORITIES ORGANIZATION CONSTRUCTION FOR THE FUTURE IS OPENED THE COUNTRY DISEASES 2016-2025

The Foundation The construction ICM opens its The iPEPS-ICM ICM is ranked Along with its Institute is accredited as and fundraising doors to the first business incubator 3rd neuroscience institutional researchers were a public interest are both launched research teams is opened to center in Europe partners, the to thank for over organization, to finance high- and in 2011 is host innovative and first in the Institute received 540 publications, giving the level research awarded a project startups and country. the “Center for major scientific scientific projects and launched by the provide an optimal Excellence in and medical adventure a acquire cutting- French Higher context for Neurodegenerative breakthroughs, general interest edge tech Education and groundbreaking Diseases” and numerous ICM STORY OVER THE YEARS… aspect to benefit equipment. Research Ministry projects. distinction as awards. 2016 is patients and Health part of the also a strategic Ministry within national plan for year for ICM as it FACED WITH WORLD HEALTHCARE CHALLENGES the “Investments neurodegenerative marks the launch for the Future” diseases. In the of our roadmap IN THE FIELD OF NERVOUS SYSTEM DISEASES AND program. In 2011, same year, thanks that defines our ICM also received to support from scientific priorities TRAUMA, WITHOUT EFFECTIVE TREATMENT TO “Carnot Institute” 100,000 donors, from 2016 to 2025. ERADICATE THEM, AND GIVEN THE RISE IN LIFE excellence the Institute certification. achieved a EXPECTANCY, INNOVATION IS A NECESSITY. balanced financial VISIONARIES EAGER TO CREATE A NEW KIND OF situation. ECONOMIC MODEL BASED ON STRONG PUBLIC AND PRIVATE PARTNERSHIPS CAME TOGETHER: THE FOUNDING MEMBERS OF ICM, INCLUDING CURRENT PRESIDENT PROFESSOR GÉRARD SAILLANT, JEAN Si la taille du logo ne permet pas la lecture du texte, utilisez la version ci-dessus TODT, PROFESSOR LYON-CAEN, AND PROFESSOR YVES AGID, EMBARKED WITH OUR PARTNERS ON THE INCREDIBLE ADVENTURE OF DESIGNING A NEUROSCIENCE INSTITUTE CAPABLE OF FACING THIS MAJOR CHALLENGE OF OUR TIME.

14 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 15 ICM OUR MISSIONS KEY FIGURES FOR 2016

RESEARCH WHERE INNOVATION DRIVES 1 LIVING LAB

ORGANIZATION 649 researchers and clinicians 22 000 SQM 17 CUTTING-EDGE TECHNOLOGICAL PLATFORMS FROM A SCIENTIFIC FROM THE INFINITELY SMALL… 4 MAJOR SCIENTIFIC FIELDS Fundamental research is research turned Molecular and Cellular Neuroscience STANDPOINT, ICM APPROACH towards a discipline’s fundamental fields. Integrated Neurophysiology 26 RESEARCH TEAMS IS INNOVATIVE WITH A This encompasses scientific research that Cognitive Neuroscience does not have a pre-determined financial Clinical and Translational Neuroscience floors 147631 DONORS SEAMLESS, OPEN APPROACH goal when it is conducted. However, this 8 approach is essential: it is what allows us TO RESEARCH. RESEARCH to learn about and understand how bodily ALONGSIDE TRANSVERSAL TOPICS TEAMS ARE INDEPENDENT systems function. Neurogenetics YET LINKED TOGETHER …TO THE INFINITELY LARGE Neuroimmunology Clinical research places individuals at Stem Cells and Repair 13 INNOVATIVE STARTUPS THANKS TO TRANSVERSAL the heart of this all-too- approach. Motor Neurons: from cell bodies to 2016 HIGHLIGHTS Subjects, whether ill or healthy, take RESEARCH PROGRAMS THAT synapses part in protocols that help us increase Study of organelles in neurodegenerative ALLOW FOR SKILL SHARING. our knowledge of a certain pathology or illnesses 276 doctoral and post-doc students treatment. Study of proteinopathies and propagation mechanisms ONE SINGLE DIRECTION Multimodal data analysis Translational research is the essential Rare neurological disease treatment link between fundamental and clinical methodology research. It allows patients to benefit from diagnostic and therapeutic innovation Over 540 publications more quickly. Translational research forms in major international journals the basis of all research conducted at ICM. Bringing these three activities under one roof, in one single direction, means quicker 32 countries represented discovery of new treatments. BASSEM HASSAN INTERNATIONALLY-RENOWNED RESEARCHER 11 INSTITUTE RESEARCHERS joins ICM rewarded for excellence clinical trials 65 in their work GLOBAL RESEARCH BRAIN TUMORS EPILEPSY THAT COVERS PARKINSON’S DISEASE HUNTINGTON’S DISEASE THE EXPANSE MULTIPLE SCLEROSIS DEPRESSION ICM RECEIVES OF BRAIN AND STROKES "CARNOT 3" OCD CERTIFICATION SPINE DISEASES DEPRESSION RARE ILLNESSES ALS ALZHEIMER’S DISEASE SPINE TRAUMA CRANIAL TRAUMA

BRAIN TO MARKET 3RD PLACE VISIT OF ICM SUMMER SCHOOL IN THE 2016 BIG DATA BY THE FRENCH IS A SUCCESS INNOVATION TROPHY PRESIDENT

16 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 17 ICM OUR VALUES OUR VALUES THE DRIVING VALUES OF ICM, SCIENTIFIC EXCELLENCE THE FOUNDATION OF EVERYTHING WE DO, The best researchers are involved with a common goal: to discover ARE AN APPROPRIATE RESPONSE TO THE NEED FOR CUTTING-EDGE RESEARCH ON NERVOUS SYSTEM DISEASES. FIRST AND FOREMOST FOR THE PATIENT Bringing patients, physicians researchers and entrepreneurs together to advance more rapidly than illness FLEXIBILITY To let scientific creativity express itself OPENNESS Create a place for sharing, to encourage interaction with the greater community and industry partners PASSING ON KNOWLEDGE On an national and international level ACCELERATE To apply tomorrow’s solutions as early as possible

18 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 19 ICM OUR SCIENTIFIC PRIORITIES SCIENTIFIC PRIORITIES OUR SCIENTIFIC STRATEGY TO DELIVER ON CHALLENGES 8 PRIORITY AREAS FOR 2016-2025

PREVENT MEANS INHIBITING ILLNESS AND ITS APPEARANCE. RECRUIT new teams TREAT MEANS SLOWING DOWN OR STOPPING PATHOLOGICAL EVOLUTION. DEVELOP COLLABORATION amongst teams and ENCOURAGE A REPAIR MEANS REBUILDING NEURAL CIRCUITS AFTER DAMAGE TO THE NERVOUS SYSTEM. MULTIDISCIPLINARY APPROACH to test new scientific hypotheses RELIEVE TO ALLEVIATE OR ELIMINATE SYMPTOMS SUCH AS MEMORY LOSS, LANGUAGE DISORDERS, PAIN, ANXIETY, DEPRESSION… in an open-minded setting

EMPHASIZE CLINICAL RESEARCH to succeed, within 3 years,

THE GOAL IS TO PRODUCE INTERNATIONAL-LEVEL RESEARCH BY COMBINING in offering new clinically-approved treatment options to patients SCIENTIFIC CREATIVITY AND THERAPEUTIC PURPOSE ACCELERATE DEVELOPMENT OF NEUROINFORMATICS and implement tools ICM’S SCIENTIFIC PROGRAM IS BASED ON THE FOLLOWING VALUES:

Create a research “strike force”, leading to recruitment of the best French researchers for a more predictive form of medicine, with a more quantitative approach ranked by the High Council of Research Evaluation and Higher Education (HCERES) and the in diagnosis, prognosis and treatment best international investigators evaluated by the International Council for Science Make cutting-edge technology research platforms available as well as a high-performance Center for Biological Resources PROMOTE eXCELLENCE IN EDUCATION AND KNOWLEDGE TRANSFER in Develop multidisciplinary “translational” research, in collaboration with industry partners and the best research centers throughout France and the world. neuroscience and the field of nervous system diseases. Our ambition Define priority research areas. is to create a place of learning when interactions are transdisciplinary

REINFORCE SERVICES FOR INCUBATED STARTUPS to help them with more YOUR BRAIN, OUR PRIORITY rapid financing to get products to market more quickly TOGETHER, ICM’S 650 RESEARCHERS, ENGINEERS AND TECHNICIENS ARE WORKING TO: Diagnose neurodegenerative diseases earlier MAKE CUTTING-EDGE EQUIPMENT AVAILABLE TO RESEARCH TEAMS as needed Predict their progress and improve treatment Develop new diagnostic instruments for their research to remain competitive on an international level, Detect new markers Model disease progression to diagnose illness earlier and anticipate treatment stay ATTRACTIVE to build NATIONAL AND INTERNATIONAL PARTNERSHIPS Offer personalized treatment needed to carry out our missions and meet our goals Delay disease progression Repair affected cells Explore new research on causes and mechanisms involved in neurodegenerative diseases REINFORCE FUNDRAISING ACTIVITIES Study neural development mechanisms to answer the following question: why do some brains lose their homeostatic capability, setting the stage for neurodegenerative diseases?

20 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 21 ICM HIGHLIGHTS AND MAJOR BREAKTHROUGHS

BRAIN TO MARKET SUMMER SCHOOL 12 MONTHS OF PROGRESS The “Brain to Market” Summer School, from August 29th to September 2nd 2016 at ICM, combined translational AND DEFINING MOMENTS ICM RECEIVES “CARNOT 3” neuroscience and entrepreneurial learning in an intensive CERTIFICATION training program. This year, participants worked on epilepsy. ICM received Carnot certification renewal, WHAT TO TAKE AWAY FROM OUR KEY MOMENTS as part of the “Carnot 3” program. Carnot Institutes are major players when it comes THE BRITISH MINISTER to supporting public research institute FOR LIFE SCIENCES development and relationships with PUBLICATIONS VISITS ICM ON THE RISE! A WORLD-CLASS businesses. This certification will increase George Freeman, British RESEARCHER JOINS ICM exposure in order to implement large-scale 540 publications Minister for Life Sciences, Bassem Hassan, research projects at ICM and accelerate in major international was welcomed to ICM by neuroscientist, joined ICM discovery and commercialization of patient journals Alexis Brice, ICM and IHU- in January 2016. He leads treatments. A-ICM Chief Executive. the “Brain Development” During their meeting, team and is focused on Minister Freeman and genetic mechanisms that Professoressor Brice covered ICM’s model and organization control early nervous as well as research and development topics, Big Data, system development, from cell specification to neural industry relations and accelerated access to the innovative network development, and on processes involved in products market. neurological diseases. CLEVEXEL PHARMA PHARMA AND ICM IN THE FIGHT LIVING LAB AT THE PARIS AGAINST PARKINSON’S VIVA TECHNOLOGY DISEASE CHALLENGE ICM and pharmaceutical The uCIL Living Lab, launched company Clevexel Pharma, A GOOD RECORD FOR ANR PROJECTS at ICM in 2015, participated in directed par Christian Bloy, ICM teams were awarded 11 ANR projects: 3 as coordinator the first edition of the Paris RD signed a partnership deal and 8 as partner in 2016 for a total of 2,806,588 € versus 3 PLACE IN THE 2016 BIG DATA Viva Technology Challenge to develop new treatment 2 projects awarded in 2015. Additionally, 30 projects were INNOVATION TROPHY that aims to bring investors against central nervous system submitted this year, versus 23 in 2015. Bioserenity, specialized in smart and managers of innovative diseases and, more specifically, healthcare solutions and connected companies together along 2016 – 2025 Parkinson’s disease. medical equipment and Dataiku, with startups from around LAUNCH OF OUR 2 806 588 € producer of Big Data project the world. The uCIL Living ROADMAP acceleration program Dataiku DSS, Lab is involved in coming up ICM’s startegy is focused on won third place for their Medata. with innovations, technology, 8 major areas: recruitment Lab project in the 2016 Big Data products, and services to of new teams, learning & THE FRENCH PRESIDENT VISITS ICM Innovation Trophy. The project, assist with real-life needs in training, neuroinformatics, French President François Hollande was present at ICM during Inter- developed with support from the healthcare in the fields of commercialization, national University-Medical Center Institute (IHU) Day. He attended a Brain and Spine Institute -ICM and neurology and psychiatry. clinical research, cellular presentation of ICM by the management team and a presentation of Télécom ParisTech, aims at speeding & molecular imaging, big the research done by three researchers and clinicians: Claire Wyart, up diagnosis of epilepsy patients: it brain theory program, and Lionel Naccache, and Carine Karachi. He also visited the Magne- uses smart clothing developed by fundraising. toencephalography (MEG) platform with Nathalie George. BioSerenity to collect patient health data, which is then analyzed using the predictive analysis platform developed by Dataiku.

22 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 23 ICM WOMEN AND MEN WOMEN AT ICM

THE INSTITUTE WAS FOUNDED ON THE IDEA THAT FEMALE SCIENTISTS PLAY A FUNDAMENTAL ROLE IN RESEARCH AND A COMMUNITY DEDICATED TO NEUROSCIENCE OUR SOCIETY. A THINK TANK WAS IMPLEMENTED AT THE INSTITUTE TO FOCUS ON CURRENT AND FUTURE CONCERNS OF FEMALE RESEARCHERS WITHIN THE INSTITUTE. ICM IS, FIRST AND FOREMOST, A HUMAN ADVENTURE, A COMMUNITY OF EXPERTS THAT ARE ACTIVELY INVOLVED IN FIGHTING AGAINST NERVOUS SYSTEM DISEASES ON A DAILY BASIS. The goal of the think tank, named XXInitiative and made up of women and men dedicated to promoting the role of women in science, is to come up with and execute effective action to: Researchers, doctors, biologists, pharmacologists, mathematicians, engineers, physicians, programmers, technicians, paramedical staff, support staff… ICM brings together multidisciplinary individuals who work hand in hand. Thanks to close Encourage female scientists and their career collaboration between researchers and doctors, patients benefit from diagnostic and therapeutic innovations more rapidly. Promote access to high-level scientific positions for women ICM’s strength lies in the interaction between experts of different fields and the pooling of their skills to discover treatments as fast as possible. Drive governing bodies and scientific events towards gender parity

“I develop far-reaching translational I work with patients with spinal damage. “I develop innovative instruments for “I am in charge of care management “I develop statistical analysis research projects. I discovered just how The future seems to lie in the ability to tomorrow’s medical world. With the and development in the neurology instruments and help users with the enriching it could be to bring fundamental blend energy and knowledge. ICM is at Dynamo (DYNAmic Models) project, department and am involved in the CENIR MEG-EEG platform. The unique and clinical research together. the heart of the hospital, a couple feet in collaboration with Professor Hampel, University Medical Center’s three-fold side of ICM is that it puts equipment, I decided to join ICM after several years away from the orthopedic and trauma our teams are striving to create numerical mission: care, learning and training, infrastructure and staff under one roof, doing research in a major department I am in charge of. modelling of brain evolution during and research. ICM-A-IHU helped train allowing us to pool resources, build lab. The quality of my work changed This geographical proximity is very Alzheimer’s diseases, in hopes of Nursing and Paramedical Research collaborations, and help innovative drastically, because I now interact with practical: it’s that simple! Given how creating a precise medical instrument, Committee members on how to develop projects come to light. I now work with neurobiologists and pharmacologists complex my schedule is at the hospital, both predictive and personalized. Data a research project, allowing us to win everyone at ICM: researchers, doctors, on a daily basis who bring different it allows me to participate in fundamental comparison between patients and the a national call for projects with the engineers… on projects not only linked approaches to the table. I’m passionate research on the spinal cord developed model will allow teams to personalize Neurosex project. The project will to the MEG-EEG but that also pertain to about this kind of interaction. at ICM. Surgeons and researchers the diagnosis and predict disease implement nursing consultations in sexual functional MRI, spectroscopy and TMS. By bringing their knowledge on are mutually enriching thanks to our progression to put appropriate care health for patients with neurological ICM trusted me to organize a statistics fundamental mechanics with my clinical knowledge and different approaches in place as early as possible and diseases, and it motivated me to do a course with Professoressor Hervé Abdi results, I have the opportunity to develop towards science and progress. It’s implement tailored treatment. This thesis supported financially by ICM-A-IHU. from Dallas University: it was a success, actual translational research projects with exceptional to be able to go from the innovative and interdisciplinary project Thanks to ICM-A-IHU, the department and I hope to get the opportunity quicker progress. ICM is truly unique!” operating room and patient appointments was possible at ICM thanks to the developed a shared scientific culture and again.” to laboratory study of the spinal cord. constant interaction with clinicians opens the door to innovation and research BENEDETTA BODINI, I am absolutely positive that our made possible at the Institute.” for hospital staff. It’s a fantastic way to bring LYDIA YAHIA-CHÉRIF, INSERM NEUROLOGIST interactions will benefit patients.” meaning back into what we do!” RESEARCH ENGINEER STANLEY DURRLEMAN, AND RESEARCHER AT ICM ON THE MEG-EEG PLATFORM PROFESSOR HUGUES INRIA RESEARCH MATHEMATICIAN SANDRINE LEFEBVRE, PASCAL-MOUSSELARD, AT ICM SENIOR HEALTHCARE MANAGER ORTHOPEDIC SURGERY AND IN THE NERVOUS SYSTEM DISEASES TRAUMATOLOGY DEPARTMENT CHIEF DEPARTMENT AT PITIÉ-SALPÊTRIÈRE AT PITIÉ-SALPÊTRIÈRE HOSPITAL HOSPITAL

24 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 25 ICM WOMEN AND MEN ICM BY THE NUMBERS

56 HOSPITAL PRACTITIONERS AND PARAMEDICAL STAFF

135 RESEARCHERS

55 POST-DOCTORAL RESEARCHERS

92 DOCTORAL RESEARCHERS

181 ENGINEERS AND TECHNICIANS

88 ADMINISTRATIVE STAFF

32 DIFFERENT COUNTRIES REPRESENTED SO MUCH HAPPENING AT ICM

Les Ajités, ICM Youth Organization and research projects. The organization aims meeting new people, ICM is a unique Associates, was founded in 2012. at developing communication, interaction opportunity to think differently, open up It organizes all sorts of activities from and collaboration among ICM staff. It is our approach and ways of working, yoga, salsa dancing, Science-Pizza, Happy frequently updated, bringing a strong and to innovate. Working at ICM means Hours to practice for oral presentations internal motivation and forward drive to belonging to something greater: and doctoral and post-doc workshops, an the Institute. For those constantly on the a community dedicated to Neuroscience. opportunity to develop interdisciplinary lookout for new projects and who enjoy

