2020 ANNUAL REPORT

TABLE OF EDITORIAL 10 YEARS OF PROGRESS CONTENTS & INNOVATION • Paris Brain Institute, a revolutionary model to accelerate the fight against brain diseases .p8 • Highlights 2020 .p10 • Our research team’s achievements .p13 • Key Figures .p14

RESEARCH • 2020, a year filled with scientific breakthroughs.p16 • Cutting-edge technological platforms .p26 • IHU, Paris Institute of Translational Neuroscience .p30 • Paris Brain Institute teams .p32 • Internationnal partnerships .p34

CLINICAL RESEARCH AND CARE • COVID-19 Pandemic : the Institute’s clinical forces unite .p36 • The Clinical Investigation Center works towards tailored treatment for each patient .p38

INNOVATION AND KNOWLEDGE TRANSFER • Research applications .p40 • Open Brain School .p44

PARIS BRAIN INSTITUTE • Human resources .p46 • Governance .p48 • Financial report .p51 • Communications and Development .p56 © Inserm/Dournaud, Pascal. Groupe Publicis. Mathieu Génon. Jimmy Delpire. Bioserenity. Guillaume Miquel. • Thank You .p60 Nicolas Renier. Théo Ribierre. Alexandre Bône. John Bersi. Julien Pigeon. Jean-Philippe Pariente. ” AS WE LOOK BACK ON THE DESPITE CONTINUING UNCERTAINTIES, WE

YEAR 2020, WE MUST FIRST THINK HAVE CONTINUED TO EVOLVE AND GROW. DESPITE THE PANDEMIC, THE INSTITUTE UPHELD A

OF ALL THOSE WHO HAVE BEEN THE CHEVALERET CAMPUS, AN INCUBATOR REMARKABLE RESEARCH DYNAMIC IN 2020 WITH DEDICATED TO MEDICAL TECHNOLOGIES AFFECTED, ARE STILL AFFECTED CONTINUED SUCCESS, INCLUDING THE RECRUITMENT AND ARTIFICIAL INTELLIGENCE, WHICH OR HAVE DISAPPEARED BECAUSE OF SEVERAL RESEARCHERS, AWARDS, AND HIGHLY OF COVID-19. WE HAVE ALL BEEN WILL OPEN IN 2021, PROMISES GREAT COMPETITIVE FUNDING INCLUDING OUR 15TH ERC AFFECTED PHYSICALLY, SOCIALLY AND SUCCESS; THE GREATER INTEGRATION (EUROPEAN RESEARCH COUNCIL) GRANT. THIS OF THE PARIS BRAIN INSTITUTE IN THE ECONOMICALLY. IN THIS DIFFICULT YEAR ALSO SAW AN UNPARALLELED NUMBER OF VARIOUS ASPECTS OF CLINICAL RESEARCH, PERIOD, THE PARIS BRAIN INSTITUTE PUBLICATIONS FROM OUR RESEARCHERS IN TOP IN CLOSE COLLABORATION WITH THE HAS SHOWN A FANTASTIC CAPACITY SCIENTIFIC AND MEDICAL JOURNALS. THIS IS A DIRECT MEDICAL-UNIVERSITY DEPARTMENT FOR ADAPTABILITY, FLEXIBILITY OF NEUROSCIENCES AT THE PITIÉ- RESULT OF AMBITIOUS AND HIGH-RISK PROJECTS AND REACTIVITY. TOWARDS THE SALPÊTRIÈRE HOSPITAL; THE PURSUIT OF LAUNCHED 3 TO 5 YEARS AGO THAT ARE COMING TO HOSPITAL, WITH THE MOBILISATION OF HIGH-LEVEL RESEARCH ON NEUROLOGICAL FRUITION. HUMAN AND MATERIAL RESOURCES; AND PSYCHIATRIC DISEASES, BUT ALSO THE INSTITUTE WAS ALSO INVOLVED IN RESEARCH TOWARDS ITS STAFF, TO GUARANTEE ON THE FUNDAMENTAL UNDERSTANDING ON COVID-19 WITH THE LAUNCH OF THE COVID THEIR SAFETY AND TO DEVELOP OF THE BRAIN IN NORMAL CONDITIONS, NEUROSCIENCE COHORT TO STUDY NEUROLOGICAL SALIVARY TESTS TO DETECT COVID-19; THE PROGRESSION OF ARTIFICIAL AND PSYCHIATRIC CONSEQUENCES OF SARS-COV-2 TOWARDS SCIENCE, BY DEVELOPING INTELLIGENCE AND THE IMPROVEMENT OF INFECTION. NEW RESEARCH SUCH AS THE COVID COGNITIVE CAPACITIES. NEUROSCIENCE COHORT TO MONITOR

I WOULD LIKE TO TAKE A MOMENT TO ACKNOWLEDGE THE NEUROLOGICAL AND PSYCHIATRIC I WOULD LIKE TO THANK YOU, PARTNERS, PROF JEAN-YVES DELATTRE, OUR INSTITUTE’S CONSEQUENCES OF COVID-19, AND DONORS AND VOLUNTEERS, FOR YOUR MEDICAL DIRECTOR AND DIRECTOR OF THE MEDICAL- BY CONTINUING ITS WORK ON THE INVOLVEMENT AND YOUR UNFAILING UNIVERSITY NEUROSCIENCE DEPARTMENT AT NERVOUS SYSTEM, MAINTAINING SUPPORT FOR THE PARIS BRAIN INSTITUTE PITIÉ-SALPÊTRIÈRE AP-HP HOSPITAL, WHO RETIRED A HIGH LEVEL OF SCIENTIFIC IN THIS VERY SPECIAL CONTEXT. THE LAST NOVEMBER. HIS RETIREMENT WAS A VERY PUBLICATIONS. RESEARCH CARRIED OUT HERE IS ONLY ” IN THE FACE OF COVID-19, THE ENTIRE PARIS Prof. Gérard Saillant, TOUCHING MOMENT FOR THE INSTITUTE COMMUNITY, POSSIBLE THANKS TO THE MOBILISATION BRAIN INSTITUTE COMMUNITY HAS PROVEN ITS President of AND A TRIBUTE TO HIS CONCERN FOR HUMANKIND OF EVERYONE. ” STRENGTH, ABILITY TO DESIGN NEW APPROACHES, Paris Brain Institute AND HIS EXCEPTIONAL INVOLVEMENT. PROF NEW PROJECTS, LEADING TO MANY SCIENTIFIC CATHERINE LUBETZKI IS TAKING OVER TO CONTINUE BREAKTHROUGHS. ALTHOUGH THE PANDEMIC IS OUR ACTIONS TO REINFORCE THE RELATIONSHIP NOWHERE NEAR OVER, I AM CONFIDENT THAT IT BETWEEN OUR INSTITUTE AND CLINICAL UNITS AT THE REINFORCED OUR COLLECTIVE VALUES AND THAT HOSPITAL. PATIENTS ARE TRULY AT THE HEART OF ” THE COVID-19 PANDEMIC RADICALLY CHANGED OUR PROFESSIONAL LIVES THESE HAVE BECOME A MAJOR STRENGTH FOR OUR RESEARCH. AND FORCED US TO REINVENT THE WAY WE WORK. OUR MODEL AND THE THE INSTITUTE. “SAFETY”, “ANTICIPATION” AND

STRENUOUS FLEXIBILITY WE APPLY ON A DAY-TO-DAY BASIS HAVE PROVEN “CONTINUITY” HAVE BEEN OUR KEYWORDS IN THIS WE KNOW THAT THE NEXT FEW MONTHS WILL REMAIN THEIR STRENGTHS IN THIS TIME AND ALLOWED US TO MAINTAIN A HIGH CRISIS SINCE DAY ONE. THANKS TO THE SUPPORT UNCERTAIN AS WE WAIT FOR VACCINATION LEVELS LEVEL OF EFFICACY. THROUGH COLLABORATION, PERMANENT AND FLEXIBLE OF OUR IT TEAMS, WE ADAPTED TO THE SITUATION TO RISE. IN ADDITION TO PROTECTING HEALTH AND COMMUNICATION AND HIGH STANDARDS, WE WERE ABLE TO ENSURE THAT PROMPTLY TO ENABLE WORKING FROM HOME AS WELL-BEING, WE MUST ALSO PROTECT OUR RESEARCH EVERYONE CONTINUED TO WORK IN THE BEST CONDITIONS. FOR TEAMS TO MUCH AS POSSIBLE. WORKING CONDITIONS ON-SITE DYNAMIC. DEVELOPING NEW COLLABORATIONS AND DEDICATE THEMSELVES FULLY TO RESEARCH, WITH LIMITED ADMINISTRATIVE WERE ALSO ADAPTED AND MADE SAFE WITH THE INTERDISCIPLINARY APPROACHES, GROUNDBREAKING CONSTRAINTS. FOR PLATFORMS TO ENSURE OPTIMAL SERVICE AND SUPPORT SUPPORT OF OUR LOGISTICS TEAMS AND RESPECTED PROJECTS ON THE NERVOUS SYSTEM AND TEAMS WHILE DEVELOPING THEIR ORGANIZATION. FOR SUPPORT TEAMS PHYSICAL DISTANCING BY EACH AND EVERY ONE ITS PATHOLOGIES, AND INVESTING IN NOVEL TO REMAIN AS OPEN AS POSSIBLE TO RESEARCH TEAMS WHILE MAKING OF US AT THE INSTITUTE. THE INSTITUTE ALSO TECHNOLOGY DEVELOPMENT REMAIN ABSOLUTELY SURE THAT WE FOLLOW THE NECESSARY RULES FOR THE SITUATION. THE IMPLEMENTED AND CARRIED OUT COVID-19 SALIVA ESSENTIAL. MEDICAL RESEARCH MUST REMAIN A INVOLVEMENT OF THE ENTIRE INSTITUTE COMMUNITY IS WHAT HAS MADE PCR TESTS ON A VOLUNTARY AND ANONYMOUS BASIS PRIORITY FOR SOCIETY, AND WE HAVE AN A MAJOR SUCCESS POSSIBLE TODAY AND WILL GUARANTEE THE SUCCESS OF FUTURE FOR INSTITUTE PERSONNEL, TO ENSURE OUR STAFF’S ROLE TO PLAY. ” ORGANIZATIONAL AND SCIENTIFIC PROJECTS AS WELL. ” SAFETY.