26 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 27 ICM GOVERNANCE AUDIT COMMITTEE BOARD OF DIRECTORS MEMBERS FOUNDING MEMBERS THE SCIENTIFIC ADVISORY Serge WEINBERG BOARD Gérard SAILLANT Gérard SAILLANT, Audit Committee The International Scientific GOVERNANCE FOCUSED ON EFFICIENCY AND FLEXIBILITY Professoressor of othopedic Professoressor of othopedic President Advisory Board (SAB) as- and trauma surgery, President and trauma surgery, Thierry DAMERVAL sists the Board of Directors of ICM President of ICM Deputy Chief Executive Jean TODT of INSERM or Chief Executive on stra- Jean TODT President of the FIA, Jean GLAVANY tegic directions, programs, or scientific strategies for President of the FIA, Vice-President of ICM Former Minister, the Institute. Its members Vice-President of ICM Yves AGID Representative of the Honorary Professoressor of Hautes-Pyrénées are top international neu- neurology and neuroscience roscience experts. Every COLLEGE OF FOUNDERS Jean-Pierre MARTEL Luc BESSON Lawyer, Founding five years, ICM is assessed, Serge WEINBERG Director Member of ICM as a Mixed Research Unit Jean GLAVANY Louis CAMILLERI (UMR), on the quality of Jean-Pierre MARTEL President of Altria its research, its organiza- Gérard SAILLANT Jean GLAVANY COORDINATION OF tion, strategy, and five-year Jean TODT Former Minister, Representative FOUNDATION AND scientific plan. ICM’s governance is based on a strong of the Hautes-Pyrénées PUBLIC PARTNER RELA- Research projects are as- TIONSHIPS COMMITTEE partnership between the public and COLLEGE OF QUALIFIED Maurice LÉVY sessed by the SAB, with the mission of advising the private sectors, as illustrated by its PERSONS President of the Board of Publi- Gérard SAILLANT Institute and helping it de- board members and governing bodies. cis Group, Co-President of the Professoressor of othope- Pierre CORVOL Friends of ICM Committee fine its overall approach. They ensure that structures and dic and trauma surgery, Collège de France Olivier LYON-CAEN Following a period of President of ICM resources properly match scientific Richard FRACKOWIAK discussions, the SAB pro- Professoressor of neurology, Ali FERHI goals. The Executive Committee École Polytechnique Fédérale vides input that is taken former Director of the Nervous Representative of AP-HP de Lausanne into account to build the implements monitoring to ensure System Diseases department Bernard POULAIN Elisabeth TOURNIER-LAS- file for assessment by the efficient management is in place, as THE BOARD OF DIRECTORS at Pitié-Salpêtrière University Representative of CNRS SERVE Medical Center Committee for Assessment well as ongoing evaluation of work Thierry DAMERVAL Université Paris Diderot Jean-Pierre MARTEL of Research and Higher The board of directors manages Institute affairs through its proceed- Representative of done by the teams and their results, Education (HCERES). Lawyer, l’INSERM to guarantee continued excellence. ings. It weighs in on strategic directions presented by the Chief COLLEGE OF EX OFFICIO Max MOSLEY Bruno RIOU Through its Annual Report, ICM is Executive, adopts budgets and approves accounts. “Our challenge is to create MEMBERS Former President of the FIA Representative of UPMC dedicated to providing information Lindsay OWEN-JONES an Institute for Excellence Bernard POULAIN in Research that is an inter- on its mission and results for total The Foundation is governed by a board made up of fifteen members Honorary President of L’Oréal, Representative of the National Honorary President of the AMBASSADORS national leader in Neurosci- transparency in its partnerships. including: Center for Scientific Research Friends of ICM Committee Jean RENO ence”. -5 founding college members; (CNRS) David de ROTHSCHILD Acteur Professor Alexis Brice, -3 members of the college of qualified persons; In March 2011, ICM signed, with Thierry DAMERVAL President of Rothschild & Cie Michèle YEOH Chief Executive of ICM academic partners AP-HP, CNRS, Inserm -4 ex officio members; Representative of the National bank, Actrice Health and Medical Research Michael Shelanski - and UPMC, an agreement which governs -3 members of the college of friends of the foundation. Co-President of the Friends Institute (INSERM) of ICM Committee President the modalities of work in common of Bruno RIOU Michael SCHUMACHER Dimitri Kullman research teams under the direction of The college of founders includes not only the founders themselves, Representative of Pierre et Formula 1 Pilot Gabor Tamas but also members selected by the founding college and renewed by it. ICM general director. This agreement Marie Curie University (UPMC) Serge WEINBERG Peter Brown provides the creation of a Coordination The college of qualified persons includes individuals chosen for their Ali FERHI President of Weinberg Capital Brad Hyman Representative of Assistance Committee (which stem from the competency in the foundation’s field. Partners, ICM Treasurer Stephen Hauser Publique – Hôpitaux de Paris Bill Richardson Executive Board of ICM), whose role The college of ex officio members includes representatives from AP-HP, (AP-HP) Helen Mayberg CNRS, INSERM and Pierre et Marie Curie University. is to make proposals to the Executive FRIENDS OF ICM Christian Buchel The college of friends of the foundation is comprised of individuals Board of ICM on the research strategy COLLEGE OF FRIENDS Arnold Kriegstein appointed by the Circle of Friends of ICM. Lily SAFRA Honorary President, President of the of the Institute. OF THE FOUNDATION Masud Husain philanthropic Edmond J. Safra Foundation In 2016, the Director of ICM was With the exception of founding members, all board members are Michael Heneka Maurice LÉVY Gérard SAILLANT Professoressor of orthopedic surgery appointed General Director of the appointed for a three-year term with one third renewed annually. Jean-Philippe HOTTINGUER and traumatology, President of ICM Their term can be renewed. IHU-A-ICM to ensure both entities David de ROTHSCHILD Jean TODT President of the FIA, Vice-President of ICM benefit from one single governing body Lindsay OWEN-JONES Honorary President of L’Oréal, as their social mission shares numerous The bureau meets at least four times per year at GOVERNMENT COMMISSIONER Honorary President of the Friends of ICM Committee of the President of the Foundation in order to: Maurice LÉVY President of the Board of Directors traits, with a common roadmap. Philippe RITTER of Publicis Group, Co-President of the Friends of ICM Com- The Board of Directors also approved - Make arrangements, acting on authority of the Board of Directors mittee when applicable, to ensure the foundation runs smoothly between the merger of both entities, planned David de ROTHSCHILD President of the Rothschild & Cie board meetings; for 2017. Bank, CoPresident of the Friends of ICM Committee - Manage preparation and monitoring of decisions made by the board Jean-Pierre MARTEL Lawyer of directors. Serge WEINBERG President of Weinberg Capital Partners and ICM Treasurer

28 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 29 MISSION

A key player at the heart of 21st century UNDERSTANDING THE NERVOUS SYSTEM challenges p.32 IMPLIES HAVING A HUMAN SKILL SET AND THE INSTRUMENTAL AND ORGANIZATIONAL What does it mean to do research today? p.34 CAPACITY TO OBTAIN RELEVANT DATA FOR EACH LEVEL OF RESEARCH, TO Cutting-edge research ANALYZE FUNDAMENTAL DATA AND TO Research programs p.36 CORRELATE AND INTEGRATE IT TO GIVE RISE TO A COHERENT VISION, FROM THE Research teams p.40 MOLECULAR AND CELLULAR LEVEL UP TO Overview and publication examples p.44 COGNITIVE AND BEHAVIORAL LEVELS. Synergy p.50 Awards and distinctions p.52

Teaching and training p.54

National and international collaboration p.56

Clinical research Center for Clinical Investigation p.58 Nervous System Diseases Center p.60 Knowledge sharing & innovation Research & Technology Development Office p.62 Living Lab & Findmed p.64 iPEPS-ICM incubator p.66

SUPPORT our mission

State-of-the-art technological platforms p.70

30 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 31 MISSION A GLOBAL CHALLENGE A KEY PLAYER AT THE HEART OF 21ST CENTURY CHALLENGES

NEARLY ONE BILLION INDIVIDUALS WORLDWIDE ARE WHY IS IT TAKING SO LONG TO DEVELOP AFFECTED BY NEUROLOGICAL TREATMENT FOR NERVOUS SYSTEM In Europe, OR PSYCHIATRIC ILLNESS, DISEASES? AND 80% OF THESE There are several reasons. First of A second reason lies in the fact 1 in 8 individuals INDIVIDUALS DO NOT BENEFIT all, the major neurodegenerative that the deign itself of candidate FROM APPROPRIATE OR diseases share a late appearance drugs to treat nervous system is affected by nervous diseases is complicated by the ADEQUATE TREATMENT. THE of clinical symptoms. For exemple, the first signs of “Great Wall of China” that is system illness" CHALLENGE IS HUGE. FOR Parkinson’s disease appear the blood-brain barrier, which YEARS, THE INDUSTRY HAS when over 80% of dopaminergic prevents drugs from passing neurons in the substantia nigra through. The chemical and FACED INCREASING FAILURE have already been destroyed. protein engineering required to RATES IN INNOVATIVE DRUG In the same manner, the brain ensure that a specific therapeutic ICM: A HIGH-LEVEL INSTITUTE FACED WITH EVEN HIGHER STAKES DEVELOPMENT: 15% OF can be flooded with amyloid molecule reaches the appropriate plaques without a patient target cell is colossal. ICM’s defining strength is its constraints often found in research. dedicated to tech solutions, and CANDIDATE DRUGS THAT showing any clinical symptoms The third major obstacle in ability to take into account the The Nervous System Diseases the neuroinformatics project that UNDERGO CLINICAL TESTING of Alzheimer’s yet. Treatment is developing drugs that work is the whole healthcare process rather department opens its doors to aims at implementing instruments administered late in the disease, relevance of new targets. Action than drugs alone. This approach 80,000 patients every year, who to encourage more predictive and ARE PUT ON THE MARKET, so its efficacy is limited due to directed against a certain cellular brings together research, platform have access to the latest treatment quantitative medicine when it YET THIS FIGURE DROPS irreversible damage already target can have completely and expert support, startup breakthroughs and are active comes to diagnosis, prognosis technology and national and TO 7% FOR THE NERVOUS experienced by the brain. One of antagonistic effects from one participants in research. and therapy. the most promising approaches area of the brain to another, international network involvement. Positioned at the crossroads of Finally, the creation of a hospital SYSTEM. ADDITIONALLY, IN to reach very early detection - at increasing the risk of side effects. various fields, ICM asserts a global living lab helps accelerate THIS EXTREMELY COMPLEX the infraclinical stage - of the Finally, lack of knowledge Moreover, success - in particular approach to illness, and is lowering development of shared early- disease consists in multimodal surrounding disease that of the Center for Clinical the barriers separating pharmacy, stage projects with “medtech” FIELD OVER 12 YEARS ARE biomarker research on individuals physiopathology and the Investigation, housed in ICM - was technology and humanities to companies as well as business NEEDED FOR A DRUG TO BE with a high risk of developing inexistence of satisfactory obtained through the creation design integrated healthcare focused on telemedical services. READY VERSUS, FOR EXAMPLE, the disease. These high-risk preclinical modelling leads of a collaborative environment that starts with prevention, One of the main goals is to individuals are those related to to dramatic failures in drug between researchers, doctors and leading up to management of increase the number of French 6.5 YEARS IN THE FIELD OF patients with a genetic form of development. patients. Industry partnerships disabilities, using technology startups in the field by dedicating CARDIOVASCULAR ILLNESS. the disease. between the public and private as a dedicated instrument. This the necessary resources to designing sector at ICM helped accelerate strategy is implemented with functional prototypes approved for and turn discoveries into practical the development of a startup patient use. treatment solutions for clinical accelerator, currently hosting 16 use, while lowering academic businesses, the new living lab

32 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 33 MISSION RESEARCHER WOMEN AND MEN WHO DO IT ALL BEING A RESEARCHER TODAY

Researchers today are women and men who do it all: to recruiting top

talent, building a multidisciplinary and multicultural team and securing

financing. Being a researcher today means solving scientific problems,

sharing results with scientists and the general public while keeping

an eye on research elsewhere around the world. Being a researcher is

motivating, but also very demanding!

For researchers and experts, ICM is the ideal place to come up with new

ideas, nurture broader reflection, and build projects. The diversity of

talent and unique interactions at the Institute enrich the everyday work

of research team. To work on a project together, potential partners need

to be available and the timing has to be just right. Building a suitable

environment is of prime importance.

Scientific research is a long-term endeavor and requires financial,

human, technological and environmental investment. Some research

that may go under the radar could possibly reveal its full potential

on the long term.

34 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 35 MISSION CUTTING-EDGE RESEARCH

RESEARCH PROGRAMS AT THE HEART OF HEALTHCARE

FOCUS 2 : UNDERSTANDING NEURAL INTERACTION NEUROPHYSIOLOGY

erve impulse transmission in the various neural networks is the basis of nervous system activity. It Nrelies on excitability, conduction, and transmission of the nerve impulse generated by each neuron and on network plasticity. Brain and spinal cord neurophysiology, from single cells to the whole network, help understand the principles through which neural activity leads to specific functions that induce normal or abnormal behavior. The study of neural networks is a foundational aspect of therapeutic research for various illnesses: epilepsy, trauma, neurodegenerative illnesses, psychiatric disorders. The goal, on the one hand, is to reach a better understanding 4 RESEARCH PRIORITIES of neural and network physiology to improve disease treatment. On the other hand, it is to better understand the role played by neural activity during development and repair in neurodegenerative illnesses. Surface electrophysiology (transcranial magnetic stimulation) and FOCUS 1 : UNDERSTANDING THE BRAIN’S MAJOR FUNCTIONS intracerebral electrophysiology (deep brain stimulation) in humans are one of ICM’s greatest strengths. They make BEHAVIOR AND COGNITION it possible to treat certain illnesses such as Parkinson’s disease, OCD, essential tremor, to encourage rehabilitation erception, language, motivation, reasoning, emotions, creativity, memory, after a stroke and to monitor severe forms of certain attention, and conscience form the basis of human behavior. To describe diseases such as epilepsy. Pand understand the brain’s major functions, ICM teams rely on experimental methods from the most subtle clinical analysis, electrophysiological testing, to brain imaging. Thanks to this approach, Institute researchers study the relationship between genetics, brain function, and behavior in healthy individuals as well as patients with neuropsychiatric disorders (depression, OCD, trauma, apathy, dementia…) in order to identify new markers of behavior and cognition both normal and abnormal. The goal is to offer diagnostic tools and treatments tailored to each patient.

36 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 37 MISSION CUTTING-EDGE RESEARCH

FOCUS 3 : DECRYPT UNDERLYING CELLULAR AND MOLECULAR MECHANISMS OF BRAIN FUNCTION IN NORMAL AND PATHOLOGICAL CONDITIONS

CELLULAR AND MOLECULAR BIOLOGY

CM teams working in molecular and cellular neuroscience are involved in a collaborative effort to Iunderstand normal brain and spinal cord development as well as the reasons behind dysfunction in the case of aging and neurological illness (neurodegenerative diseases, multiple sclerosis, epilepsy, brain tumors). ICM’s strategy is focused on evaluating the influence of genetics, dissecting the molecular process behind intracellular signalling, understanding the role of various cell types and the complex cell interactions in normal and pathological states. Understanding the molecular and cellular basis of nervous system disorders is key to figuring out what the underlying mechanisms of disease are and to developing new diagnostic and treatment approaches. FOCUS 4 : TRANSFERRING KNOWLEDGE TO IMPROVE PREVENTION AND TREATMENT OF NERVOUS SYSTEM DISEASES

CLINICAL AND TRANSLATIONAL RESEARCH

linical and translational research dedicated to neurological and psychiatric illnesses aims at developing innovative therapies for nervous system diseases. CBy bringing patients, doctors and researchers together in one place, ICM’s goal is to encourage rapid development of treatments for nervous system damage in order to pass it along to patients as early as possible: from treatment identification on simple models in a laboratory setting to clinical trials on patients at the Center for Clinical Investigation at ICM. ICM’s strength also lies in the iPEPS-ICM incubator that creates a pathway between research and resulting real-life medical applications. The implementation of a living lab (UCIL) where patients, developers and healthcare professoressionals meet to generate ideas and apply them is the ultimate link in the chain created to meet patient needs. The goal of this research is to develop instruments that will help with early disease diagnosis and to explore innovative therapeutic options. Therapy means drugs to fight the disease and slow its progress, but it also means medical techniques such as deep brain stimulation to help patient well-being or digital solutions that improve patient independence like smartphone apps, connected devices or therapeutic games.