Corinne Fortin, Prof. Alexis Brice, Secretary General of Paris Brain Institute Executive Director of Paris Brain Institute 6 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT A decade of progress and innovations ICM receives state certification as part of the ICM’s funding ”French Tech Seed” fund managed by Bpifrance. is renewed and This certification confirms the dynamic strategy supplemented for PARIS BRAIN INSTITUTE, implemented by the iPEPS bio-incubator to promote the IHU program. entrepreneurship with strong expertise in the fields of A REVOLUTIONARY MODEL neurology and psychiatry. 2019 TO ACCELERATE THE FIGHT Identification of compensation 2018 mechanisms in Alzheimer’s disease with the INSIGHT cohort of elderly subjects by Professor Bruno Dubois’s Open Brain AGAINST BRAIN (AP-HP, Sorbonne Université) team School DISEASES with Pitié-Salpêtrière Hospital. PARIS Paris Brain Institute launches its training center, Open Brain School, to share neuroscience knowledge and strengthen training for future researchers and doctors on a national and international level. PARIS BRAIN INSTITUTE WAS BUILT ON THE INVOLVEMENT OF CELEBRITIES AND PUBLIC INSTITUTIONS WITH A SHARED GOAL : UNDERSTANDING THE 2017 BRAIN AND TREATING NEUROLOGICAL Creation of the AND PSYCHIATRIC ILLNESS. Neuroinformatics Center for cutting-edge research and medicine.

2003 - 2010

An idea turns into a project, driven by hope and motivation ! Thanks to the founding members, donors and public stakeholders, the Institute comes to life: in 2020, the Paris Brain Institute building was inaugurated within Pitié-Salpêtrière Hospital in Paris. 2011 Development of a new 2016 imaging technique to visualize The Clinical Investigation Center (AP-HP, remyelination in patients with Inserm) opens its doors to patients taking multiple sclerosis, impossible part in clinical trials within the Institute. to see with classic imaging 2014 techniques. Obtaining the Carnot label, to accelerate the development of new Acquisition and operation technologies in the fields of neurology and psychiatry of a PET-MRI with AP-HP, the first in France with both Along with its institutional clinical and research use. 2015 partners, the Institute 2012 receives certification as a “Center for excellence in ICM becomes one of 6 centers for scientific neurodegenerative diseases” and medical excellence supported by the as part of a national program on Investments in the Future project implemented Bioserenity, a startup incubated at Paris neurodegenerative diseases. by the Ministry of Higher Education and Brain Institute, designs the Neuronaut : Research and the Ministry of Health (IHU). smart clothing for at-home care and monitoring of patients with epilepsy.Today, Bioserenity has Inauguration of iPEPS-ICM, the over 500 employees worldwide. The company first startup incubator dedicated to is part of the Next 40, an index created by the nervous system diseases. French government in 2019 to track the 40 8 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 9 French start-ups with very high potential. A decade of progress and innovations PANDÉMIE DE COVID-19 : NATIONAL L’INSTITUT DU CERVEAU AWARENESS CAMPAIGN SE MOBILISE ET AVANCE #VOTRECERVEAUVOUSRENDREMARQUABLE

To support its recent name change, Paris Brain Institute launched a national awareness poster campaign entitled #votrecerveauvousrendremarquable (“your brain makes you remarkable”), produced pro bono IN by historical partners Publicis and JCDecaux.

Through portraits of great personalities from the politics, sports, culture and the arts including Simone Veil, Rafael Nadal, and Jean Reno, and a slogan filled with meaning, this campaign aims to make each of us aware of the vital importance of this fascinating organ, the most complex in the human body.

PARIS BRAIN INSTITUTE CELEBRATES Professor Jean-Yves Delattre, Director of the Medical 2020 THE EXCEPTIONAL INVOLVEMENT OF University Neuroscience Department and former Medical Director of Paris Brain Institute, retired in November 2020. PROFESSOR JEAN-YVES DELATTRE The entire Paris Brain Institute teams thank Professor Jean- AND THE ARRIVAL OF PROFESSOR Yves Delattre for his exceptional commitment and recognize CATHERINE LUBETZKI his remarkable career at patients’ bedsides. Professor Jean-Yves Delattre is replaced in these positions by Professor Catherine Lubetzki (AP-HP/Sorbonne Université).

COVID-19 PANDEMIC : PARIS PARIS BRAIN INSTITUTE’S CARNOT BRAIN INSITUTE CONTINUES CERTIFICATION RENEWED TO MOVE FORWARD FOR 4 YEARS ” I AM HAPPY TO HAVE WORKED WITH THE TEAMS AT PARIS As you will discover throughout this report, Carnot certification is a French certification BRAIN INSTITUTE. I THINK IT’S in the context of the COVID-19 pandemic, created in 2006 with the aim of developing re- A WONDERFUL INSTITUTION, A Paris Brain Institute has made every effort search partnerships between public laboratories TREMENDOUS OPPORTUNITY FOR THE to continue its research activity as best as and economic players (mainly companies). The UNIVERSITY MEDICAL NEUROSCIENCE possible and has actively participated in Ministry of research awards this certification to DEPARTMENT. OUR RELATIONSHIPS the fight against the virus and in helping Carnot institutes following a very selective call ARE STRONG, OUR DIFFERENCES those affected by it. for applications. MAKE US RICHER. I WISH GOOD