38 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 39 MISSION RESEARCH TEAMS Alexandra DURR GENEROUS SUPPORT GRANTED BY : GEN-PHYS: NEUROGENETICS Isabelle LEBER ANR - Agence nationale de recherche AND PHYSIOLOGY Suzanne LESAGE FRC - Fondation pour la Recherche Team leader(s) Fanny MOCHEL sur le Cerveau Bertrand FONTAINE Annie SITTLER Institut Universitaire d’Ingénierie Sophie NICOLE 26 TEAMS TACKLING THE NERVOUS Giovanni STEVANIN pour la Santé (IUIS) Hamid ELHACHIMI OCIRP Principal investigators Morwena LATOUCHE Bertrand FONTAINE SYSTEM LESIONS IN 2016 Claire PUJOL ARAMIS: ALGORITHMS, MODELS Sophie NICOLE Caroline NAVA AND METHODS FOR IMAGES AND Cécile DELARASSE Mohamed EL BEHI ICM’S 26 RESEARCH TEAMS WORK HAND IN HAND TO UNDERSTAND NORMAL AND PATHOLOGICAL SIGNALS OF THE HUMAN BRAIN GENEROUS SUPPORT GRANTED BY : Isabelle REBEIX BRAIN FUNCTIONS, TO DIAGNOSE NEUROLOGICAL ILLNESS AS EARLY AS POSSIBLE AND TO IDENTIFY ADRMGNP - Association pour Team leader(s) Laure STROCHLIC le Développement de la Recherche Olivier COLLIOT POSSIBLE TREATMENTS. sur les Maladies Génétiques Didier DORMONT GENEROUS SUPPORT GRANTED BY : Neurologiques et Psychiatriques AFHA - Association Française Principal investigators AFH - Don de l'Hémiplégie Alternante Olivier COLLIOT CELLULAR PHYSIOLOGY OF CORTICAL PICNIC LAB: PHYSIOLOGICAL ALS : CAUSES AND MECHANISMS AHF - Association Huntington France AFM - Association Française Didier DORMONT MICROCIRCUITS INVESTIGATIONS OF CLINICALLY OF MOTOR NEURON DEGENERATION ANR - Agence nationale de recherche contre les Myopathies Stanley DURLEMANN NORMAL AND IMPAIRED COGNITION ANSM - Agence Nationale de Sécurité ARN - Association pour la recherche Team leader(s) : Alberto BACCI Team leader(s) DE VICO FALLANI du Médicament et des Produits de Santé sur les Nicotianées Team leader(s) Séverine BOILLEE Fabrizio DE VICO FALLANI Principal investigators APHP ARSEP – Aide à la recherche Paolo BARTOLOMEO Marie CHUPIN Alberto BACCI Principal investigators ASL - Association Strümpell-Lorrain sur la sclérose en plaques Laurent COHEN Anne BERTRAND Xavier DREVELLE Severine BOILLEE BOLLORE DIM Cerveau et Pensée Manifestations Lionel NACCACHE Damien GALANO Delphine BOHL CEE - Scientifiques Centre Hospitalo-Universitaire Régional Dominique HASBOUN GENEROUS SUPPORT GRANTED BY : Principal investigators Christian LOBSIGER FMR - Fondation Maladies Rares (ex GIS) de Lille Sophie DUPONT ANR - Agence nationale de recherche Paolo BARTOLOMEO Stephanie MILLECAMPS Fondation de l'Avenir CHDI Foundation Yves SAMSON DGCS - Ministère de l'Egalité des Laurent COHEN Danielle SEILHEAN Université Claude Bernard Lyon 1 CSC- Association Connaître Territoires et du Logment François SALACHAS GeNeuro SA Lionel NACCACHE GENEROUS SUPPORT GRANTED BY : ENP -Ecole des Paris Vincent MEININGER les Syndromes Cérébelleux Jacobo SITT ANR - Agence nationale de recherche Ile de France DIM Cerveau et Pensée Manifestations Scientifiques APHP SOCIAL AND AFFECTIVE NEUROSCIENCE FRM - Fondation pour la Recherche GENEROUS SUPPORT GRANTED BY : GENEROUS SUPPORT GRANTED BY : Elisabeth Badinter CEE - European Commission Médicale ANR - Agence nationale de recherche ACE - Association pour l'étude Team leader(s) ENP -Ecole des neurosciences Tous les donateurs du projet DYNAMO CEE - European Commission de la culture d'embryon Nathalie GEORGE AFM - Association Française Paris Ile de France CELLULAR AND MOLECULAR APPROACHES ENP -Ecole des neurosciences Philippe FOSSATI F-CRIN Paris Ile de France contre les Myopathies FRONTLAB: FRONTAL SYSTEMS, FUNCTIONS FOR MYELIN REPAIR FDF - Fondation de France Principal investigators Fondation Voir et Entendre ALS association AND DYSFUNCTIONS FMR - Fondation Maladies Rares (ex GIS) Nathalie GEORGE Team leader(s) FRM - Fondation pour la recherche ANR - Agence nationale de recherche Fondation Carlo Besta Team leader(s) Philippe FOSSATI Anne BARON VAN EVERCOOREN médicale ANSES - Agence Nationale de Sécurité Fondation Edmond J. Safra Bruno DUBOIS Stephanie DUBAL Brahim NAIT OUMESMAR LesHanot Haim Foundation Sanitaire de l'Alimentaion Fondation Jacques et Gloria Gossweiler Richard LEVY Bruno MILLET McDonnell Foundation de l'Envionnement et du travail Principal investigators Fondazion Istituto Neurologico Carlo Sylvain Héfès ARMC - Aide à la recherche Principal investigators Anne BARON Besta GENEROUS SUPPORT GRANTED BY : des Maladies du Cerveau Bruno DUBOIS Brahim NAIT OUMESMAR France Parkinson ANR - Agence nationale de recherche ARSLA - Association pour la Recherche Richard LEVY Lamia BOUSLAMA GENETICS AND PHYSIOPATHOLOGY FRM - Fondation pour la recherche DIM Cerveau et Pensée Petits et Moyens sur la Sclérose Latérale Amyotrophique Benedicte BATRANCOURT Violetta ZUJOVIC OF EPILEPSY médicale Equipements et autres maladies du motoneurone Raffaella MIGLIACCIO HUNTINGTON ESPOIR OUEST Fondation des Geules Cassées Team leader(s) Fondation Thierry Latran Michel THIEBAUT GENEROUS SUPPORT GRANTED BY : INSERM -COSSEC Fondation Pierre Deniker Stéphanie BAULAC Institut Pasteur Antoni VALEROCABRE AFM - Association Française contre ULM - University Hospital of ULM FRM - Fondation pour la recherche Eric LEGUERN Medday Emmanuelle VOLLE les Myopathies VERUM FONDATION médicale Amélie FAYET Harald HAMPEL ANR - Agence nationale de recherche Principal investigators Ultragenyx Pharmaceutical Inc. Purdue University North Central Edith DEBOUDE Marc TEICHMAN ARSEP - Aide à la Recherche Stephanie BAULAC sur la Sclérose en Plaques Eric LEGUERN EXCITABILITY AND DYNAMICS GENEROUS SUPPORT GRANTED BY : ALZHEIMER’S DISEASE, PRION DISEASES ELA research foundation Christel DEPIENNE MOLECULAR BASIS, PHYSIOPATHOLOGY OF NEURONAL ASSEMBLIES Association PSP France ENP -Ecole des neurosciences AND TREATMENT OF NEURODEGENERATIVE Team leader(s) Sarah WECKHUYSEN ANR - Agence nationale de recherche Paris Ile de France Stéphane HAIK DISEASES Team leader(s) APHP Marie-Claude POTIER Fondation Jérôme Lejeune GENEROUS SUPPORT GRANTED BY : Stéphane CHARPIER Team leader(s) CEE - European Commission FRC - FEDERATION POUR Ambassade de France au japon Principal investigators DIM Cerveau et Pensée Petits LA RECHERCHE SUR LE CERVEAU ANR - Agence nationale de recherche Alexis BRICE Principal investigators et Moyens Equipements NMSS - national Multiple Sclerosis Society APHP Stéphane CHARPIER Stephane HAIK Principal investigators FRM - Fondation pour la recherche OCIRP CEE - European Commission Michel LE VAN QUYEN Marie-Claude POTIER Alexis BRICE médicale UPMC FDF - Fondation de France Severine MAHON Benoit DELATOUR Olga CORTI NIH - National Institutes of Health FMR - Fondation Maladies Rares (ex GIS) Vincent NAVARRO Nicolas BIZAT Jean-Christophe CORVOL Edouard et Martine de ROYERE Mario CHAVEZ Charles DUYCKAERTS FRC - FEDERATION POUR Frederic DARIOS Stéphane EPELBAUM LA RECHERCHE SUR LE CERVEAU Christel DEPIENNE

40 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 41 MISSION RESEARCH TEAMS

Serge MARTY MJFOX - THE MICHAEL J FOX ABNORMAL MOVEMENTS AND BASAL Marc DAVENNE Sébastien BOURET OLIGODENDROCYTE DEVELOPMENT Jean-Philippe BRANDEL FOUNDATION GANGLIA: PHYSIOPATHOLOGY Anne DESMAZIERES Jean DAUNIZEAU AND NEUROVASCULAR INTERACTIONS Air Liquide Santé International AND EXPERIMENTAL THERAPY Nathalie SOL-FOULON Principal investigators Team leader(s) GENEROUS SUPPORT GRANTED BY : Mathias PESSIGLIONE ANR - Agence nationale de recherche Team leader(s) GENEROUS SUPPORT GRANTED BY : Jean-Leon THOMAS (Boris ZALC) Sebastien BOURET CJD Foundation Stéphane LEHERICY ANR - Agence nationale de recherche Principal investigators MOLECULAR AND CELLULAR MECHANISMS Jean DAUNIZEAU France Alzheimer Marie VIDAILHET ARSEP - Aide à la Recherche sur la OF GLIOMA GENESIS Jean-Leon THOMAS GIS - IBISA Sclérose en Plaques Principal investigators GENEROUS SUPPORT GRANTED BY : Boris ZALC Institut Pasteur Team leader(s) FDF - Fondation de France Marie VIDAILHET Campus France - Campus Prestige Charles CALVO InVs - Institut de veille sanitaire Emmanuelle HUILLARD FRM - Fondation pour la recherche Stephane LEHERICY CEE - European Commission Carlos PARRAS LECMA - Ligue Européenne médicale Michel MALLAT Principal investigators Andreas HARTMANN DIM Cerveau et Pensée Manifestations contre la Maladie Alzheimer INSERM - interface Emmanuelle HUILLARD Pierre POUGET Scientifiques LFB Biomédicaments MSIF - Multiple Sclerosis International GENEROUS SUPPORT GRANTED BY : Isabelle LE ROUX Charlotte ROSSO ENP -Ecole des neurosciences Les Laboratoires Servier Federation ANR - Agence nationale de recherche Emmanuel ROZE Paris Ile de France Sanofi-Aventis Recherche NMSS - national Multiple Sclerosis ANSES - Agence Nationale de Sécurité GENEROUS SUPPORT GRANTED BY : Isabelle ARNULF FRM - Fondation pour la Recherche et Développement Society Sanitaire de l'Alimentaion de Cancéropôle Ile-de-France Bertrand DEGOS Médicale Medday Fondation MARIE-ANGE BOUVET l'Envionnement et du travail CEE - European Commission Sabine MEUNIER Ministère Français des Affaires LABRUYERE ARSEP – Aide à la recherche INSERM - ATIP AVENIR Alexandra PETIET Etrangères sur la sclérose en plaques La Ligue nationale contre le Cancer Sophie RIVAUD-PECHOUX Claude FELIX NEURAL DEVELOPMENT NMSS - national Multiple Sclerosis GENEROUS SUPPORT GRANTED BY : BEHAVIOR, EMOTION, Society Team leader(s) AFGST / FRM - Fondation pour la AND BASAL GANGLIA Bassem HASSAN TREATMENT OF AMYOTROPHIC LATERAL BIOTECHNOLOGY AND BIOTHERAPY recherche médicale SCLEROSIS: FROM GENETICS TO ZEBRAFISH AFHA - Association Française Team leader(s) Principal investigators Team leader(s) PROBING DYNAMIC SENSORY-MOTOR Luc MALLET Bassem HASSAN de l'Hémiplégie Alternante Philippe RAVASSARD Team leader(s) INTEGRATION IN SPINAL CIRCUITS ANR - Agence nationale de recherche Jérôme YELNIK Edor KABASHI Principal investigators GENEROUS SUPPORT GRANTED BY : APHP Principal investigators Team leader(s) Principal investigators Philippe RAVASSARD The Family Foundation APTES - Association des personnes Luc MALLET Claire WYART Edor KABASHI Rolando MELONI concernées par le tremblement essentiel Jérôme YELNIK Sorana CIURA Helene CHEVAL Principal investigators Campus France - Campus Prestige Eric BURGUIERE ENS - Ecole Normale Supérieur Claire WYART EXPERIMENTAL THERAPY IN PARKINSON’S Karim NDIAYE GENEROUS SUPPORT GRANTED BY : GENEROUS SUPPORT GRANTED BY : Fondation BETTENCOURT SCHUELLER Pierre-Luc BARDET DISEASE AFM - Association Française contre CEE - European Commission Hugues PASCAL MOUSSELARD Fondation NRJ GENEROUS SUPPORT GRANTED BY : les Myopathies FMR - Fondation Maladies Rares Team leader(s) Fonds PATRICK DE BROU DE LAURIERE ANR - Agence nationale de recherche ANR - Agence nationale de recherche (ex GIS) GENEROUS SUPPORT GRANTED BY : Etienne HIRSCH France Parkinson ARS Ile de France CEE - European Commission Fondation E. J. SAFRA CEE - European Commission INSERM Christian POQUET Principal investigators FRC - Féderation pour la Recherche Les Laboratoires Servier EMBO Institut de Recherche sur la Moelle Fondation de l'avenir Etienne HIRSCH sur le Cerveau ENP -Ecole des neurosciences Epinière et l'Encéphale (IRME) Fondation Fondamental Stephane HUNOT FRM - Fondation pour la recherche Paris Ile de France MDSD France FRM - Fondation pour la recherche Patrick MICHEL médicale FRM - Fondation pour la recherche PSP médicale EXPERIMENTAL NEURO-ONCOLOGY Marie-Laure WELTER Anavex Life Sciences Corp. médicale Quintiles Benefit France Fondation Philippe et Maria Halphen Team leader(s) Fondation MICHELIN David GRABLI Fondation EDF Marc SANSON HFSPO- The Human Frontier Science Rita RAISMAN Fonds de dotation PIERRE BERGE Annie LANNUZEL Program Organization EXPERIMENTAL NEUROSURGERY Fondation AREVA Principal investigators Chantal FRANCOIS CORTEX AND EPILEPSY RIF - Région Ile de France Edouard et Martine de ROYERE Marc SANSON Team leader(s) RTRA - ENP ORKYN' Team leader(s) Jean-Yves DELATTRE GENEROUS SUPPORT GRANTED BY : Brian LAU Institut de recherches internationales Richard MILES Michel KALAMARIDES PSP Principal investigators Servier Khe HOANG-XUAN ANR - Agence nationale de recherche Principal investigators Brian LAU Ahmed IDBAIH BPI France financement Richard MILES Carine KARACHI CEE - European Commission Desdemona FRICKER

CR IDF MECHANISMS OF MYELINATION GENEROUS SUPPORT GRANTED BY : GENEROUS SUPPORT GRANTED BY : APHP FRC - FEDERATION POUR AND REMYELINATION IN THE CNS GENEROUS SUPPORT GRANTED BY : ANR - Agence nationale de recherche Cancéropôle Ile-de-France LA RECHERCHE SUR LE CERVEAU CEE - European Commission CEE - European Commission Team leader(s) Fondation ARC pour la recherche FRM - Fondation pour la Recherche ANR - Agence nationale de recherche France Parkinson Catherine LUBETZKI sur le cancer Médicale Simons Foundation Bruno STANKOFF Institut national du cancer (INCa) IETF - International Essential Tremor Jean-Louis DUFLOUX MOTIVATION, CERVEAU La Ligue nationale contre le Cancer Foundation Principal investigators ET COMPORTEMENT Plan Cancer Catherine LUBETZKI Transgene Team leader(s) Bruno STANKOFF Gecko Biomedical Mathias PESSIGLIONE Eli Lilly and Company

42 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 43 MISSION OVERVIEW AND PUBLICATION EXAMPLES 2016, ALS Highlighting similarities between ALS and hereditary spastic paraplegia to A YEAR OF BREAKTHROUGHS allow clinicians to improve diagnosis. From the team led by Alexis Brice Motor neuron degeneration in spastic paraplegia 11 mimics amyotrophic lateral sclerosis lesions. Denora PS, Smets K, Zolfanelli F, Ceuterick-de Groote C, Casali C, Deconinck T, Sieben A, Gonzales M, Zuchner S, Darios F, Peeters D, Brice A, Malandrini A, De Jonghe P, Santorelli FM, Stevanin G, Martin JJ, El Hachimi ON THE RESEARCH SIDE KH. Brain. 2016 Jun;139(Pt 6):1723-34.

EPILEPSY Proof in “real time” of a process involved in the interruption of conscious perception during absence seizures. From the team led by Stéphane Charpier ALZHEIMER’S Integrative properties and transfer function of cortical neurons initiating absence seizures in a rat genetic model. Williams Mark S., Altwegg-Boussac Tristan, Chavez Mario, Lecas Sarah, Mahon Séverine and Hope for early patient care through discovery of brain lesions due to the Charpier Stéphane. The Journal of Physiology, June 17, 2016, 594(18):1-19 illness 20 years prior to onset. By Harald Hampel part of the team led by Bruno Dubois Jansen W.J. et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta- COGNITION analysis. Jama, The Journal of the American Medical Association, 19 mai 2015; 313(19):1924-38 The more tired we feel due to intense work, the more impulsive we get during financial decision-making. PARKINSON’S Neural mechanisms underlying the impact of daylong cognitive work on economic decisions. Development of a new molecule involved in the disease. Bastien Blain, Guillaume Hollard, and Mathias Pessiglione. PNAS, 2016. From the team led by Etienne Hirsch New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular BRAIN ORGANIZATION and Animal Parkinson Disease Models. Gael Le Douaron, Laurent Ferrié, Julia E. Sepulveda-Diaz, Majid Decoding the frontal lobe’s architectural organization. Amar, Abha Harfouche, Blandine Séon-Méniel, Rita Raisman-Vozari, Patrick P. Michel & Bruno Figadère. By Michel Thiebaut de Schotten from the team led by Richard Lévy J. Med. Chem. 14 juillet 2016, 59(13):6169-86 and Bruno Dubois Rostro-caudal architecture of the frontal lobes in humans. Michel Thiebaut de Schotten, Marika Urbanski, AMYOTROPHIC LATERAL SCLEROSIS, ALS Benedicte Batrancourt, RichardLevy, Bruno Dubois, Leonardo Cerliani, Emmanuelle Volle. Cerebral Cortex Discovery of a new mechanism. (2016). From the team led by Edor Kabashi THE MOST PREVALENT GENETIC CAUSE OF ALS-FTD, C9ORF72 SYNERGIZES THE TOXICITY OF BRAIN DEVELOPMENT ATXN2 INTERMEDIATE POLYGLUTAMINE REPEATS THROUGH THE AUTOPHAGY PATHWAY. Ciura Discovery of a new process. S, Sellier C, Campanari ML, Charlet-Berguerand N, Kabashi E. Autophagy. 2016 Aug. Loss of C9ORF72 From the team led by Bassem Hassan impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates death. Sellier C, Campanari ML, Julie Corbier C, Gaucherot A, Kolb-Cheynel I, Oulad-Abdelghani M, Neurogenesis, Cell, Xiao-Jiang Quan et al. 28 janvier 2016, 164(3): 460-75. Ruffenach F, Page A, Ciura S, Kabashi E, Charlet-Berguerand N. EMBO J. 2016 Jun.

44 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 45 MISSION OVERVIEW AND PUBLICATION EXAMPLES

ON THE CLINICAL SIDE

RARE DISEASES ALZHEIMER’S Highlighting the role of protein calpain 1 in ataxia, its neuroprotective An imaging study coordinated by Marie Sarazin, is the first to highlight activity and key role in brain development and . the early protective role of the brain’s immune cells Defects in the CAPN1gene result in alterations in cerebellar development and in cerebellar ataxia in Early and protective microglial activation in Alzheimer’s disease: a prospective study using mice and humans. Yubin Wang et al., Cell Reports, 28 juin 2016, 16 (1): 79-91. 18F-DPA-714 PET imaging. Hamelin L, Lagarde J, Dorothée G, Leroy C, Labit M, Comley RA, de Souza LC, Corne H, Dauphinot L, Bertoux M, Dubois B, Gervais P, Colliot O, Potier MC, Bottlaender M, GILLES DE LA TOURETTE SYNDROME Sarazin M; Clinical IMABio3 team. Brain. 2016 Apr; 139(Pt 4):1252-64. Decoding the mechanisms leading to tic appearance and persistence. From the team led by Marie Vidailhet and Stéphane Lehéricy PARKINSON’S Enhanced habit formation in Gilles de la Tourette syndrome. Delorme C, Salvador A, Valabrègue R, Discovery of new gene VPS13C in an early form of the disease that Roze E, Palminteri S, Vidailhet M, de Wit S, Robbins T, Hartmann A, Worbe Y. Brain. 2016 Feb;139(Pt may support implementation of a diagnostic instrument 2):605-15. from the team led by Alexis Brice Suzanne Lesage et al., Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes SPINAL CORD TRAUMA Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy, American Journal of Renewed hope with the identification of new movement-regulating Human Genetics, Mars 2016, 98(3): 500-513. neurons. From the team led by Claire Wyart PARKINSON’S CSF-contacting neurons regulate locomotion by relaying mechanical stimuli to spinal circuits. Urs Relationship between the brain stem and cardiac disorders highlighted Lucas Böhm et al. Nat Commun. Nature Communication, 2016 Mar 7 thanks to cutting-edge imaging. From the team led by Stéphane Lehéricy and Marie Vidailhet MEMORY Medulla oblongata damage and cardiac autonomic dysfunction in Parkinson disease. Pyatigorskaya Slow-wave sleep may play a part in memory consolidation when the N, Mongin M, Valabregue R, Yahia-Cherif L, Ewenczyk C, Poupon C, Debellemaniere E, Vidailhet M, brain replays what it experienced the previous day. Arnulf I, Lehéricy S. Neurology. 2016 Dec 13;87(24):2540-2545. From the team led by Stéphane Charpier High-frequency oscillations […] during the wake-sleep cycle. Le Van Quyen M, Muller LE, Telenczuk B, PARKINSON’S Halgren E, Cash S, Hatsopoulos NG, Dehghani N, Destexhe A. Proc Natl Acad Sci U S A. 2016 Aug 16. Markers identified to monitor and predict disease progression. From the team led by Marie Vidailhet and Stéphane Lehéricy Ehrminger M. et al. The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder, Brain, avril 2016 ; 139 (4):1180-8

MULTIPLE SCLEROSIS Cutting-edge technique developed to measure disease progression that would allow tailored treatment for each patient. From Benedetta Bodini part of the team led by Bruno Stankoff and Catherine Lubetzki Dynamic imaging of individual remyelination professoriles in multiple sclerosis. Bodini B, Veronese M, García-Lorenzo D, Battaglini M, Poirion E, Chardain A, Freeman L, Louapre C, Tchikviladze M, Papeix C, Dollé F, Zalc B, Lubetzki C, Bottlaender M, Turkheimer F, Stankoff B. Ann Neurol. 2016 Feb Bodini B. et al, Benzothiazole and stilbene derivatives as promising PET myelin radiotracers for multiple sclerosis, Annals of Neurology, 21 avril 2016.

46 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 47 MISSION OVERVIEW AND PUBLICATION EXAMPLES

ON THE START-UP SIDE

TUMORS EPILEPSY Hope for tailored treatment of a certain type of cancer with Smart connected clothing to diagnose epilepsy. glioblastomas that target oncogene MDM2. Bioserenity, managed by Pierre-Yves Frouin, developed the From the team led by Marc Sanson Neuronaute, a medical device already in use in 30 public hospitals Verreault M.et al. Preclinical efficacy of the MDM2 inhibitor RG7112 in MDM2 amplified and TP53 wild- (CE-certified) type glioblastomas. Clin Cancer Res. Mars 2016, 22(5) : 1185-96 FOR BRAIN TUMORS, ULTRASOUND TO INCREASE EPILEPSY TREATMENT DIFFUSION New drug to treat focal seizures. with the “SonoCloud®” ultrasound device developed by CarThera From Michel Baulac in the team led by Stéphanie Baulac and Eric Leguern By CarThera Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine Clinical trial of blood-brain barrier disruption by pulsed ultrasound. in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Alexandre Carpentier and al. Science Translational Medicine, 15 Jun 2016 Baulac M, Rosenow F, Toledo M, Terada K, Li T, De Backer M, Werhahn KJ, Brock M. Lancet Neurol. 2017 Jan;16(1):43-54. PARKINSON’S : Helping patient rehabilitation with a video game, TOAP RUN, with proven efficacy in reducing walking and balance DOWN SYNDROME disorders A natural compound found in green tea improves patient cognitive skills. By Marie-Laure Welter and Pierre Foulon, Brain e-novation From the team led by Marie-Claude Potier and Stéphane Haïk Safety and efficacy of cognitive training plus epigallocatechin-3-gallate for cognitive improvement in MULTIPLE SCLEROSIS young adults with Down’s syndrome (TESDAD): a double-blind, randomised controlled, phase 2 trial. A mobile app for patient evaluation and monitoring at home to Rafael de la Torre et al. The Lancet Neurology, juillet 2016, 15(8): 801-810. provide better care By Ad Scientiam RARE DISEASES A drug with proven efficacy against myoclonic dystonia. From Emmanuel Flamand-Roze in the team led by Marie Vidhaillet and Stéphane Lehéricy A randomized, controlled, double-blind, crossover trial of zonisamide in myoclonus-dystonia. Hainque E et al. Neurology. 2016 May 3;86(18):1729-35

PRIMARY PROGRESSIVE APHASIA A pretherapeutic study shows beneficial effects of direct current transcranial stimulation. From Marc Teichmann and Antoni Valero-Cabré in the team led by Richard Lévy and Bruno Dubois Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia. Teichmann M, Lesoil C, Godard J, Vernet M, Bertrand A, Levy R, Dubois B, Lemoine L, Truong DQ, Bikson M, Kas A, Valero-Cabré A. Ann Neurol. 2016 Sep 19.

48 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 49 MISSION SYNERGY ICM: REVOLUTIONARY, OPEN RESEARCH

AN AMBITIOUS RESEARCH PROGRAM: “BIG BRAIN THEORY”

Ambitious research projects at the frontier of various fields were implemented with the Big Brain Theory program. This call for internal transversal projects aims at encouraging innovative, original, and high-risk initiatives thanks RESEARCH TEAMS ARE INDEPENDENT, FULLY LINKED TO ONE ANOTHER THROUGH to collaborations between the various teams and platforms within the Institute. 15 very promising initiatives TRANSVERSAL RESEARCH PROGRAMS THAT ENCOURAGE POOLING OF SKILLS. were selected and financially supported to explore new research directions. In order to remain competitive and FUNDAMENTAL, CLINICAL AND TRANSLATIONAL RESEARCH COEXIST TO HELP DISCOVER produce high-level research, ICM encourages risk-taking and breakthrough innovation. NEW TREATMENTS AS QUICKLY AS POSSIBLE AND MAKE THEM AVAILABLE FOR PATIENTS.

FUNDAMENTAL RESEARCH LncPD : Discovering new, unexplored DNA areas involved in Parkinson’s disease. 5 FOUNDATIONAL VALUES FOR OUR INSTITUTE, A BREAKTHROUGH ACCELERATOR MOCONET : Researching cortical networks in experimental models of Down syndrome. CLINICAL RESEARCH DIEP : Researching the impact of D2HG, a molecule produced by certain tumors, on the modulation of neighboring immune cell modulation. TRANSLATIONAL RESEARCH DYNAMO : Modeling Alzheimer’s disease progression to improve diagnosis and treatment. A back-and-forth between fundamental and clinical research. It helps patients have MS-BIO-PROGRESS : Designing an innovative instrument to evaluate multiple sclerosis progression. faster access to innovations in diagnosis and therapy. This is the foundation of all LUCID DREAM : Researching lucid dreams to understand gesture sequence learning and automation. research carried out at ICM. TECHNOLOGY AND METHODOLOGY MULTIDISCIPLINARY RESEARCH NG2DB2D – Next-Generation NeuroGenomics DataBases and Big Data : Creating a clinico-genetic database Researchers, doctors, biologists, pharmacologists, mathematicians, engineers, to understand complex pathologies. physicians, IT specialists… ICM brings together multidisciplinary individuals that work closely together. CLINICAL AND FUNDAMENTAL RESEARCH COG_BLIND : Decoding information in the visual cortex of patients with congenital blindness. TRANSVERSAL RESEARCH BIGPARK : Identifying new genes involved in Parkinson’s disease to develop new treatment A breakthrough in one illness can lead to discoveries in others, which is why ICM opportunities. encourages open research with transversal projects (neuroimmunology, for example). iTargetOPC : Targeting oligodendrocyte precursors, cells responsible for myelin sheath development in the central nervous system, as potential treatment for glioblastoma. INNOVATIVE RESEARCH LIBERATE : Understanding the evolution of communication between various cortical areas in normal With incubated startups that develop treatments with researchers, ICM displays and pathological aging. its uniqueness and desire to explore all types of innovation (patents, industry partnerships, living lab…). FUNDAMENTAL RESEARCH, TECHNOLOGICAL AND METHODOLOGICAL

ATTRACTIVE RESEARCH DEVELOPMENT MAXIMS : Verifying the specificity of MRI biomarkers in detecting brain lesions. The Institute is internationally attractive thanks to its scientific reputation and ACTIMYEL : Role played by neural activity in (re)-myelination control. impact in translational research. Resources are available for researchers (platform quality platforms), as well as high-level scientific interactions, independence when it comes to combined direction, and encouraging risk-taking. ICM collaborated with FUNDAMENTAL RESEARCH, CLINICAL RESEARCH AND TECHNOLOGICAL AND internationally-renowned research centers and attracts talented young researchers from around the world: 30% are from another country. METHODOLOGICAL DEVELOPMENT ISIS : Understanding the underlying mechanisms of reduced oxygen supply to the brain.

50 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 51 MISSION AWARDS AND DISTINCTIONS - FOCUS -

MAJOR SCIENTIFIC AWARDS WON EUROPEAN RESEARCH COUNCIL GRANT: BY OUR RESEARCHERS CLOSE TO 10 YEARS OF EXCELLENCE

OUR RESEARCHERS CHANNEL THE SPIRIT OF CHARCOT, MAKING HIS VALUES THEIR OWN. ERC Grants are prestigious awards hailing from a high-level European research program that aims at supporting talented researchers with ambitious and innovative scientific projects. These grants were implemented in 2007 with the Lisbon Treaty EDOR KABASHI BENEDETTA BODINI and founding of the ERC, and have since supported over 7,000 projects and over Neurologist at Pitié-Salpêtrière Hospital Leader of team “Treatment of Amyotro- 50,000 researchers for a total budget of nearly 12 billion euros. ERC grants are and Inserm researcher in the “Central phic lateral sclerosis: from genetics to awarded in very diverse research fields, from mathematics to social science and nervous system myelination mechanisms” zebrafish” at ICM humanities, life science or physics. team at ICM PAULO GONTIJO INTERNATIONAL MEDICINE MARIE-ANGE BOUVET-LABRUYÈRE AWARD AWARD for his research on development for the development of a new imaging of new models and treatment options in technique for multiple sclerosis Amyotrophic Lateral Sclerosis (ALS). > Publication with Bruno Stankoff, team leader at ICM, recognized as one of the BASSEM HASSAN 5 best publications of 2016 on multiple Leader of team “Neural Development” sclerosis by Lancet Neurology at ICM IN 2016, 3 ICM RESEARCHERS WERE AWARDED A GRANT PAUL G. ALLEN FOUNDATION LIONEL NACCACHE “DISTINGUISHED INVESTIGATOR” AWARD TO SUPPORT THEIR RESEARCH. University professoressor, hospital practi- for his work on the frontier of neural tioner, Clinical Neurophysiology Depart- network and behavioral development ment chief at Pitié-Salpêtrière University Medical Center in Paris and team leader at ICM PHILIPPE FOSSATI Psychiatry Professoressor at Pitié Salpê- LAMONICA AWARD trière Hospital and Pierre et Marie Curie in Neurology for his work on University, “Study of emotions and social consciousness interactions” team leader at ICM STANLEY DURRLEMAN STÉPHANIE BAULAC EDOR KABASHI 2016 HALPHEN PRIZE FROM THE PHILIPPE LUCE DAUPHINOT ERC « STARTING GRANT » ERC « CONSOLIDATOR GRANT » ERC « CONSOLIDATOR GRANT » AND MARIA HALPHEN FOUNDATION, for his CNRS Engineer in the team led work on depression by Stéphane Haïk and Marie-Claude Expert in mathematical modelling of Expert in epilepsy genetics, Expert in genetics of amyotrophic Potier at ICM data, INRIA researcher co-manager of the “Epilepsy lateral sclerosis, leader of team CLAIRE WYART part of the ARAMIS team at ICM genetics” team at ICM “Treatment of Amyotrophic lateral CNRS CRISTAL MEDAL Leader of team “Probing dynamic sclerosis: from genetics to zebrafish” for her work on single cells sensory-motor integration in spinal Project: Modelling the brain to Project: Understanding the spectrum circuits” at ICM diagnose and treat neurodegenerative of severity in familial focal seizures Project: Research on Amyotrophic CHRISTIANE SCHREIWEIS illness lateral sclerosis in Zebrafish to identify FENS-KAVLI SCHOLARS 2016 by the Researcher in Luc Mallet’s team, on Hopes to: Verify an initial experimental new treatment opportunities Federation of European Neuroscience “Behavior, emotion and basal ganglia” Hopes to: Design numerical models model for the pathology; Decode the Societies and the Kavli Foundation of the brain showing the effect of processes involved in epilepsy linked Hopes to: Identify new molecules L’ORÉAL-UNESCO GRANT as part of EMBO YOUNG INVESTIGATOR PROGRAM neurodegenerative diseases on brain to the mTOR pathway; and Consider to fight ALS. the l’Oréal-UNESCO “For Women and NEW-YORK STEM CELL FOUNDATION structure, function and metabolism; new treatment opportunities. Science” program, for her research using (NYSCF) ROBERTSON AWARD Use models to implement early innovative methods on repetitive diagnosis and reliable prognosis. behavior, as observed in OCD and Gilles de la Tourette Syndrome.

52 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 53 MISSION TEACHING AND TRAINING PROMOTING CLINICAL A CROSS-DISCIPLINARY RESEARCH APPROACH

THE MOVE SUMMER SCHOOL : BRAIN TO MARKET The Move is a unique program designed for medical “The Brain to Market” summer school is a yearly PASSING ON KNOWLEDGE students by Professoressor Emmanuel Roze, researcher program that combines translational neuroscience and clinician. The Move is an innovative learning and entrepreneurial training through intensive LEARNING AND TRAINING AT THE HEART OF THE INSTITUTE’S MISSION program by simulation that uses miming to teach training to foster new projects, new initiatives and medical students neurological semiology, meaning new ways of approaching neurological illnesses. the clinical expression of neurological illnesses. The The 2016 thematic was epilepsy, with 50 national DEVELOPING CUTTING-EDGE RESEARCH IS DEEPLY LINKED TO SHARING KNOWLEDGE AND FOSTERING NEW program, developed on a national and international and international participants. level, is a remarkable example of innovation in COLLABORATIONS. TO PASS ON AND SHARE KNOWLEDGE ON A NATIONAL AND INTERNATIONAL LEVEL, education. IN COLLABORATION WITH PIERRE AND MARIE CURIE UNIVERSITY, WE IMPLEMENTED AMBITIOUS SEMINAR POST-DOCTORAL PROGRAM Attracting post-doctoral researchers with a PROGRAMS, SUMMER SCHOOLS, AS WELL AS STUDENT AND CLINICIAN EXCHANGES WITH PRESTIGIOUS CLINICIAN EXCHANGE PROGRAM degree in other fields than neuroscience such as A clinician exchange program with Yale, within the INTERNATIONAL INSTITUTIONS. THANKS TO THE IHU PROGRAM AWARDED TO ICM, LEARNING AND TRAINING mathematics, IT, healthcare economics… to apply Neurology department at Pitié Salpêtrière Hospital, ACTIVITIES IN PLACE SINCE 2013 HAVE BECOME A PRIORITY. their knowledge to a specific topic. allows clinicians to learn how our departments work and how we work.

PROGRAM FOR PARAMEDICAL STAFF A program designed for paramedical staff in PROMOTING SCIENCE partnership with the Public Health and Nursing School to develop innovative paramedical research projects.

STUDENT FELLOWSHIPS PROGRAM The “Student fellowship” program is a short- WHAT’S NEXT? term exchange program for Master’s or Doctoral students to help share the expertise of international MAINTAINING AND DEVELOPING CURRENT PROGRAMS. institutions (Massachusetts Institute of Technology, Florey Institute of Neuroscience and Mental Health) and create opportunities for potential collaboration. CREATING AN INTERNATIONAL MASTER’S DEGREE FOCUSED ON NEURODEGENERATIVE ILLNESSES IN RELATIONSHIP WORKSHOP CALL FOR PROJECTS This call for projects is dedicated to ICM “EDUCATION IS AN ESSENTIAL WITH PIERRE ET MARIE CURIE – . researchers and clinicians, to organize international PATHWAY FOR ICM, TO GENERATE seminars within the institute and promote their skills and expertise among their peers to foster AMBITIONS, DEVELOP NEW IMPLEMENTING AN INTRODUCTION TO RESEARCH collaboration. 2016 thematics were optogenetics, COLLABORATIONS, OPEN INTERNSHIP FOR MEDICAL STUDENTS, THE STARE PROGRAM, translational and multi-modal MRI and neurodegenerative illnesses in collaboration with OURSELVES UP TO CROSS- BASED ON AN INITIATIVE DEVELOPED BY PROFESSOR JEAN- Yale. DISCIPLINARY APPROACHES YVES DELATTRE TO HELP 3RD YEAR MEDICAL STUDENTS ON RESEARCH PROJECTS DISCOVER RESEARCH AND FOSTER NEW CALLINGS TO VISITING PROFESSORESSOR CALL FOR WITH A LONG-TERM AND DEVELOP TRANSLATIONAL RESEARCH. PROJECTS INTERNATIONAL STRATEGY.” This call for projects aims at welcoming internationally-renowned senior researchers to "ALEXANDRA AUFFRET, ICM to pass along their knowledge. In 2016, we DIRECTOR OF THE SCIENTIFIC AND were pleased to welcome Professor David Hafler, MEDICAL AFFAIRS DEPARTMENT President of the Department of Neurology at New Haven .

54 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 55 MISSION NATIONAL AND INTERNATIONAL COLLABORATION

ICM is part of an international network that includes major neuroscience centers AT THE CROSSROADS OF INTERNATIONAL involved in shared research projects. Research carried out at ICM is assessed by an International Scientific Committee composed of experts from around the world. ICM is therefore both an attractive medical and scientific research hub for AND NATIONAL RESEARCH high-level researchers as well as a generator of novel scientific information on an international level. Our research ambitions require close cooperation with the most ICM IS PART OF AN INTERNATIONAL NETWORK THAT INCLUDES MAJOR NEUROSCIENCE CENTERS INVOLVED IN prestigious French and international research institutions. SHARED RESEARCH PROJECTS. THE INSTITUTE IS EMERGING AS AN ATTRACTIVE MEDICAL SCIENCE RESEARCH HUB FOR HIGH-LEVEL RESEARCHERS FROM AROUND THE WORLD.