The renewal of our Carnot certification for 4 years LUCK AND MUCH SUCCESS TO PROF. From the start of the pandemic, Paris Brain ” IT IS AN HONOR FOR ME TO REPLACE will allow us to fund Carnot Maturation projects, CATHERINE LUBETZKI, MY TRAVELING Institute was in close contact with the me- JEAN-YVES DELATTRE, A LONGTIME COMPANION AT PITIÉ-SALPÊTRIÈRE dical teams at Pitié-Salpêtrière Hospital the Skills Build-up program, Carnot Training and FRIEND, FOR WHOM I HAVE SUCH ESTEEM HOSPITAL FOR DECADES, WHO HAS (AP-HP) and made equipment, goods, and scientific resourcing actions including the organi- AND AFFECTION. AS A CONTINUATION expertise available. All clinicians working zation of conferences at Paris Brain Institute, editor ALL THE QUALITIES NEEDED TO HELP OF HIS ACTIONS, I HOPE TO PROMOTE at Paris Brain Institute and in the hospital’s days, and more. THE INSTITUTE ACCOMPLISH ITS INTERACTIONS BETWEEN CAREGIVERS university medical neuroscience depart- MISSION TO ”SEARCH,­ FIND, CURE” ! ” AND RESEARCHERS, AND DEVELOP ment are on board to support the medical teams caring for patients with COVID-19. CLINICAL RESEARCH IN CONNECTION WITH Prof. Jean-Yves Delattre FUNDAMENTAL RESEARCH. ” Prof. Catherine Lubetzki

10 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 11 ADIÓS CORONA, THE WEBSITE THE MEDTECH GENERATOR & THAT DECODES INFORMATION ACCELERATOR PROJECT REPRESENTED OUR ON COVID-19 BY IPEPS, RECIPIENT OF THE SIA/ FUTURE INVESTMENT CALL FOR RESEARCH TEAM’S It can be difficult to find the right information in real time regarding the pandemic we are currently PROJECTS experiencing. That’s why a team of scientists, and notably ACHIEVEMENTS several researchers from Paris Brain Institute including This consortium, led by Paris Brain Institute, Institut Claire Wyart (Inserm), designed a website that analyzes Imagine, Institut de la Vision and Institut Pasteur, aims publications on COVID-19 and gives advice on proper at developing innovative support programs to accele- collective behavior to stop the spread of the virus. rate growth and development of startups specializing EXCELLENT RESULTS in health and artificial intelligence in the field of neu- FROM THE ANR GENERIC CALL rosciences, genetics, and rare diseases. PRESTIGIOUS AWARDS FOR PROPOSALS Public funding will be provided by the Future Investment Program (PIA) over the first two years. This announce- Every year, the generic call for proposals from the ANR CURE-ND - A UNIFIED ment marks the Institute’s desire to combine research (National Research Agency) funds research by various RESPONDE TO with innovative projects to increase discoveries to benefit players in the scientific community. This very competitive NEURODEGENERATIVE patients, in particular through its iPEPS - The Healthtech call for projects rewards innovative projects according to Hub incubator. four categories : DISEASES • JCJC : Young researcher ; A new alliance, CURE-ND, was launched • PRC : Collaborative research project ; at the end of 2020. It brings together four • PRCE : Collaborative research project – Company ; highly recognized European partners in • PRCI : Collaborative research project - International neurodegenerative diseases: DRI in Great Britain, VIB in Belgium, DZNE in Germany Mathias Pessiglione Alberto Bacci (Inserm) This year, 16 projects by researchers from Paris and our Institute. A first launch event was (Inserm) Camille Woringer Award Brain Institute were among the final recipients. The organized in December with more to follow Halphen Award from the Medical Research Institute’s success rate is 34%, which is twice the at the start of 2021. Foundation national average (16.8%), a sign of the quality and soundness of the projects put forward.

th 15 ERC FUNDING FOR THE INSTITUTE Stanley Durrleman (Inria) Maha Dahawi Young Researcher Award L’Oréal - UNESCO for In 2020, Claire Wyart, team leader (Inserm) at Paris — INRIA/Académie des women in science 2020 Brain Institute, was awarded an ERC Consolidator Sciences Young talent award Grant, competitive European funding, for the ” TOGETHER, WE REPRESENT A CRITICAL MASS OF A NEW CAMPAIGN scientific excellence of her ”Exploratome” project. OVER 2,000 RESEARCHERS. WE HAVE OBVIOUS This project aims to decipher the spatial-temporal ON BEQUESTS SYNERGIES AND COMPLEMENTARITIES BETWEEN structure of motor patterns by studying how sensory OUR CENTERS, WHICH SHOULD ALLOW FOR A information can induce change in locomotor states. Through the message of this campaign based on VERY EFFECTIVE AND POWERFUL RESPONSE. the message ”At Paris Brain Institute, it is not only Each year, the European Research Council (ERC) OUR ALLIANCE IS PART OF A SHARED EFFORT TO researchers who advance research”, the Institute encourages the best scientific projects through ACCELERATE THE PACE OF SCIENTIFIC DISCOVERY wished to honor those who decide to transfer their competitive calls for projects open to all researchers in AND PROMOTE BREAKTHROUGHS IN THE FIELD OF estate to the Paris Brain Institute or to designate it as the the European community. The ERC Consolidator Grants NEURODEGENERATIVE DISEASES. ” beneficiary of a life insurance contract. Thanks to them are awarded to researchers with at least seven and and their financial support, Paris Brain Institute can go Mathilde Lapoix Claire Wyart (Inserm) up to twelve years of experience after their doctoral further in its research and accelerate its discoveries, by Pariscience Festival ERC Consolidator Grant degree and an excellent scientific background. carrying out innovative research programs, by acquiring Symbiose Award Prof. Alexis Brice, cutting-edge equipment or by recruiting teams of Executive Director of Paris Brain Institute researchers based on criteria of excellence.