With nearly 300 partnerships developed worldwide, ICM’s international reach is on the rise. These collaborations are an opportunity to share our breakthroughs and carry out shared research programs. Exchange programs are also in ICM is a cornerstones of the GREATER PARIS RESEARCH NEUROHUB (Neuropôle de Recherche place to develop training and skill-pooling. ICM aims to develop partnerships with institutions specialized in comple- mentary fields to meet transversal needs. Francilien - NERF) and the PARIS SCHOOL OF NEUROSCIENCE (École des Neurosciences de Paris - ENP), and partners with other high-level research centers throughout Paris: PIERRE ET MARIE CURIE UNIVERSITY, ÉCOLE NORMALE SUPÉRIEURE , VISION INSTITUTE, MIRCEN, NEUROSPIN, PASTEUR INTERNATIONAL COLLABORATIONS INSTITUTE… RESEARCH AT ICM IS DEVELOPED IN COOPERATION WITH MAJOR FRENCH NEUROSCIENCE CENTERS, AMONG WHICH:

UNIVERSITY COLLEGE OF LONDON DZNE LILLE MONTREAL NEUROLOGICAL INSTITUTE ICM MAX-PLANCK INSTITUTE MIT ISTUTO CARLO BESTA NEUROPATHOLOGY COLUMBIA UNIVERSITY NEUROSCIENCE DPT, YALE ECOLE POLYTECHNIQUE FEDERALE RIKEN BRAIN INSTITUTE SANDLER’S INSTITUTE, UCSF INSTITUT WEIZMANN

CAEN NEUROIMAGING STRASBOURG NEUROBIOLOGY, PARIS NEUROGENETICS

UNIVERSITY OF SAO PAULO LIMOGES

ALS AND FRONTO-TEMPORAL LYO N LOBE DEGENERATION FLOREY INSTITUTE NEUROPHYSIOLOGY, NEUROIMAGING

CLERMONT-FERRAND MOVEMENT AND SPINAL CORD THE INSTITUTE OF NEURO- YALE NEW HAVEN UNI- UNIVERSITY OF CALIFORNIA THE MNI (MONTRÉAL THE FLOREY INSTITUTE BORDEAUX DAMAGE REPAIR GRENOBLE LOGY VERSITY – SAN FRANCISCO NEUROLOGICAL INSTITUTE) (AUSTRALIA), NEUROPHYSIOLOGIY (University College for a clinician with for a student ENGINEERING of London, Royaume-Uni) exchange program. the implementation of a in Canada, with which ICM exchange program with SCIENCE, and the DZNE (Network of Inserm-certified Associated has organized joint events in short-term internships. Shared NEUROBIOLOGY research centers focused on International Laboratory the past and welcomed many seminars with our researchers TOULOUSE GÉNÉTIQUE, Neurodegenerative illness, with the team led by researchers on a variety of aim at fostering relationships NEUROIMAGERIE Germany) with research Bertrand Fontaine and topics. in research and education. Stephen Hauser. partnerships. ICM hopes to MONTPELLIER co-develop training and edu- NEUROPHYSIOLOGY, cation with these institutions. NEUROIMAGING MARSEILLE NEUROPHYSIOLOGY, NEUROIMAGING

56 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 57 MISSION CLINICAL RESEARCH 3 PILLARS : ETHICS, SAFETY, QUALITY The CIC takes ethics and safety very seriously when it comes to studies. Participants in trials are made aware of THE CLINICAL INVESTIGATION CENTER, CIC the benefits and possible risks. Each study receives a favorable opinion from an ethics committee as well as the TOWARDS TAILORED AND PERSONALIZED PATIENT TREATMENT drug administration (ANSM) before launching. Additionally, the drugs involved in clinical trials all go through a safety assessment process before the trial starts. THE CLINICAL INVESTIGATION CENTER OR CIC (INSERM, AP-HP), HOUSED IN TH ICM, IS AN EXCEPTIONAL PATHWAY BETWEEN RESEARCH AND CARE, OFFERING INNOVATIVE TREATMENT FOR PATIENTS AFFECTED BY 3 QUESTIONS CIC QUICK FACTS AU DIRECTEUR NEUROLOGICAL ILLNESSES. DU CIC 172 CLINICAL TRIALS IN PROGRESS 3 QUESTIONS FOR PROFESSOR JEAN-CHRISTOPHE CORVOL, CIC DIRECTOR DAILY CONTACT WITH 650 RESEARCHERS AND CLINICIANS

PARTICIPATING PATIENTS OF THE CLINICAL TRIALS HOW DOES THE CIC WORK? WHAT ARE ITS of the disease. Trials at the CIC also with Bioserenity to study a new 7 000 MISSIONS? WHAT IS THE RELATIONSHIP WITH demonstrated the existence of markers continuous monitoring device for THE NERVOUS SYSTEM DISEASES HUB AT PITIÉ- for remyelination potential and neuronal epilepsy, a study on the use of SALPÊTRIÈRE HOSPITAL? loss in patients, allowing prediction of revolutionary technology to block The CIC is located in ICM building, at disease progression and selection of a gene affected in certain types of the core of research. It maintains a the best possible treatment for each ALS, and a European project on strong relationship with the doctors patient. neuroprotective stem cell transplants in STEPS IN CLINICAL RESEARCH working in the Nervous System the early phases following a stroke. Diseases hub at Pitié-Salpêtrière In Parkinson’s disease, the CIC is taking hospital. This means we can easily part in a European trial on deferiprone, WHAT IS THE OUTLOOK FOR THE CIC IN THE Proof of Precision Routine Fundamental science Preclinical concept Phase II-III cohort studies care take laboratory discoveries right to an iron chelator with a supposed effect UPCOMING YEARS? the patient’s bedside and vice versa. in decreasing iron deposits in neurons Our project is to implement an even The Center aims at improving our and with a neuroprotective effect. The more unified vision of clinical research understanding of the humain brain NS-PARK/FCRIN network, that brings in Neuroscience within Pitié-Salpêtrière and pathologies, as well as grating together the 24 centers specialized in Hospital. patients rapid access to breakthroughs Parkinson’s disease in France, is also Two projects are going to help us NERVOUS in research to improve patient diagnosis involved in the trial (H2020 European accelerate the implementation of ICM CLINICAL and care. financial support, Lille University clinical trials: NeuroCatalyst and SYSTEM In 2016, the CIC officially merged with Medical Center as promoter). We are NeuroTrial. RESEARCH DISEASES HUB the Center for Therapeutic Assessment also coordinating a trial on dyskinesia Neurocatalyst will help projects mature (Centre d’Evaluation Thérapeutiques treatment, also called involuntary from fundamental research carried out - CET), a similar institution located movements, thanks to the same clinical by ICM researchers to breakthroughs in the Department of Neurology at research network and in partnership made available to patients. ICM Building Paul Castaigne Building Pitié-Salpêtrière Hospital. The goal with CleveXel. Neurotrial aims at encouraging research is to create a full clinical research done in partnership with industry platform, from ICM research on early Another great success for 2016 is the players to accelerate drug development Innovation Transfer Application drug development to assessment and study carried out by Emmanuelle Roze, and identify new assessment <---> <---> improvement of care, access to major proving the efficacy of zonisamide in instruments for drug efficacy as early international trials and innovative treating myoclonic dystonia, a rare as possible. medical devices with the Living Lab. illness. 172 drug trials are in progress Finally, a study is underway in throughout the Nervous System collaboration with Professor Richard Abnormal movement Diseases hub, half of which are at the Lévy’s team to give a detailed Neuro-oncology CIC-CET, in various fields of neurology assessment of apathy, lowered activity Cognition and psychiatry. levels linked to decreased motivation MS in many neurodegenerative illnesses. WHAT ARE SOME HIGHLIGHTS OF 2016 This is done using the PRISME “real- Vascular CLINICAL TRIALS THE CIC TOOK PART IN, AND life” platform, used for observation and Epilepsy THE MAJOR TRIALS TO COME? analysis of patient behavior in semi- Neurological Resus- The CIC took part in three major natural conditions. citation multiple sclerosis clinical trials that ALS demonstrated the efficacy of two Starting in 2017, we will be launching Psychiatry new treatments for progressive forms various trials including a collaboration Metabolism Genetics Peripheral Nervous

58 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 59 MISSION CLINICAL RESEARCH

2016 HIGHLIGHTS THE INSIGHT PROJECT THE NERVOUS SYSTEM COORDINATED BY BRUNO DUBOIS, PROVIDING AN EXCEPTIONAL AMOUNT OF RESEARCH ON VERY EARLY DISEASES HUB, NSD PROVEN EFFICACY DIAGNOSIS OF ALZHEIMER’S DISEASE. TO GIVE PATIENTS ACCESS TO THE LATEST OF A DRUG BREAKTHROUGHS IN TREATMENT TO TREAT MYOCLONIC DYSTONIA, A RARE ILLNESS, WITH DESCRIPTION OF NEW SYMPTOMS WITH OVER 80,000 CONSULTS PER YEAR, THE NERVOUS SYSTEM RESEARCH CARRIED OUT BY IN PATIENTS WITH BEHAVIORAL DISORDERS DISEASES HUB,(OR NSD HUB) IS ICM’S HOSPITAL COUNTERPART. EMMANUELLE ROZE. AND AFFECTED BY APATHY, THANKS TO WORK DONE IT POOLS TOGETHER THE DEPARTMENTS OF NEUROLOGY, CONVERSATION WITH BY THE BEHAVIORAL UNIT (UNITÉ PROFESSOR JEAN-YVES PSYCHIATRY, FOLLOW-UP CARE AND REHABILITATION, AS WELL AS DE NEUROPSYCHIATRIE COMPORTEMENTALE - UNPC) DELATTRE, ICM MEDICAL THE NEUROPHYSIOLOGY AND NEUROPATHOLOGY DEPARTMENTS DIRECTOR AND NSD HUB AT PITIÉ-SALPÊTRIÈRE HOSPITAL. THE NDS HUB’S ACTIVITY WHERE NEUROLOGISTS, PSYCHIATRISTS CHIEF AT THE PITIÉ- IS BASED ON THREE PILLARS: DIAGNOSING, TREATING, AND AND RESEARCHERS COLLABORATE. SALPÊTRIÈRE HOSPITAL REHABILITATING.

THE NSD HUB IS A PARTNER OF following questions: did we use the most psychologists…): we want every single precisely everything that is going on in between medical care and clinical research, CHOICE FOR ICM, HOW DOES THEIR modern techniques available, here at ICM, member of our staff to be part of their own clinical research in our 10 departments - both dedicated to our patients. Along with COLLABORATION WORK? for the patient? Is there a research project research, be it in healthcare or quality of how many innovative trials we have offered this vast work in progress, Professor Bruno The collaboration between ICM and the planned to improve current knowledge on life, and ICM is helping them with training our patients, how many patients we are Dubois is driving a project to consider NSD Hub is growing, and doing well. The the patient’s illness or treatment that we on methodology. involving per month, etc. - with the hope building a facility right next door dedicated “Clinical Research” entities of ICM and NSD can ask the patient to participate in? The Living Lab is a great example that as many patients as possible can to clinical research on neurodegenerative Hub are on their way to becoming a single of collaborative research. Clinicians, benefit from new treatments. Designing diseases, with close ties to ICM. This would entity, a neuroscience clinical research WHAT ARE SOME BREAKTHROUGHS FOR researchers, paramedical staff, patients an innovation-centered department means be an opportunity to build a fast-track powerhouse at Pitié-Salpêtrière Hospital. 2016? and developers work hand in hand to getting used to that culture, which is why between the NSD hub and ICM to develop We are also putting the finishing touch As I said earlier, one of the major advances design, develop and create innovative we have started gathering these indicators. innovative treatment. on a clinical research facility managed by for 2016 was the launch of a clinical instruments for improved patient care. Professor Jean-Christophe Corvol. The research unification process between Projects for a new “medical beds”, 3D We also hope to implement ICM “Clinical driving forces behind it come from the the hub and ICM with Professor Jean- cranioplasty as well as a cane emitting light research team” certification for NSD hub IN YOUR EYES, WHAT DOES TOMORROW’S hub (AP-HP), INSERM, and ICM (doctors, Christophe Corvol. The resulting asset to help Parkinson’s patients start up are all departments with a deep involvement MEDICAL WORLD LOOK LIKE? paramedical staff, statisticians, etc.). It goes much further than the CIC-CET. 172 examples of real-life applications that help in this field. Rigorous assessment by an It will be predictive, and fully tailored to should be fully operational by the end of clinical trials are currently in progress led our patients and improve their daily life. international jury would be a prerequisite, patients who are informed and looking to 2017. by NSD Hub and ICM teams - quite a lot. quite like what is already in place for make their own decisions. Medicine has Another progress we’ve made is going WHAT ARE SOME MAJOR UPCOMING fundamental (laboratory) research teams always progressed by identifying different WHAT STEPS DOES A PATIENT WITH A forward in planning the “Neurotrials” and PROJECTS? at ICM, to improve our clinical research entities that can be impacted by different NERVOUS SYSTEM ILLNESS GO THROUGH “Neurocatalyst” projects, which will help For the first time, the NSD hub il going to expertise. treatments, in what looks at first like a AT THE NSD HUB? us have the full clinical research process dedicate part of its budget to supporting common framework. I don’t see why this The first step is establishing the correct on-site, from proof of concept of a drug to a clinical research project initiated by a Finally, some great news is that we are should change at all. I also strongly believe diagnosis using our medical experts large-scale assessment in Phase III studies young doctor. It is absolutely essential to opening a new building, “Paul Castaigne”, that we will listen to what patients have to and the technical platform we have on a national or international level. give young colleagues the drive to invest in December 2019. The building will be say, including when it comes to deciding on-site. Next, we draw up a healthcare We’ve also implemented specific training in clinical research as early as possible in dedicated to Neurology for the entire what their future holds in the case of plan suited to the patient with the help to develop a research culture among their career. Pitié-Salpêtrière Hospital. This huge project terminal and disabling illness. of a multidisciplinary team. At each and the hub’s paramedical staff (nurses, Another project we have right now is is a great opportunity for us to rethink every step, we have to ask ourselves the assistant nurses, physical therapists, developing indicators to help us monitor our organization and create a tighter link

60 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 61 MISSION KNOWLEDGE SHARING & INNOVATION RESEARCH & TECHNOLOGY DEVELOPMENT OFFICE: WHAT TO KNOW

1 TELEMEDICAL platform € created by shared laboratory HOW DOES THE RESEARCH & TECHNOLOGY Brain eNovation One of the highest growths Over among the Carnot Institute 100 million DEVELOPMENT OFFICE (DAR) TRANSFORM network Diagnostic solutions for epilepsy euros raised by our startups – developed by DISCOVERIES MADE BY OUR RESEARCHERS 120 entrepreneurs on-site BIOSERENITY installed in over 30 HOSPITALS INTO THERAPIES? 27 companies incubated at iPEPS-ICM since 2012, CERTIFICATION 3 are international of 2 Biological Resource Center platforms 5 QUESTIONS TO ALEXIS GÉNIN, 200 industry partnerships OPENING OF THE DIRECTOR OF THE RESEARCH & TECHNOLOGY DEVELOPMENT OFFICE LIVING-LAB MOBILE APPS where patients, researchers, to monitor multiple sclerosis clinicians and developers work developed by Ad Scientiam “OUR GOAL IS TO DETECT his mission starts with early detection of research results that could OVER 50 PATENTS together to design new PROMISING SCIENTIFIC lead to applications, their protection with patents, financial support therapeutic solutions BREAKTHROUGHS Tfor proof of concept to get from an idea to a proven idea, and finally, In a world first, Carthera , TO DEVELOP THEM INTO medical device designer finalizing inventions and new drug or medical technology development. All 2 laboratories, recipients of the and developer, was granted THERAPEUTIC SOLUTIONS of this is possible thanks to our “Carnot Institute” certification that supports « INNOVATION 2030 » :

AS QUICKLY AS POSSIBLE” development of research partnerships and transfer of technology between Bio-electrics lab 5,7 million euros in financial support public research and businesses, as well as the Living Lab and iPEPS-ICM, and Brain eNovation 1 DRUG by the French administration. ALEXIS GÉNIN, DIRECTOR a business incubator and France’s top innovation accelerator dedicated to developed by MEDDAY OF THE RESEARCH & TECHNOLOGY brain illnesses. 16 innovative startups working in digital technology, medical to fight multiple sclerosis DEVELOPMENT OFFICE. technology and drug development are currently incubated.