1212 •• PARISPARIS BRAINBRAIN INSTITUTEINSTITUTE •• 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 13 KEY FIGURES

PARIS BRAIN INSTITUTE PARIS BRAIN INSTITUTE IN THE PAST 10 years IN 2020

11 new teams 734 recruited by international 25 people calls for applications Over 6281 RESEARCH 70 TEAM PUBLICATIONS 88 M incubated selected by an International € since 2012, including 1500 Scientific Committee IN GRANTS with an Impact Factor > 7 companies 37 start-ups incubated received since 2012 and 1,318 in the top 10% in 3 locations 7 of citations MEDICAL (265 in the top 1%) DEVICES 5 fields of research : designed - Molecular & cellular neurobiology at the - Integrative neurophysiology Living Lab 15 - Cognitive neuroscience 10 ERC GRANTS 400 M€ - Clinical & translational neuroscience CUTTING-EDGE (European Brain Council) IN - Computational neuroscience TECHNICAL FUNDRAISING PLATFORMS

Over including BioBanks 900 (>55,000 patients, 13 10,000 tumors, 330 brains) JOBS CREATED clinical research 173 infrastructures clinical trials 8 1 CARE LAB innovative and products 1 FABLAB launched 600 publications in international scientific journals

12 training programs at the Open Brain School with over 1,500 participants 244,283 donors

14 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 15 Research

THE MENINGEAL LYMPHATIC NETWORK, A NEW POSSIBILITY FOR TREATMENT OF BRAIN A YEAR TUMORS Does the recently characterized meningeal lymphatic network play a role in the brain’s FILLED WITH immune protection? Does this network faci- litate the entry of antigen-specific immune SCIENTIFIC cells into brain tissue? The research carried out by Éric Song from Akiko Iwasaki’s team (Yale, United States) and Jean-Léon Tho- BREAKTHROUGHS mas (Inserm/Yale) at Paris Brain Institute highlighted a beneficial role for the menin- geal lymphatic vascular network in the short and longer-term treatment of glioblastoma multiforme (GBM). Strengthening the me- ningeal lymphatic vessel network increases the traffic of tumor antigen-presenting cells from the meninges to the lymph nodes. The authors conclude that the major role of the meningeal lymphatic network would be to transport the immune alert message, trigge- ring the activation of lymphocytes directed 2020 SAW THE CULMINATION against the tumor, from the meninges. OF MAJOR BREAKTHROUGH - Song E, et al. Nature, January 2020. PROJECTS LED BY RESEARCHERS AT PARIS BRAIN INSTITUTE WITH MAJOR SCIENTIFIC TOURETTE’S SYNDROME : MOTOR IMPULSES DO NOT PROGRESS. MAJOR PUBLICATIONS PREDICT PATIENT TICS SPANNED ALL FIELDS OF

RESEARCH COVERED BY OUR Tourette’s syndrome is a highly heterogeneous TEAMS, FROM MOLECULAR AND neuropsychiatric and neurodevelopmental pathology characterized by tics, which CELLULAR NEUROBIOLOGY TO are sudden and repeated involuntary COMPUTATIONAL NEUROSCIENCE, movements. Cyril Atkinson-Clément and Yulia Worbe (Sorbonne University/AP-HP) NEUROPHYSIOLOGY, CLINICAL found that control of motor impulsivity, WORK AND COGNITION. PROOF which characterizes the ability to inhibit THAT DESPITE THE DIFFICULT a movement or an action that has already been initiated, is not correlated with tics CONTEXT, PARIS BRAIN INSTITUTE in patients with Tourette’s syndrome. This TEAMS REMAIN INVOLVED TO discovery sheds light on this pathology, BRING THEIR PROJECTS TO where the search for predictive markers for the progression of the disease is a major FRUITION. issue in order to better manage patient care.

- Atkinson-Clément C, et al. Cortex, 2020.

2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 17 Research

THE FIRST COMPLETE MAPPING OF FUNDAMENTAL PROPERTIES OF ACTIVATION OF THE INNATE CEREBRAL VASCULARIZATION VALUE SYSTEMS WITHIN THE BRAIN IMMUNE SYSTEM WITHIN THE CENTRAL NERVOUS SYSTEM : Nicolas Renier’s team (Inserm) succeeded in Which cognitive mechanisms help us make decisions? reconstructing the entire cerebral vascular system Why do we prefer some options over others? How A BIOMARKER FOR DISEASE of mice with unprecedented precision. While many is the value of an option estimated by the brain? PROGRESSION IN MULTIPLE neurological and psychiatric pathologies have a A study conducted by Alizée Lopez-Persem in SCLEROSIS ? vascular component, the complexity of the network of Mathias Pessiglione’s team (Inserm) highlighted the blood vessels, intimately intertwined with neural cells, main characteristics of the neural signal involved in A study conducted by Benedetta Bodini (AP- complicates research. The instrument developed by the value judgments. This study identified four essential HP / Sorbonne University) and Émilie Poirion, in research team paves the way for important findings on properties of the neural signal observed in the the team led by Bruno Stankoff and Catherine the role of cerebral vascularization in the development orbitofrontal cortex (area of the brain located in the Lubetzki (AP-HP/Sorbonne University), has of many brain diseases. prefrontal cortex, just behind the eye sockets). These enabled the development of a new method to four properties explain attribution errors in value - Kirst C, et al. Cell, February 2020. map activation of microglia in the white matter judgments. We sometimes believe we are estimating of the central nervous system that contains the value of one option, while we are in fact influenced the majority of neuron axons. The researchers by the value of another. succeeded in reconstructing individualized