HOW DOES THE DAR DEVELOP DID THIS PROCESS CHANGE AT ALL IN fields to foster successful developments, national level. In fact, partnerships with our are working with excellent chemists others used to halt disease progression. DISCOVERIES INTO THERAPIES? 2016? with our eyes turned towards the rest of technological platforms grew over 25% in specialized in natural molecules to help Our mid- and long-term mission is to The first phase is based on interaction, We have been takin g a much more the world to position the Carnot brand on 2016. identify future drugs using traditional bring therapeutic solutions for patients to detailed discussions with researchers and proactive approach in order to lead an international level. Next is the Living Lab, certified to join medicine. market. Starting 2017, we hope to prove doctors to find comparable data that may product development ourselves by In 2016, Carnot financial support helped the European Living Lab network called We also need to employ other clinical efficacy for one project and verify exist elsewhere in order to characterize founding startups. ICM isn’t only bringing bring a dozen projects to fruition, and ENOLL. The first functioning prototypes approaches: businesses specialized in the benefits of 2 to 3 medical technologies how new and innovative the finding is. This expertise and skill to the table to help supported the filing of 7 patents, the to come out of the Lab have already been medical technology development, for for patient use. Thanks to the Future phase is always undertaken secretly, and other startups develop drug, it is now a Institute’s ongoing commitment to developed on an industry level, a sole 18 example, are very dynamic and can give Investments Program (IHU), we will have this is when we decide to grant an initial product developer itself. I would say that quality, and international development. In months after the Lab was started. us a different outlook on how to think support from a new project, NeuroCatalyst, package for financial support. As a Carnot was the major change of the year. February, ICM was part of a major Carnot Finally, receiving “French Tech Ticket about illness. Wearable medical devices, that will allow greater investment in Institute, we have access to resources to event: the French American Innovation incubator” certification by the Ministry of mobile applications, smart objects, and clinical research. Additionally, in 2017 help us verify an idea’s value or results, and ICM RECENTLY RECEIVED “CARNOT 3” Days, in Boston, where the Carnot Institute Economy illustrated our ability to support therapeutic gaming could become part our expansion to the Station F startup their potential development into products CERTIFICATION, WHAT CHANGES ARE model in healthcare was presented to the international companies. It’s important to of global patient care. Active prevention campus will allow new “digital” healthcare to help patients. INVOLVED? American business ecosystem. note that in 2016, startups incubated with is also an interesting field to look at, startups to come to life and will help foster The second phase is protection of The main Carnot missions remain the same: us raised over 60 million euros in funding. especially nutrition and physical activity, if innovation interactions. intellectual property, when a patent is filed. professoressionalism in our relationship WHAT ARE SOME OF THE DAR’S MAJOR we can prove their efficacy and integrate After this phase, the project can “mature”, with industry players, responsiveness, ACHIEVEMENTS FOR 2016? them into structured patient programs. with the help of industry partners and integration within a multi-thematic First of all, I’d like to mention our work HOW DOES THE DAR MEET CURRENT We really are trying to understand patient investors. At times, we invest in projects network of institutes from energy to in coordinating FindMed, a network of CHALLENGES IN THE DEVELOPMENT OF care as a whole rather than take a solely ourselves to help push them as far as nanotechnology and health. Along with our 10 major Carnot institutes. This shows NEW THERAPEUTIC OPTIONS? medication-based approach, and are we can until a partner can take over and colleagues in the Carnot galaxy, we create that ICM can position itself as a point We are hard at work developing new attempting to develop integrated solutions sponsor product development. pathways between the various industrial of reference in business services on a ways to use existing medication, and where drugs are one element among many

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10 10 PROJECTS THE LIVING LAB CREATIVITY WORKSHOPS in close collaboration with hospital staff and patients, DESIGNING FUTURE MEDICAL INNOVATIONS including 4 finalized in 2017

TOGETHER, TODAY 100 ENOLL CERTIFICATION individuals from diverse backgrounds, (European Network of Living Labs) doctors, patients, paramedical staff, 5 QUESTIONS FOR ALEXIS STEINER, designers, sociologists, developers, engineers The world’s only neurology LIVING LAB MANAGER living lab

300 IDEAS WHAT IS THE LIVING LAB, EXACTLY? feeding disorders (children experiencing INTERNATIONAL REPUTATION It is a collaborative platform where trouble dealing with food) with UPCOMING PROJECTS patients and hospital staff are right at the therapeutic cards, improving cranioplasty FOR 2017 heart of innovation design. in the operating room, robotics to support It is a free space, away from hospital life, cognitive rehabilitation of stroke or head where different approaches and opinions injury patients, allowing prediction of To increase patient implication in from researchers, engineers, doctors, behavioral crises in patients with autism: cognitive rehabilitation, we created hospital staff, patients, students, startups, these are some of the projects developed FINDMED and more can interact to come up with at the uCIL Living Lab. a robot in collaboration with AI the most innovative ideas possible. CREATING PATHWAYS BETWEEN ACADEMIA MERGENCE, a startup. THE ROBOT 2 SUCCESS STORIES FOR 2016 AND THE DRUG INDUSTRY ITS MISSION With the support of a patient from HELPS THE OCCUPATIONAL THERAPIST It aims to create innovative medical the France Parkinson Association, we devices to improve patient care in developed a cane that emits visible light DURING THERAPY SESSIONS at the neurology and psychiatry. Our goal is FINDMED is a consortium coordinated by ICM, with Damien Salauze to get rid of the freezing effect, when hospital, and the patient can then to launch our innovations and bring patients are suddenly unable to move, as Operations Director. It is composed of 10 Carnot Institutes and aims them to market quickly thanks to help and to help Parkinson’s patients take bring it home where it provides from the Research and Technology a first step. Thanks to support from an at implementing partnerships with small to mid-size French drug Development Office, either with operating industry partner and France Parkinson, assistance for rehabilitation exercises. manufacturers. licenses negotiated with industry players, we hope to make this device available to The project is financed by a Carnot collaborations with businesses, or even by every patient soon. creating dedicated startups. A topic that we spent some time on is call for projects, and AI MERGENCE will improving everyday life for patients with FINDMED is a French governmental initiative to support FINDMED KEY FIGURES HOW DOES IT WORK? long-term hospital stays and how to give enter the incubator in 2017. competitiveness of drug manufacturers by granting them access to To put forward a solution, we need to them some privacy. We collaborated 10 CARNOT INSTITUTES, INCLUDING 6 LEADERS identify a need, first of all, and describe with a design school, hospital staff and A test provided free of charge academic research and the associated technological means. it with the help of patients and hospital patients and came up with a visually- IN THE HUMAN AND ANIMAL HEALTH FIELDS staff. Next, we try to find a creative pleasing mobile wall with an integrated to detect CEREBELLAR DISORDERS CONTRACTS WITH INDUSTRY PLAYERS solution to this need by imagining what night stand and technical supply unit (CCFS). Blueprints to make the box 175 the ideal solution would look like. Finally, (light, oxygen…) that isolates patients. A (EXCEPT LARGE GROUPS), INCLUDING we bring the idea to life as quickly as prototype was produced with external will be available online for free, The technological platforms of the various Carnot Institutes in the we can by testing a prototype from a suppliers and approved by all the allowing anyone to make their own 32 VERY SMALL BUSINESSES (1.2 M€ REVENUE) technological, clinical, and financial point participants in the project. A hospital consortium blend cutting-edge equipment with expertise, allowing of view. furniture supplier is on board to produce and take the test at home. industrial partners to bring their projects to life and innovate with 66 SMALL AND MID-SIZED BUSINESSES (5.2 M€ and sell the product. SOME NEW PROJECTS IN 2016 REVENUE) OPENING OF A FABLAB ET ICM, equipment tailored to their needs. Encouraging functional rehabilitation after patients are discharged from the hospital, a prototyping workshop right at the ICM’s nomination as project coordinator anchors the Institute as a 30 INTERMEDIATE BUSINESSES (2.8 M€ diagnosing a risk of reduced autonomy to leader in business services. REVENUE) improve elderly patient support, treating heart of the building in collaboration with the CENIR platform and BEBG 56 CUTTING-EDGE TECHNOLOGICAL PLATFORMS team.

64 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 65 MISSION IPEPS-ICM INCUBATOR

AN INCUBATOR TO SUPPORT STARTUPS

ICM’S IPEPS INCUBATOR FOLLOW YOUNG INNOVATIVE COMPANIES THROUGHOUT THEIR DEVELOPMENT TO TRANSFORM IDEAS INTO THERAPIES. THEY BENEFIT FROM AN IDEAL ENVIRONMENT, AT THE HEART OF A CUTTING-EDGE RESEARCH INSTITUTE, ITSELF RIGHT IN THE MIDDLE OF A HOSPITAL”

JULIEN ELRIC, START-UP MANAGER AT THE RESEARCH & TECHNOLOGY DEVELOPMENT OFFICE. FROM BIOTECHNOLOGY TO E-HEALTH

The 16 startups incubated at ICM FINDING THE PERFECT PROJECT cover all facets of neuroscience, from medical technology, to The incubator’s goal is to develop discoveries, ideas and innovations from ICM laboratories or from biotechnology and e-health. the outside. A project’s potential is evaluated in collaboration with ICM researchers and clinicians that take part in the decision to create an ICM-incubated company. The incubator also has a forward-looking approach, taking part in international conventions, scientific conferences and competitiveness centers to identify projects that could be a good fit with ICM.

RAISING FUNDS

The incubator helps companies raise funds as drug and medical device develop is very costly. ICM startups have succeeded in raising over 100 million euros since 2012 both in private and public funds. To support A TURNING POINT companies in their development, the incubator relies on various In 2016, a truly proactive partners including the Public Bank for Investment (Banque publique approach was imple- d’investissement), the primary financial partner for startups, and a vast mented with partnership network of investors. ENCOURAGING development, a search for INTERACTION foreign companies to build an international vision, Cross-fertilization is one of and even stronger support the incubator’s core ideas: through share ownership encouraging interaction for some companies. ACCELERATING INNOVATION and collaboration between companies through staff Supporting startups is an everyday affair, to help them transform and equipment pooling, their idea into a professoritable business that will succeed in through conversations bringing an innovation to market. Some activities are: reviewing between researchers and business plans, helping create a pitch, developing a company clinicians… This collaborative presentation for potential investors, introducing them to investors, environment is what leads streamlining costs, and more. our projects to success.

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ACTIVITY: Innovative digital ACTIVITY: The Neuronaute, ACTIVITY: Applications for instruments in healthcare, smart clothing for at-home improved patient care at especially therapy video epilepsy monitoring home or in a hospital games. setting. 2016 HIGHLIGHT: 4 m€ 2016 HIGHLIGHT: Publication revenue in 2016. Over 32 2016 HIGHLIGHT: 1 million of results in Journal Of hospitals currently use their euros raised and renewed Alzheimer’s Disease digital solutions. partnership with Roche. verifying efficacy and Presentation of clinical trial LES START-UP DE l'ICM patient tolerance in a pilot results and proof of concept usability and acceptability for their future medical study of therapeutic video device to the ECTRIMS. game -TORP designed for Several research contracts patients with Alzheimer’s with the pharmaceutical disease and associated industry. illnesses. ACTIVITY: Innovative medical ACTIVITY: Non-invasive ACTIVITY: Neuroprotective Financing of a new Europe- devices designed to treat methods based on spinal molecules used against wide study in partnership brain illnesses. cord stimulation neurodegenerative illnesses with Rabdoud University ACTIVITÉ : Screening (trans-spinal direct such as Parkinson’s disease. in the Netherlands for instruments for 2016 HIGHLIGHT: financial current) for treatment therapeutic video game ACTIVITY: medical devices for 2016 HIGHLIGHT: neuroprotective support of 5.7 million of patients with motor Founded TOAP Run designed for neurology/neurosurgery, molecules in various euros in the “Research and disorders. in February 2016 and patients with Parkinson’s specifically for patients with neurodegenerative illnesses Development Projects for incubated at ICM in disease, within the H2020 intracranial hypertension Competitiveness” (“Projets September. Obtained an program. de R&D Structurants exclusive license to use ACTIVITÉ : Diagnostic 2016 HIGHLIGHT: Official Launch of the ReMinAry Pour la Compétitivité” an ICM molecule that de la maladie d’Alzheimer. launch of the company. project to implement - PSPC) project of the may have a major effect In vivo proof of concept, rehabilitation through Motor Future Investments in treating Parkinson’s. Scientipôle interest-free Imagery, based on the Program (Programme 2016 Scientipole Initiative ‘honor’ loan and PIA (BPI) cognitive process whereby d’Investissements Winner and recipient of the a patient mental simulated financing d’Avenir - PIA), led by the Emergence French Tech an action without actually General Commissioner for Grant. performing it. The online ACTIVITÉ : Measuring Investment (Commissariat platform curapy.com, that instruments to detect Général à l’Investissement gathers therapeutic video blood-brain barrier crossing - CGI) and operated by games with proven efficacy (that prevents molecules Bpifrance for its DOME in clinical trials, is finishing from entering the brain) by ACTIVITÉ : Outils d'analyse project. up its “test phase” year molecules biostatistique. with over 3,000 healthcare professoressionals signed up.

68 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 69 MISSION SUPPORT OUR MISSION SOPHISTICATED TECHNOLOGICAL PLATFORMS FOR HIGH-LEVEL RESEARCH

HIGH-PERFORMANCE TECHNOLOGCAL PLATFORMS ARE NECESSARY TO ACHIEVE MEANINGFUL SCIENTIFIC BREAKTHROUGHS. ICM IS BOTH REVOLUTIONARY IN ITS DESIGN AND INNOVATIVE IN ITS ORGANIZATION, AS WELL AS UNIQUE IN ITS CUTTING-EDGE TECHNOLOGICAL EQUIPMENT. ICM RESEARCHERS WORK AT VARIOUS SCALES: FROM MOLECULES (DNA, PROTEINS,…) TO CELLS, TO INDIVIDUALS AS A WHOLE. AT EACH SCALE, INNOVATIVE TECHNOLOGY IS MADE AVAILABLE TO RESEARCHERS AND CLINICIANS. ICM PLATFORM NETWORK ENABLES TRANSLATIONAL RESEARCH, WITH AN IMPORTANT RELATIONSHIP FORGED BETWEEN RESEARCHERS AND CLINICIANS.

5 QUESTIONS FOR ETIENNE HIRSCH, DIRECTOR OF PLATFORMS

HOW DO WE ENSURE COMPETITIVE WHAT’S NEW FOR 2016? involved in certain familial forms or RESEARCH RESULTS? In 2016, we launched a call for tenders to Parkinson’s disease caused by a Parkin Progress in biology and medicine needs encourage platform competitiveness and protein genetic mutation. They showed strong technology and advice from the incite them to develop methodological and that the protein seems to act as a best experts in their field. In fact, most technological research. regulator of calcium channels between the major discoveries are thanks to technical 3 projects were financed with this call for endoplasmic reticulum and mitochondria, and methodological progress. tenders: the cell’s energy generator thought to - The DISCO method to make brain tissue play a pivotal role in the disease’s various WHAT IS THE MISSION OF THE PLATFORMS? transparent and thus “peruse” through the forms. Shedding light on this process that The human brain is our body’s most brain and see neurons in 3D is responsible for the death of neurons complex organ. Understanding how it - Automation of gene analysis to involved in Parkinson’s disease gives us functions and the associated pathologies implement experimental modelling new insight into possible therapeutic means acquiring data at every level - New functional testing to study activity opportunities. (molecular, cellular, neural network…) of human neuron cultures, derived from and at each moment. For ICM founders, induced pluripotent stem cells WHAT’S NEXT? it was important to give research teams This R&D activity is essential to diversify We hope to maintain and reinforce the instrumental and organizational the technological offer of our platforms platform competitiveness with a second capabilities to meet their goals. From the and meet the needs of research teams. It call for tenders, “research and development start, ICM was structured around high-level is also an opportunity to provide a return in 2017”. We will also be assessing activities technological and human resource pooling on ICM’s investment in our platforms and carried out by platforms that received to necessary to research development. ensure its long-term viability. investments from our public partners. Beyond making innovative instruments and equipment available - high-performance OUR 2016 SUCCESS STORY? microscopes, MRI, PET-MRI, high-speed Thanks to CENIR cutting-edge brain sequencer… - the mission of our platforms imaging, researchers in the team led by is sharing technical skills and offering Stéphane Lehéricy and Marie Vidailhet services and expertise. The platforms are identified a marker in a pre-symptomatic open to the entire scientific community: variant of Parkinson’s disease, in which ICM research teams, outside academic patients present isolated behavioral teams, incubated companies and outside disorders during REM sleep. This marker companies. could be used as a diagnostic test for These platforms are an opportunity for future patients. Thanks to the various researchers to widen the scope of their cellular exploration techniques at research and exploration by giving them CELIS, Olga Corti in Alexis Brice’s team access to unique resources. highlighted the cellular mechanisms

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Implementation of easy-to-handle cell cultures to reproduce and study nervous system pathology mechanisms. ICM PLATFORMS CELIS – Cell culture platform ICM PLATFORMS FOLLOW A SILO ORGANIZATION BASED ON THEIR SCALE: MOLECULAR EXPLORATION, Cell models and cutting-edge technology used to study brain and spinal cord pathology, as well as screening of potential medication. CELLULAR EXPLORATION, IMAGING, PRECLINICAL FUNCTIONAL EXPLORATION, FUNCTION EXPLORATION, CELIS-E-PHYS – Electrophysiology platform BIO-INFORMATICS AND BANKS. Record electrical activity within cells in various experimental conditions (isolated cells, tissue samples). CELIS-iPS – Platform for the production of human induced pluripotent stem cells Development of human induced pluripotent stem cells (iPS). Histomics – Histology platform MOLECULAR EXPLORATION Study of tissue samples.

Genome analysis and development of viral vectors iGenSeq - genotyping-sequencing platform Genome analysis, detection of possible genetic mutations and identification of possible relationships between mutation and pathological signs. iVector - vectorology platform Production of viral vectors used for gene therapy used by ICM researchers in the hopes of “repairing” damaged DNA in patients. BIOLOGICAL RESOURCE CENTER

Samples collected during blood tests, biopsies, or other surgical actions are an extremely precious source of information in research. The ICM is home to 3 biobanks dedicated to managing these biological resources (biological samples and associated data): collecting, recording, processing, storing, and CELLULAR AND MOLECULAR IMAGING making them available to researchers. The DNA and Cell Bank 360° cellular observations, classic and photon microscopy Biological resource center for the French Network for Multiple Sclerosis Photon optogenetic electron microscopy, fluorescence microscopy, Genetic Studies (CRB-REFGENSEP) 3D microscopy, light sheet microscopy, etc. The Tumor Bank : OncoNeuroTek

PRECLINICAL FUNCTIONAL EXPLORATION

Study of living organisms in experimental models ICONICS BIOINFORMATICS PHENO-ICMice – Rodent Model Platform PHENO-ZFish- Zebrafish Model Platform Neuroscience research has seen a spectacular increase in the sheer amount of data collected in labs. The role of the iCONICS Bioinformatics silo is to collect PRISME – HUMAN BEHAVIOR data from various sources and ensure it is properly stored, organized, and managed with appropriate EXPLORATION PLATFORM instruments to analyze it and interpret it using FUNCTIONAL EXPLORATION specialized methods and detailed statistics. PRISME - Virtual Reality : makes virtual reality Database and Datawarehouse instruments adapted to cognitive and behavioral Groups data within databases, all developed with the Study of living organisms using non-invasive and respectful methods, particularly adapted neuroscience available for use by researchers. same structure to format and manage, on a daily basis, to both healthy volunteers and affected patients. The platform also develops new equipment and information from affected or healthy patients. CENIR – Human MRI – Research neuroimaging platform High-quality imaging instruments for brain and spine research. therapeutic protocols for neuropsychiatric illnesses. Bioinformatics/Biostatistics CENIR- MEG/EEG – Magnetoencephalography and Electroencephalography platform - Non-invasive methods for PRISME – Real Life : dedicated to the study of Genetic and –omic (transcriptomic, genomic, visualization of cerebral activity with millisecond precision. cognitive functions, motor performance, and social epigenomic) data processing. Design and CENIR- STIM – Stereotaxic platform interactions in ecological environments. The platform implementation of advanced methods to multimodal Program development and analysis using stereotaxic imaging data (uses include deep brain stimulation, drug-resistant team assists research teams in the development of data integration. adapted protocols. One of the platform’s greatest epilepsy and radiosurgery).. strengths lies in its ability to test a large number of CENIR-PANAM – Physiology and movement analysis platform subjects to increase representativeness. Clinical and therapeutic research using non-invasive brain stimulation, motor control studies and multidisciplinary

association of various techniques. CENIR –Small Animal MRI MRI Platform for small animals Experimental pathological model platform for assessment of new biomarkers, the study of pathology mechanisms, and drug assessment.