- Lopez-Persem A, et al. Nature Neuroscience, April activation profiles of innate immune cells, and 2020. pinpointed white matter lesions presenting a persistent activation of the microglia in patients when they were considered as perfectly stable GENETICS AND MECHANISMS and inactive in standard MRIs. Activation of microglia in lesions is a promising biomarker INVOLVED IN DRUG RESISTANCE for the evolution of patient disability, which will IN BRAIN TUMORS need to be confirmed by future prospective studies. This will hopefully lead to more Mehdi Touat and Franck Bielle (AP-HP/Sorbonne efficiently adapting the treatment of patients University), from the team led by Marc Sanson with multiple sclerosis, assessing new therapies, and Emmanuelle Huillard and from the neuro- and preventing the progression of disability as oncology and neuropathology departments of the much as possible. Pitié-Salpêtrière AP-HP Hospital, in collaboration - Bodini B, et al. J Nucl Med, 2020. with Yvonne Li, Rameen Beroukhim, Pratiti Bandopadhayay and Keith Ligon of the Dana Farber Cancer Institute (Harvard Medical School, Boston), highlighted genetic changes in certain recurrent MYELIN DEFICIT LEADS ONSET OF BEHAVIORAL gliomas that lead to resistance to chemotherapy. The TO COGNITIVE DISORDERS study, beyond its very comprehensive approach in INDIVIDUALITY IN THE BRAINS IN A SCHIZOPHRENIA MODEL molecular and mechanistic analysis, deals with the OF FLIES : A GENERAL PRINCIPLE largest sample ever to be explored in brain tumors. Using an experimental model of schizophrenia, FOR NEURODEVELOPMENTAL ORIGIN The results obtained will make it possible to provide Dorien Maas and Brahim Nait-Oumesmar OF PERSONALITY ? information on the response to chemotherapy during (Inserm) in collaboration with Gerald Martens the diagnosis of tumors and during treatment, (Donders Institute, Nijmegen, Netherlands) in particular in the event of recurrence after Where does our individuality come from? What demonstrated that spatial memory and social chemotherapy, where the use of high-throughput makes us unique in our behavior? Could the answer lie behavior disorders depend on the prefrontal DNA sequencing techniques would make it possible in our brain? Bassem Hassan and his team discovered cortex. These cognitive disorders have been to tailor treatments to patient’s needs. a random neural circuit formation mechanism in the associated with hypomyelination of parvalbumin brain of the Drosophila melanogaster fly that causes - Touat M, et al. Nature, April 2020. interneurons in the prefrontal cortex, following a individual behavior. These findings may represent halt in oligodendrocyte maturation. In addition, a general principle of how certain aspects of researchers have shown that environmental individuality emerge in the brain. enrichment (physical activity, social interactions, etc.) corrects developmental alterations in - Linneweber GA, et al. Science, March 2020. myelination of the prefrontal cortex. These results pave the way for new behavioral and/ or pharmacological treatment perspectives to promote myelination in schizophrenia.

- Maas DA, et al. Nature Communications, 2020. 18 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 19 A NEW CLINICAL SIGN most frequent cause of recessive genetic forms of POUR SONDER L’ÉTAT DE CONSCIENCE early-onset Parkinson’s disease before the age of 40. Their recent findings also provide valuable informa- tion to guide genetic testing and counseling in newly Lionel Naccache (AP-HP/Sorbonne University) and diagnosed patients and their families. They will also his team have identified and validated a new clinical make it possible to stratify patients into cohorts for examination sign that highlights enhanced brain future clinical trials targeting deficits associated with function in non-communicating patients. They observed PRKN and PINK1 mutations, and more generally to that the startle reflex response to noise (eyelid blinking monitor symptom progression. after a sudden sound) exhibited habituation in patients who were able to predict and anticipate this repetition. - Lesage S, et al. Annals of Neurology, May 2020. Beyond this precious diagnostic information, the presence of this clinical sign that is easy to spot at the patient’s bedside also made it possible to predict HUNTINGTON’S DISEASE : an improvement in their state of consciousness six CEREBRAL ANOMALIES months later. The invention of new clinical signs based on the latest structural and functional brain imaging COULD BE DETECTED IN EMBRYOS techniques also demonstrates the contemporary vitality and constant renewal of neurological semiology. Huntington’s disease is a genetic neurological disease with typical onset in adulthood. Sandrine Humbert - Hermann B, et al. Brain, June 2020. (Inserm) at the Grenoble Institute of Neuroscience and Alexandra Durr (AP-HP/Sorbonne University) at Paris Brain Institute discovered abnormalities in the brains IMPROVING CONSCIOUSNESS WITH of human embryos carrying the mutation responsible ELECTRICAL STIMULATION OF for Huntington’s disease. This research sheds light on THE BRAIN CORTEX mechanisms of silent disease progression, and when and how to treat patients in the future. TO PERSEVERE OR TO EXPLORE : A study by Lionel Naccache’s team (AP-HP/Sorbonne - Barnat M, et al. Science, July 2020. University) reveals how transcranial direct current NEURAL BASES OF THE electrical stimulation (tDCS) of the frontal lobe of EXPLOITATION - EXPLORATION patients with disorder of consciousness improves their CHARACTERIZING DILEMMA state of consciousness. These results are important NEURODEGENERATION OF both from a clinical standpoint - by paving the way Psychiatrist and researcher Philippe Domenech (Henri for the development of new treatment strategies for SUBSTANTIA NIGRA THROUGH SPACE Mondor AP-HP Hospital), in the “Neurophysiology of tailored stimulation - and from a fundamental research AND TIME IN PARKINSON’S DISEASE repetitive behaviors” team at Paris Brain Institute, standpoint by confirming the importance of the along with Sylvain Rheims from the neurology and prefrontal cortex and the fronto-parietal network in the Emma Biondetti, a member of the team led by Marie epileptology department of the Hospices Civils de physiology of consciousness. These findings are in line Vidailhet and Stéphane Lehéricy (AP-HP/Sorbonne Lyon Hospital and Étienne Koechlin of École Normale with the global neuronal space theory developed over University), found that there is a progressive Supérieure - PSL revealed the brain mechanisms the past twenty years by Stanislas Dehaene, Jean-Pierre decrease in neuromelanin in Parkinson’s Disease, behind the decision to explore one’s environment Changeux and Lionel Naccache. visible on MRI, as well as an overall reduction in in order to establish new strategies. This is the first substantia nigra volume. Changes in neuromelanin electrophysiology study to identify brain mechanisms - Hermann B, et al. Scientific reports, June 2020. begin in the posterior regions of the substantia underlying the resolution of the exploitation- nigra, more specifically involved in motor function. exploration dilemma in humans. The identification of a The results also highlight that the various symptoms predictive encoding process, the importance of which LARGE-SCALE EXPLORATION (motor, cognitive and behavioral) associated with was already known for perception, demonstrates OF GENETIC FORMS OF black matter involvement are observed in distinct that it is also essential to executive functions such as PARKINSON’S DISEASE regions of this structure. The substantia nigra region decision making, suggesting that it may be a general therefore associated with the development of motor mechanism implemented throughout the cerebral In 1990, a large cohort on Parkinson’s disease was set symptoms is different from that associated with cortex. up by Professor Alexis Brice as part of a national and cognitive or behavioral symptoms. This data confirms - Domenech P, et al. Science, August 2020. international network coordinated by Paris Brain Ins- the value of neuromelanin as a biomarker for the titute at Pitié-Salpêtrière Hos-pital. The patients in- progression of Parkinson’s disease and its symptoms. cluded participate in genetic analysis as well as a cli- It provides new research directions in the evaluation nical evaluation. With-in this cohort and in over 1,600 of the effectiveness of treatments on the progression individuals, Suzanne Lesage (Inserm) and her collabo- of the disease in future clinical trials. rators searched for abnormalities in three genes, PRKN - Biondetti E, et al. Brain, 2020. (Parkin), PINK1 and DJ-1, the mutations of which are the

2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 21 PROMISING RESEARCH ON THERAPY CLINICAL VALIDATION OF AN MULTIPLE SCLEROSIS : IN AMYOTROPHIC LATERAL AUTOMATIC LEARNING ALGORITHM CELLS IN CHARGE OF MYELIN REPAIR SCLEROSIS (ALS) FOR DIAGNOSIS OF PARKINSONIAN DISPLAY NO INTRINSIC ANOMALIES SYNDROMES ALS is characterized by degeneration of motor As part of an international consortium, Anne Baron-Van neurons, that are directly connected to a muscle Researchers and clinicians from Paris Brain Institute Evercooren (Inserm) and Tanja Kuhlmann (Münster, and control its contractions. The spinal motor at Pitié-Salpêtrière AP-HP Hospital have validated Germany) found that the lack of remyelination in some neurons affected in ALS have the specificity of being the clinical use of a machine learning algorithm using patients with relapsing-remitting multiple sclerosis is surrounded both by microglial cells in the spinal magnetic resonance imaging (MRI) data. This algorithm not linked to an intrinsic defect in oligodendrocytes, cord and by peripheral macrophages in the nerve, differentiates subjects suffering from parkinsonian myelinating cells of the brain, but in the toxic and the part of the motor neuron that exits the spine to syndromes such as Parkinson’s disease, progressive inflammatory environment of the lesions. connect the muscle to the periphery. Séverine Boillée’s supranuclear palsy or multisystem atrophy. In the - Starost L, et al. Acta Neuropathologica, September 2020. team (Inserm) has found for the very first time that future, the addition of new biomarkers, such as the - Mozafari S, et al. Science Advances, September 2020. peripheral macrophages play an important role in the measurement of iron deposits in tissues, could increase development of amyotrophic lateral sclerosis (ALS), diagnostic precision. The integration of this type of paving the way for new therapeutic approaches for algorithm into the clinical man-agement of Parkinson’s patients. In the longer term, development of research disease may improve future diagnosis of parkinsonian aimed at treating neurotoxic macrophages outside the syndromes at an early stage. central nervous system, in a less invasive way, could lead to a significant decrease in the death of motor - Chougar L, et al. Movement Disorders, November neurons in patients with ALS. These results pave the 2020. way for promising research opportunities on treatment.