72 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 73 DILIGENCE AND TRANSPARENCY AT THE HEART OF OUR ACTIONS

MAINTAINING A HIGH LEVEL OF EXCELLENCE IS KEY FOR ICM, WHICH IS WHY THE INSTITUTE IMPLEMENTED INTERNAL AND EXTERNAL AUDITING PROCEDURES TO ENSURE THOROUGH AND EFFICIENT MANAGEMENT: AS A MEMBER OF THE TRUSTED DONATIONS COMMITTEE AND INVOLVEMENT OF AN INDEPENDENT AUDITOR.

Financial situation in 2016 p.76

74 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 75 DILIGENCE AND TRANSPARENCY 2016 FINANCIAL STATEMENT OPEN BOOKS

THE 2016 BALANCE STATEMENT SHOWS ICM AND ADREC OPERATIONS POST-MERGER FOR THE FIRST TIME. CONSEQUENTLY, THE ICM’S 2016 CONSOLIDATED BALANCE STATEMENT INTEGRATES ASSETS AND LIABI- LITIES FOR BOTH ENTITIES AND TAKES INTO ACCOUNT THE IMPACT OF THE BUILDING’S CONSTRUCTION, HISTORICALLY SUPPORTED BY ADREC (WITHIN A PUBLIC DOMAIN PROVISION) IN TERMS OF FIXED ASSETS AND LOANS. CASH FLOW IS ALSO ON THE RISE THANKS TO ADREC LIQUID ASSETS. THE ICM’S SCOPE OF CONSOLIDATION IN ITS 2016 BALANCE STATEMENT REMAINS HEALTHY. ICM IN FRANCE

ICM CONTINUED ITS REGIONAL EXPANSION IN 2016. THREE REGIONAL BRANCHES (LIMOUSIN, BASSE-NORMANDIE AND AUVERGNE) FUNDRAISING IN-KIND DONATIONS AND WERE ORGANIZED AROUND THE FOLLOWING GOALS: SPONSORSHIPS 15.2 M€ WERE RAISED IN 2016, AN 9% INCREASE COMPARED TO 2015. Reinforce visibility, reputation, and attractiveness of ICM amongst donors, the general public, and economic and political figures; Major patronage agreements signed with foundations or MANY COMPANIES HAVE OFFERED THEIR SUPPORT BY CONTRIBUTING Contribute to the development of ICM’s financial resources to accelerate scientific discoveries companies in 2016: SKILLS FROM THEIR FIELD, OR BY DONATING PRODUCTS FREE OF with its own research teams and regional, national and international partnerships; Groupe Pasteur Mutualité to support ICM’s research CHARGE. IN THIS SECTION ARE ALSO FEATURED ARTISTS AND Encourage ties between ICM and regional neuroscience research partners and promote collaborations. mission COLLECTORS WHO HAVE DONATED WORKS OF ART TO BE SOLD, Edmond J. Safra Foundation The for research project BENEFITING ICM. funding Fonds Brou de Laurière, for research project funding

THE CIRCLE OF FRIENDS OF ICM BRINGS TOGETHER DONORS ICM has received in-kind support within the scope of communication and fundraising activities in the form BALANCE SHEET WHO HAVE SUPPORTED ICM FROM ITS INCEPTION, of: WITH DONATIONS OF 10,000€ OR MORE. Media placement from Air France, Reedexpo/FIAC, Euronews; 2016 RESOURCES The Circle was created as a means of giving special Complimentary services and products (Air France, thanks to important donors, individuals, companies, Publicis, Orrick Rambaud Martel, Quaterback, IDEC, 2016 resources reached 39.9 M€, including fiscal year products of 32.5 M€ and a carryover of allocated and or foundations, who very actively participated in the Moët & Chandon, Hôtel Barrière Le Fouquet’s Paris, unused resources from previous fiscal years of 7.4 M€. Fiscal year professorits are essentially made up of Fundraising Campaign launched by ICM in 2008. fundraising revenue (15.1 M€ or 46.5%), general public donations (11.9 M€ or 36.6%), companies and private 600 Crédit Agricole Centre Ouest). At the end of 2016, the Circle had nearly foundations (3.2 M€ or 10%). members. Luxury products, collectibles, art and other objects for the auction held during the Institute’s charity Exclusive activities are organized to thank them for Additionally, they include: auction (Enrico Navarra Editions, Akbar Padamsee, their support and to help donators meet and discuss Kamel Mennour Gallery, Gérard Garouste, Gilles Le • Revenue from technological platforms (3.3 M€), and research partnerships with industry partners (3.2 M€); with researchers, and are also a means of giving them Baud, Camille Henrot, François Henrot, Fabrice Hyber, • Public subsidies (5.5 M€); more in-depth information regarding research outlooks Francis Joyon, Cyril Kongo, Bertrand Lavier, Claude • Private subsidies (2.1 M€). and how donations are used. Lévêque, Montres FP Journe Paris SAS, Richard Mille, Maurice Lévy and David de Rothschild, Founding François Morellet, Bettina Rheims, David de Rothschild, Members of ICM, currently serve as Circle co-presidents. Domaines Barons de Rothschild, Guy Savoye, Vanessa In 2016, ICM organized a charity diner at the von Zitzewitz, Jean Todt, Romain Grosjean, Cité du Conciergerie in Paris on June 8, 2016, for the Circle of Cinéma, Hôtel Intercontinental Paris, FIA). 10% Friends of ICM.

GENERAL PUBLIC FUNDRAISING 37% OVER THE YEAR, ICM CONTINUED ITS DIRECT MARKETING PRIVATE FOUNDATION AND CORPORATE FUNDRAISING 23% STRATEGY, INITIATED IN 2010, TO INCREASE ITS DONOR BASE. ACTIVITY REVENUE Fundraising campaigns raised 6.4 M€ over the course of PUBLIC AND PRIVATE SUBSIDIES the fiscal year and donor base increased to 144,000 by OTHER REVENUE end of year. 20% Finally, ICM is especially grateful to families who 10% collected donations in memoriam for the Institute.

76 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 77 DILIGENCE AND TRANSPARENCY 2016 FINANCIAL STATEMENT

2016 APPLICATIONS SIMPLIFIED BALANCE SHEET

IN 2016, THE GRAND TOTAL OF APPLICATIONS REACHED 38.8 M€: 30.9 M€ USED OVER THE COURSE OF THE YEAR AND 7.9 M€ ALLOCATED FOR Assets (k€) 31 12 2015 31 12 2016 FUTURE USE. THE SHARE OF APPLICATIONS DEDICATED TO SOCIAL MISSIONS REACHED 24.9 M€, 81% OF TOTAL FISCAL YEAR APPLICATIONS. Net immobilized assets 9 963 54 276 ICM SOCIAL MISSIONS INCLUDE: Net available and realizable assets 35 108 50 399 Total 45 071 104 675

RESEARCH PROJECTS (55 %)

TECHNOLOGICAL PLATFORMS (27 %) Liabilities (k€) 31 12 2015 31 12 2016 SCIENTIFIC EVENTS AND INTERNATIONAL PARTNERSHIP DEVELOPMENT (5 %) Organization funds 19 101 44 498 INNOVATIVE COMPANY INCUBATION (13 %) Fiscal year result 766 1 191 7% Dedicated funds 7 464 7 919 Debts 17 740 51 067 12% Total 45 071 104 675

SOCIAL MISSIONS FUNDRAISING AND COMMUNICATION FEES COMMENTS OPERATING COSTS 81% TOTAL ICM INVESTMENTS SINCE THE INSTITUTE’S LAUNCH REPRESENT NEARLY 24.5 M€, DEDICATED PRIMARILY TO TECHNOLOGICAL PLATFORMS SUPPORTING RESEARCH. FISCAL YEAR INVESTMENTS AMOUNTED TO 2 M€.

PRINCIPAUX INVESTISSEMENTS : Key equipment acquired in 2016 is a helium recycling system CODE OF TRUSTED as well as a sequencer, for a total of 490 K€; DONATIONS COMMITEE Research team workspace reconfiguration and scientific equipment Research project financing is primarily dedicated to nervous system diseases and spinal cord trauma. Technological acquisition for 392 K€; platforms (neuroimaging, vectorology, genotyping sequencing, cell culture and histology) support these projects. On November 3, 2010, ICM Scientific IT storage capacity acquisition and calculation cluster Fundraising and communication costs (12%) represent expenses in canvassing of the general public (donations and received certification from for 737 K€. bequests) as well as companies and private foundations (patronage and sponsorship) and communication. the Comité de la Charte Fixed assets amount to 54.3 M€. On December 31 2016, cash flow amounted Operational costs (7%) represent support staff costs (finance, human resources, legal, IT and logistics). pour le Don en Confiance to 28.5 M€. ICM organization funds represent 45.7 M€. This includes equity Applications on allocated resources (7.9 M€) primarily represent company and foundation donations received (Code of Trusted of 19.3 M€ as well as investment subsidies of 26.4 M€. Nonexpendable over the course of the year, to be utilized later for specific multi-year research programs. Donations Committee), endowments total 1.2 M€. By fiscal year end, dedicated funds renewed on October 6, (to be allocated to various programs) amounted to 7.9 M€. 2016.

MONETARY RESERVE POLICY For over 20 years, ICM was supported by an 11.7 M€ grant when it was started in 2006. The the Committee has board has a very cautious policy in terms of monetary reserve been a regulator of ALLOCATION OF RESOURCES FROM THE GENERAL PUBLIC preservation. ICM reserves are invested in marketable securities (long-term professoressional investment contracts with major banks, capital guaranteed and 100% in fundraising from the RESOURCES RAISED FROM THE GENERAL PUBLIC AND USED IN 2016 TOTALED 11.9 M€. euros). general public.

IN SHORT, 71€ OF EVERY 100€ RAISED FROM THE GENERAL PUBLIC WERE USED TO FUND SOCIAL MISSIONS AND INVESTMENTS. IN-KIND VOLUNTARY CONTRIBUTIONS Its action is centered on 3 leading guidelines: 25€ WERE USED TO COVER FUNDRAISING AND COMMUNICATION COSTS, AND 4€ TO COVER ICM OPERATIONAL COSTS. Volunteering: ICM was supported by volunteering over the course of the fiscal year, especially for communication campaigns in Paris and the three certified organizations regional branches. Estimated volume is 1.4 yearly full-time equivalent, must respect ethics i.e. 37 K€ based on hourly minimum wage. regulations, must abide by collective discipline MAINTAINING A HIGH LEVEL OF EXCELLENCE IS KEY FOR ICM, WHICH IS with respect to donors, 25% SOCIAL MISSIONS AND INVESTMENT WHY THE INSTITUTE IMPLEMENTED INTERNAL AND EXTERNAL AUDITING and must accept FUNDRAISING AND COMMUNICATION COSTS 71% PROCEDURES TO ENSURE THOROUGH AND EFFICIENT continuous monitoring of OPERATIONAL COSTS MANAGEMENT: AS A MEMBER OF THE TRUSTED DONATIONS COMMITTEE commitments. AND INVOLVEMENT OF AN INDEPENDENT AUDITOR. 4%

78 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 79 DILIGENCE AND TRANSPARENCY 2016 FINANCIAL STATEMENT

ICM FOUNDATION - 2016 PROFESSORIT AND LOSS STATEMENT EXERCICE CLOS LE 31 DÉCEMBRE 2016

2016 ALLOCATION 2016 2016 OF RESOURCES 2016 RESOURCES RESOURCES APPLICATIONS RAISED FROM THE RESOURCES APPLICATIONS COLLECTED COLLECTED GENERAL PUBLIC BY AND USED APPLICATION

Carryover of resources collected from general public not allocated/used at start of fiscal year 537 606

1. Social Missions 24 856 025 8 459 725 1. Resources collected from general public 11 911 067 11 911 067 Actions directly carried out Unallocated monetary donations 10 209 784 10 209 784 Allocated monetary donations 321 800 321 800 Research Programs 13 717 879 2 279 528 Unallocated bequests and other gifts 780 983 780 983 Technological Research Platforms 6 805 363 2 818 012 Allocated bequests and other gifts 0 0 Research Application and Incubator 3 144 114 2 374 195 Other social missions 1 188 670 987 990 Other revenue from general public generosity 598 500 598 500

2. Other private funds 8 352 390 Patronage 3 127 655 Partnerships 3 149 193 2. Fundraising costs 3 736 848 2 949 528 Private subsidies 2 075 543

Cost of appeals to the generosity of the general public 3 366 891 2 642 029 Costs related to private fund canvassing 259 861 215 989 3. Subsidies and other public financial support 5 509 568 Communication costs 110 096 91 509

4. Other products 6 681 608 Financial products 442 084 Services rendered 3 268 019 3. Institute operational costs 2 258 740 501 814 Other products 2 971 505

I. TOTAL APPLICATIONS 30 851 612 11 911 067 I. TOTAL RESOURCES 32 454 633 II. PROVISIONS 16 835 II. CARRYOVER OF PROVISIONS III. PLEDGES ON ALLOCATED RESOURCES 7 859 810 III. CARRYOVER OF ALLOCATED RESOURCES UNUSED IN PREVIOUS FISCAL YEARS 7 464 986 IV. VARIATION OF ALLOCATED FUNDS COLLECTED FROM GENERAL PUBLIC -1 543 IV. FISCAL YEAR SURPLUS 1 191 362 V. INSUFFICIENT FISCAL YEAR RESOURCES V. GRAND TOTAL 39 919 619 VI. GRAND TOTAL 39 919 619 12 447 130 Share of fixed assets acquired during the fiscal year financed by collected funds Neutralization of provisions for depreciation of fixed assets financed by collected funds

TOTAL APPLICATIONS FINANCED BY FUNDS COLLECTED FROM GENERAL PUBLIC 11 911 067 TOTAL APPLICATIONS FINANCED BY FUNDS COLLECTED FROM GENERAL PUBLIC 11 911 067

BALANCE OF FUNDS COLLECTED FROM GENERAL PUBLIC NOT ALLOCATED/USED END OF FISCAL YEAR 536 063

EVALUATION OF VOLUNTARY IN-KIND DONATIONS EVALUATION OF VOLUNTARY IN-KIND DONATIONS Social missions 36 960 Volunteering 36 960 Fundraising costs In-kind services Operational costs In-kind donations Total Total

80 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 81 COMMUNICATION AND PHILANTHROPY

YOUR GENEROUS SUPPORT AND INVOLVEMENT GAVE RISE TO AN UNPRECEDENTED SCIENTIFIC ADVENTURE. TOGETHER, YOU HAVE DECIDED TO ACT ALONGSIDE US TO IMPROVE CURRENT AND FUTURE WELL-BEING FOR MILLIONS OF WOMEN AND MEN WORLDWIDE.

Le cercle des Amis de l'ICM p.84

Communication p.86

Thank You p.88

82 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 83 COMMUNICATION AND PHILANTHROPY LE CERCLE DES AMIS DE L'ICM

FUNDS RAISED FROM BEQUESTS AND LIFE INSURANCE ROSE DRAMATICALLY IN 2016, REACHING LE CERCLE DES AMIS DE L'ICM A TOTAL OF 0.8 M€. The Committee aims at rallying PHILANTHROPY TO SUPPORT RESEARCH support to help ICM bring its ON NERVOUS SYSTEM DISEASES ambition to life. Members are: MEMBERS Lily SAFRA, Le Cercle des Amis de l'ICM Honorary President Lindsay OWEN-JONES, Le Cercle des HE CIRCLE OF FRIENDS OF ICM BRINGS TOGETHER THE INSTITUTE’S MAJOR BENEFACTORS Amis de l'ICM Honorary President (INDIVIDUALS, BUSINESSES, FOUNDATIONS AND ORGANIZATIONS). SCIENTIFIC PARTNERSHIPS, Pr. Gérard SAILLANT, ICM President FINANCIAL SPONSORING, EQUIPMENT DONATIONS OR SKILL PATRONAGE: SUPPORT FROM PRIVATE Jean TODT, ICM Vice-President T Maurice LÉVY, Co-President of the Cercle PARTNERS AND THE GENERAL PUBLIC’S GENEROSITY ARE KEY IN ALLOWING ICM TO INCREASE ITS des Amis de l'ICM RESEARCH PROGRAMS, RECRUIT THE BEST SCIENTISTS, ATTRACT YOUNG TALENT AND PROVIDE THEM WITH David de ROTHSCHILD, Co-President of CUTTING-EDGE TECHNOLOGICAL EQUIPMENT. THROUGHOUT THE YEAR, PRIVATE LABORATORY VISITS ARE the Cercle des Amis de l'ICM ORGANIZED FOR CIRCLE MEMBERS AS WELL AS SCIENTIFIC AND CULTURAL CONFERENCES AND Cédric de BAILLIENCOURT, MEETINGS WITH RESEARCHERS. Jean BURELLE, Sylvain HEFES, François HENROT, Jean-Philippe HOTTINGUER, Christian SCHMIDT de la BRELIE, François THOME, IN 2016, TWO MAJOR EVENTS Isabelle WEILL, BROUGHT TOGETHER MAJOR Serge WEINBERG, ICM Treasurer BENEFACTORS IN SUPPORTING Alain WICKER ICM’S FUTURE CHALLENGES:

IN JUNE, THE INSTITUTE ORGANIZED A GALA AN ONGOING PARTNERSHIP WITH THE FIAC DINNER AT THE CONCIERGERIE, IN PARIS, CONTEMPORARY ART FAIR WITH THE “ART 1 WITH MAJOR BENEFACTORS 2 AND SCIENCE” BREAKFAST 240 guests attended a dinner hosted by Professor Marie Vidailhet, neurologist, Jennifer Stéphane Bern and took part in a recital by Flay, FIAC Director, researcher and team leader Natalie Dessay as well as a choreography by at ICM along with artists Camille Henrot, Jean- Marie-Claude Pietragalla and Julien Derouault, Sébastien Leblond-Duniach, countertenor accompanied at the piano by Philippe Cassard. Sébastien Fournier and choreographer Florence After dinner, an art and exceptional experiences Guérin shared their vision of movement disorder auction was held, hosted by auctioneer Frédéric with the Institute’s Founding Members and Chambre (PIASA). Thanks to the generous sup- event host Claire Chazal. Over 300,000€ port of the attendees, 1.2 million € were raised were raised over the course of the morning to over the course of the evening for ICM. support ICM research.

84 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 85 COMMUNICATION AND PHILANTHROPY COMMUNICATION THEY SUPPORTED ICM FEE RARISSIME LE LIONS CLUB DES ESSARTS-LE-ROI 20 KM DE PARIS YOUR SUPPORT IS ESSENTIAL LIONS CLUB BLOIS DOYEN LIONS CLUB BLOIS RENAISSANCE DELIA LIONS CLUB CLASSIC DAYS SEVERAL EVENTS TOOK PLACE DURING THIS PAST YEAR ALREADY FILLED LIONS CLUB CHAMBORD DE VERRIÈRES LE BUISSON UN CHRONO POUR UN DON GÉRARD CROTTI FERBLANC FUNDRAISING WITH EXCITING SCIENTIFIC PROGRESS. MUSIC PASSION COGNO-BOURDIEU PIERRE MOREL LORS DU TOUR AUTO PARKINSON ECOLE SAINT JEAN DE PASSY Un circuit pour le cerveau JACQUES-NICOLAS DE WECK POUR FÉDÉRATION FRANÇAISE POUR LE DON DE SANG BÉNÉVOLE DE ST MAUR LIONS CLUB DE MONTLERRY SOGNO DI ET LE ROTARY CLUB DE SAINT MAUR Porsche Club Motorsport Lions Club Lyon Doyen CAVALLINO Internationaux de Strasbourg mong these was the tenth “Future Research” program Agraduation ceremony; “The Brain to Market” Summer School combining neuroscience and entrepreneurship on the topic of epilepsy, and the Dublin presentation of “The Move” program, REGIONAL DELEGATIONS that uses miming to teach neurological ICM researchers collaborate with several regional semiology to medical school students. teams. Shared research projects are focused on three illnesses: Frontotemporal lobar degeneration Various communication efforts were (FTLD) in Caen (Basse-Normandie), Amyotrophic carried out during the National Lateral Sclerosis in Limoges (Limousin), and spinal Neurodegenerative Illnesses Days, The IDEC Maxi Trimaran, cord damage in Clermont-Ferrand (Auvergne). both towards Institute donors and ICM partner, aiming the general public. These efforts were for the Jules Verne Trophy an opportunity to cement ICM’s role as a major player in nervous system diseases research and position it as a key contact for media inquiries. ICM ON THE OUTSIDE “ICM’s vision has always meant a lot to me. One day, we will lean the brain’s secrets thanks to the hard work of women and men who are dedicated to F.P Journe renewed its commitment to « MENTAL DÉSORDRE » gaining a deeper understanding of neuroscience and donate 5% of proceeds on each sale of À LA CITÉ DES SCIENCES ET DE L’INDUSTRIE to furthering medicine. I am proud to have supported the Centigraphe Souverain Watch to ICM. CHARITY DAY BGC 20KM DE PARIS ICM from the start with the yearly planning of the « 48H POUR FAIRE VIVRE DES IDÉES » 20 KM de Paris, with a booth in the race village, IDEC has chosen to display LE MAXI TRIMARAN IDEC À LA CONQUÊTE an annual donation as well as complimentary race ICM logo on its Maxi Trimaran DU TROPHÉE JULES VERNE bibs for researchers. ICM’s mission is innovative and TROPHÉE LES ECHOS ambitious: it deserves all the support possible not COURSE DES HÉROS only for research, but also to improve patient care and S3ODÉON everyday life. Congratulations to the whole team for « MUSIQUE & CERVEAU » this unparalleled human and scientific adventure.”

VIVA TECHNOLOGY DIDIER ECK SEMAINE DU CERVEAU President of the 20 KM de Paris Association COLÈRES PLANQUÉES TOUR DU LAC DE VASSIVIÈRE

86 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 87 COMMUNICATION AND PHILANTHROPY THANK YOU

Marcel Dupuis SODEXO Anne et Raymond Bert Claude Félix SOLIDAIR'S Gérard Bertinetti FERBLANC FUNDRAISING Jean-Cyril Spinetta BIOCODEX Emilio Ferré Yannick Tarondeau Jean-Claude Biver FINETFO SA Jean-Philippe Thierry Alain et Blandine Bizot FONDATION AIR LIQUIDE François Thomé Gaby Blum FONDATION MARIE-ANGE BOUVET Albert Uderzo BMENERGIE LABRUYERE Thierry Varène M. et Mme André Bohm FONDS PATRICK DE BROU DE LAURIERE Antoine Virgili Hubert Boinet Dimitri et Maryvonne Fotiadi Dominique Vizcaino Tatiana et Adrien de Boisanger Marie-Pierre Fournier YVES ROCHER M. et Mme Philippe Boitet Jean-René Fourtou Famille Yoël Zaoui Chantal Bolloré GROUPE G7 15 anonymous M. et Mme Michel Yves Bolloré GALORI TRUST Irène Bonnet GIULIANI S.p.A Jean-Marie Borzeix GLAXO SMITH KLINE DONATORS Francis Bossu Mina Gondler Yves Boucheny THANK YOU GROUPE EMERIGE Benoit Abdelatif Monique Bourven GROUPE LUCIEN BARRIERE Pascal Abensour M. et Mme Thierry Bourvis GROUPE PREVOIR ACCURACY Jean Bousquet Monique Guérinat et FISA ALAIR & AVD Claude Bouygues MAJOR PATRONS M. et Mme Jacques Garaialde BANQUE PICTET Mireille et René Hadjadje Colette Amram Renaud Bouygues GROUPE PASTEUR MUTUALITE Anne Bardinon Pierre Hanriot Marie-José Alfandari Jean-Jacques Branger Maria Rosa Bemberg GROUPE IDEC Jean-Paul Baudecroux Jean-Marie et Laurence Hennes M. et Mme Emmanuel Allard François Brière CARCEPT PREV – IPRIAC - KLESIA Sylvain et Michèle Héfès BGC PARTNERS HUMANIS Jean-Luc Allavena M. et Mme Jean-Jacques Brunet FIA FOUNDATION FOR THE AUTOMOBILE François Henrot Gérard Bertinetti IWC SCHAFFHAUSEN Benoît André Famille Bucaille AND SOCIETY M. et Mme Alain Joly Christian et Marie-Claire Blanckaert LILLY Philippe André M. et Mme Etienne Burdin FONDATION BETTENCOURT SCHUELLER Serge Kampf Marie-Claire Blanckaert Marie-Jeannine Jacobson Christine André Jean et Anne-Marie Burelle FONDATION EDF DIVERSITERRE Christiane Laborie et Roger Lionnet M. et Mme Pascal Boileau Alain Kahn ARTEMIS Dr André Buyse FP JOURNE - INVENIT ET FECIT Maurice Lévy BOLLORé M. et Mme François Lafon ARB CONSEIL SAS M. et Mme Alain Candelier FONDATION E. J. SAFRA Dominique et Danièle Mars BOREL & BARBEY Bernard Lange ASSOCIATION JEAN-CLAUDE DUSSE François Canellas HSBC France Richard Mille Irène Bonnet ASSOCIATION MUSIC PASSION PARKIN- Bertand Lavier Marie-Noëlle Canu-Duclert Lily Safra ORACLE Micheline Bridel SON LES AMIS DE CAPUCINE M. et Mme Arnaud Caspar Docteur Léone Noëlle Meyer PATHé Famille Bucaille ASSOCIATION PAUL ET PHILIPPE PERROT Martin Lebeuf CB RICHARD ELLIS OCIRP PHILIPPE FOUNDATION, INC. Jean et Anne-Marie Burelle ASSOCIATION SOGNO DI CAVALLINO Angélique Lenain et Fabrice de Gaudemar CELIO ORRICK RAMBAUD MARTEL RATP Louis Camilleri ASSOCIATION SPORTIVE ET CULTURELLE LIGUE DE FOOTBALL ProfessorESSION- CHAMPAGNE LAURENT-PERRIER Lindsay Owen-Jones David de Rothschild CAMPENON BERNARD CONSTRUCTION DE L'AIR NEL MOET & CHANDON PUBLICIS SCHNEIDER ELECTRIC CAPGEMINI ASSOCIATION VIVRE A SAINT DAMIEN Georges Louviot Jean-Bernard Champeau RACE OF CHAMPIONS Claude Sfeir Marella Caracciolo Agnelli Jean-Pierre Aubin Florent Menegaux Patrick Charpentier Edouard et Martine de Royère Jean Todt et Michelle Yeoh P. et J.P. Carle Aurel BGC M. et Mme Bertrand Meunier Suzanne Charpentier Michael Schumacher Serge Weinberg Olivier Carre AUTOMOBILE CLUB DE FRANCE Eric et Hervé Neubauer Didier Chartier 1 anonymous 1 anonymous Patrick Charpentier M. et Mme Guy Autran Novalis Pr Christian Chatelain Suzanne Charpentier Nicole Ayanian Schneider Gilles et Sylvie Pélisson Amaury et Alix de Chaumont Quitry MAJOR BENEFACTORS BENEFACTORS M. et Mme Léon Cligman Solange Bakalowicz Jean-Luc Petithuguenin Dominique Chedal COMITE NATIONAL OLYMPIQUE BANQUE DE LUXEMBOURG PHILIP MORRIS INTERNATIONAL Jean-Loup Cherel AIR FRANCE Benoit Abdelatif – Classic Days ET SPORTIF FRANCAIS Frédéric Banzet Jacques Popper Dr André Chérot Famille Jan Aron ACCOR CREDIT AGRICOLE D'ILE-DE-FRANCE M. et Mme Pierre-René Bardin Christian Poquet Brigitte Chichignoud Elisabeth Badinter AMAURY MEDIAS MECENAT M. et Mme Rémy Baschet Claude et Benoît Potier Prince et Princesse de Chimay Luc Besson Christine André CREDIT MUTUEL NORD EUROPE Laurent Baud/TECHNOMARK RELAIS & CHATEAUX Fabien Chone BOUYGUES Yvon André et Annette Gellé CREPA RETRAITE M. et Mme Claude Baudon Lucienne Collin ASSOCIATION DEMAIN DEBOUT Jean-Patrice et Marie-Anne Dalem Jean Reno M. et Mme Thierry Benderitter Philippe Clément FEDERATION FRANCAISE DU SPORT ASSOCIATION RMC BFM M. et Mme Laurent Dassault Jean-Paul Ringeard M. et Mme Arnaud Benoist Jean-François Colin AUTOMOBILE ASSOCIATION SOGNO DI CAVALLINO DAVID HERRO TRUST ROTHSCHILD & CIE BANQUE Robert Bensoussan Gérard Collet FONDATION AREVA ASSOCIATION SPORTIVE ET CULTURELLE Claude Demole Nelly Rouyrès Fernande Benveniste Bertrand Collomb FONDATION ARPE DE L'AIR Aline Derbesse RSI ProfessorESSIONS LIBERALES ET Gérard Bequin Alberto Colussi FONDATION COGNACQ-JAY M. et Mme Guy Autran Jean-Louis et Marie-Cécile Dufloux ARTISANS Claude Berda COMBATTRE LA PARALYSIE FONDATION D’ENTREPRISE MICHELIN AXA RESEARCH FUND Michel Duhoux Hubert Saltiel BERNARD MIRABAUD ENERGIE Françoise de Combret FONDS DE DOTATION PIERRE BERGE AXERIA PREVOYANCE Rena et Jean-Louis Dumas Guy Savoy M. et Mme Jacques Bernier COTY INC.

88 ICM ANNUAL REPORT 2016 ICM ANNUAL REPORT 2016 89 COMMUNICATION AND PHILANTHROPY THANK YOU

Mme Dominique Coulon-Temkine DOYEN M. et Mme Antoine Labbé Georges-Michel Mouries Bruno Roger M. et Mme Gilbert Vidal M. et Mme Robert Counoy FRANCE GALOP LABORATOIRE ECLAIR Renée Mullie ROMEO SA Corinne et Ramon Villagrasa Charlie Coutouly M.et Mme Fredouille Michel Labouret Jean Claude Muret Patrick Roque M. et Mme Guillaume Vincenot CREDIT AGRICOLE CENTRE OUEST Patrick Fuchs Jean-François Labrousse Isabelle Murray Jean-Jacques Rosa VINCI CONCESSIONS CREDIT MUTUEL NORD EUROPE GAGNERAUD PÈRE & FILS M. et Mme Michel Lacoste Yves Néron-Bancel Martin Rosdy Gérard Viquel Françoise Crouzet André Gaubert Réjane et Michel Lacoste NEUROLIGUE ROTARY CLUB ORLEANS VALDELOIRE Antoine Virgili Jean-Patrice et Marie-Anne Dalem Bernard et Denise Galambaud M. et Mme Etienne Lafon Jack Noirtin ROTARY CLUB TOULOUSE SUD Olimpia Weiller Olivier Dassault Jeanne Galli Pauline Lamonica NOVARTIS Richard Roth M. et Mme Wierre Laurent Dassault GALOA Bernard Lange Nahed Ojjeh Elisabeth de Rothschild Charles Moore Wilson Jean-Luc Davesne M. et Mme Gilles Gantois Christian Langlois-Meurinne Jacques Olivier Louise de Rothschild Brigitte Wolff Vicomte Olivier Davignon Philippe Genève Jacques Larcher ONDRA PARTNERS M. et Mme Bernard Rouer XO EDITIONS M. et Mme Jean de Balquet du Chayla Marie-France Geoffroy FONDS PATRICK DE BROU DE LAURIERE Jérôme Paris Thierry Roussel ZENITHOPTIMEDIA Charles de Boisriou Francis Thomas Gleeson Philippe Lassus René Pascal Nelly Rouyrès Gérard Zimmerlin Christiane de Cherisey GLG Partners Alain Lazimi David Pastel M. et Mme Ruckstuhl Vanessa Von Zitzewitz M. et Mme Philippe Déboudé Christian Gloz LE CHEVAL FRANÇAIS Philippe Pataud Igor Rybakow 75 anonymous Annette Decroix Lavaur Alain Goffi Martin Lebeuf Guy Paucot Jean-Pierre Sabardu Famille Dehove JeanFrançois et Dominique Gouédard Anne Le Lorier Daniel Payan Hubert Saltiel Guy Delarue M. et Mme Pierre-Henri Gourgeon Bernard Lefebvre M. et Mme Claude Peaudeau Claire Sarti Ghislaine Delattre Allan Green Patrick Lefort Valérie Pécresse Guy Savoy Jean-Louis Delvaux GROUPE BABILOU Angélique Lenain et Fabrice de Gaudemar Claude Pequart Patrick Sayer Micheline Deschamps GROUPE LHOIST LES VOILES DE SAINT BARTHE Guy Percie du Sert M. et Mme Christian Schlumberger M. et Mme Patrice Diehl Jérôme Guerrand-Hermès Maurice Lesaffre Jacques Pericchi M. et Mme Pierre Schule Danielle Dubuit Pierre Guichet Haim Leshanot Michel Pernot Colette Schumacher ICM volunteers Jean-Louis et Marie-Cécile Dufloux Catherine Guillouard Nicolas Lescure Jacques Perrin Claude Schweisguth Jean-Philippe Dugue Vivien de Gunzburg Jean-Jacques Lestrade Jean Peter SICA2M Antonio Lopez Jacques Dumas Christian Haas Hubert et Catherine Lévy-Lambert Laurent Pétin SFR Annie Wilson M. et Mme Claude Dumas Pilhou Mireille et René Hadjadje LIONS CLUB DES ESSARTS Jean-Luc Petithuguenin François Silvestre de Sacy Nicole Fourn Michel Dupuis Marc Haeberlin Jacques et Irène Lombard ORKYN' Gérard Simmat Ariane Bucaille Marcel Dupuis Maria Halphen Marie-Thérèse Lombard M. et Mme Patrice Piccon SOCAUSUD Marie-Claude Theguel Henri Dura M. et Mme Thierry Hannecart L’Oréal Luciano Pietropoli SOPAREXO Pascale des Abbayes Cécile et Christophe Durand-Ruel Pierre Hanriot Francis Lotigie-Browaeys Yves Piguet Ruinet SOLIDAIR'S Mohamed El Babsiri Bob Harifin Daniel Louppe Janine Pion-Goureau SORIN GROUP M. et Mme Claude Elmaleh Maryse Hasselmann-Gérard M. et Mme Yves Loussouarn Dominique Pion-Goureau Claudine Soubrie EMERAUDE INTERNATIONAL Gérard Haution Claudine Luciani Caroline et Olivier Plantefève Marc Soulé ERIC HOLDING Jean-Claude Heili M. et Mme Pierre Magnant PMU SPEB GROUPE EMERIGE Camille Henrot Marie France Malezieux Blicq M. et Mme Henri de Ponnat SPEBI Gérard Erstein Alice Henry-Mairiniac Hugues et Jocelyne Mallet POTEL & CHABOT SA Eric Spielrein Jacques-Arthur Essebag Paul Hermelin Bob Manoukian Benoît Potier Giuliana Spotorno EXELGYN SA Brigitte Hidden François Manset Philippe Pourchet STADE FRANCE Eliane Exbrayat Violette Hirsch Gilles de Margerie PRODUCTION ET MARCHÉS Henry Stanislas Olivier et Nathalie Favre M. et Mme Bernard Hours M. et Mme Hervé Margolis Jean de Quatrebarbes M. et Mme Vincent Strauss Amélie Fayet HUNTINGTON ESPOIR OUEST Monsieur Marinopoulos Bernard Quetier Alain Tachot FEDERATION FRANCAISE DE TENNIS Jean-Pierre Hutin M. et Mme Patrick Martin-Michaud Jean-Paul Rabache Claude Taittinger FEDEX CORP Eve Icole Pierre Martinet Françoise Rabouin Yannick Tarondeau Claude Félix IMPALA SAS Bruno Matheu Paul Raingold Henri de Termont FINANCIERE DE L'ECHIQUIER M. et Mme Jean Iribarren Yves Mathieu M. et Mme Patrick Rannou Pascal Tetard FINANCIERE POCH Robert Jamain Bernard Maurel Alain Ranval Alain Thinot FERBLANC FUNDRAISING Christophe Karvelis Senn Florent Menegaux Alain Rauscher Docteur Martine Thomassin Roland Fernet Pierre Jardinier Philippe Meignan M. et Mme Jean-Pierre Raynal TRACE ONE Charles-Henri Filippi JEAN ACHE S.A. Alain Menoncin Christian Revol Janine Tristant Jean-Claude Meyer Alain Kahn MILLE MERCIS Laurent Richier Nicolas de Turckheim Thierry Flecchia Michael Kennedy Thierry et Natacha Millemann RICOL, LASTEYRIE & ASSOCIES M. et Mme Guy Ullens Jean Floresco Cyril Kongo François Momboisse Philippe Rincazaux Isabelle Valeani-Portes Fondation Plenum Daniel Kouzo Maÿlis de Montgolfier Jacques et Annie Riou Edith Vansteenberghe FONDATION VENTE PRIVEE Sophie et Frédéric Krebs Gérald Mourand Christine Rivet Thierry Varène Philippe Foriel-Destezet M. et Mme Pierre Kuhn Bernard Moreau Simon Robertson Patrick Vegeais FONDS DE DOTATION LIONS CLUB LYON M. et Mme Patrice de Laage de Meux Daniel Moreau Aldo Robotti VERTU

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