- Chiot A, et al. Nature Neuroscience, September 2020. A NEW CEREBRAL CHANNELOPATHY THAT ASSOCIATES INTELLECTUAL MAKING SENSE OF THE WORLD : DISABILITY AND ABNORMAL THE NEURAL BASIS OF ABSTRACTION MOVEMENTS

We are constantly confronted with immense amounts Dysfunctions of ion channels – or channelopathies of information from our environment: what we see, – in the brain are currently associated with over 30 hear, smell, the objects we interact with and the situa- neurological diseases such as epilepsy or cerebellar tions we experience. In order to navigate this, our brain ataxia. A study conducted by Fanny Mochel (AP- integrates all of these explicit factors, simplifies and ag- HP/Sorbonne Université) and Christel Depienne gregates them to create implicit rules. A study conduc- identified a new cerebral channelopathy originating ted at the Zuckerman Institute at Columbia University from dominant mutations in the KCNN2 gene, (United States) by Jérôme Munuera, co-first author and encoding the SK2 ion channel. This new pathology NEW FINDINGS ON A MAJOR researcher at Paris Brain Institute, and his collaborators, includes strongly heterogeneous symptomatology NEW DATA CONFIRMS BENEFITS PROTEIN INVOLVED IN ALZHEIMER’S highlights a «geometry of abstraction». During the neural and requires multidisciplinary care with genetics, OF DEEP BRAIN STIMULATION response, the number of dimensions is reduced to the to look for KCNN2 mutations, neuropediatrics, and DISEASE TO TREAT OBSESSIVE-COMPULSIVE most essential, leaving only major contextual elements to neurology to manage cognitive and motor symptoms in patients. A study conducted by Irini Kessissoglou, in Bassem DISORDER generate optimal behavior without saturating the brain with unnecessary information. This discovery opens new Hassan’s team (Inserm), reveals new functions for the - Mochel F, et al. Brain, 2020. perspectives in certain neuropsychiatric deficits and in equivalent of the amyloid precursor protein (APP) A study by researchers and clinicians from Paris Brain the field of artificial intelligence. By better understanding in Drosophila flies in a physiological context and Institute and AP-HP (Henri Mondor and Pitié-Salpêtrière the integration of different dimensions in the brain and underlines its importance for homeostasis of the adult Hospitals) confirmed the beneficial effect of deep brain neural networks, it may be possible to apply this integra- brain. Findings regarding the consequences of loss of stimulation on several brain structures in severe drug-re- tion to algorithms and to develop new and more efficient APP suggest a strong link between its physiological sistant obsessive-compulsive disorders, highlighting machine learning techniques. functions and the deficiencies observed in familial the importance of precise identification of underlying Alzheimer’s disease. The initial effects observed neural networks. Research is still needed to identify pre- - Bernardi S, et al. Cell, October 2020. in flies lacking APP support the idea of long-term cise characteristics predicting patient response to deep changes in the brain occurring before the onset of brain stimulation. clinical symptoms, suggesting new research into early - Welter ML, et al. Biological Psychiatry, October 2020. endosomes and neuron and glial cell interactions in this disease.

- Kessissoglou IA, et al. PLoS Biology, December 2020.

22 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 23 Research

DISCOVERY OF A PLASMA SIGNATURE OF FRONTO- NEUROCOVID -19 TEMPORAL DEGENERATION CALL FOR PROJECTS AND AMYOTROPHIC LATERAL Very shortly after the onset of the pandemic, SCLEROSIS LINKED TO C9ORF72 neurologists suspected that the nervous GENE MUTATION system may be affected, directly or indirectly, A joint study by the teams led by Olivier Colliot during a COVID-19 infection. In June, Paris Brain (CNRS) and Isabelle Leber (AP-HP) at Paris Brain Institute and Inria (Rennes and Paris centers) Institute launched an internal call for projects revealed, for the very first time, microRNA plasma in collaboration with Institut Pasteur (IP) to signatures in individuals with symptomatic or finance new proofs of concept (new models, pre-symptomatic frontotemporal degeneration and amyotrophic lateral sclerosis. The discovery development of instruments and technology of this potential new biomarker represents for analysis, etc.) on how infection impacts a an important advance in assessing clinical progression of patients and efficacy of future healthy or pathological nervous system. This treatment candidates in therapeutic trials. call for projects was launched thanks to the

- Kmetzsch V. et al. Journal of Neurology, support of its patrons and donors, including Neurosurgery and Psychiatry, 2020. the OCIRP Foundation and Accuracy.

EARLY COGNITIVE DISORDERS IN SUBJECTS AT RISK OF DEVELOPING FTD/ALS

Patients with frontotemporal degeneration show impairment in cognitive and behavioral inhibition, PROJECTS which allows us not to respond to all the stimuli we are confronted with on a daily basis and to WERE SELECTED : suppress behaviors unsuited to the different situations we face. A study that stemmed from a collaboration between the teams of Isabelle Le > COV-2 BRAIN : Pathophysiology of central ner- Ber (AP-HP) and Lara Migliaccio (Inserm) at Paris vous system infection by the SARS-CoV-2 coronavirus, Brain Institute found that assessing cognitive by Nicolas Renier (Inserm) and Stéphane Haïk (Inserm) inhibition is a highly important marker in the early detection of abnormalities in individuals at risk of > COV-2-NEURO-SENSING : Study of the interac- developing a neurodegenerative pathology. This tion between SARS-CoV-2 and sensory neurons of the assessment of cognitive inhibition may prove central nervous system, by Claire Wyart (Inserm) and to be essential to stratify patients and identify Jean-Pierre Levraud (IP) asymptomatic carriers of the mutation in order to set up treatment trials. > BRAIN-COV : Characterization of brain lesions due to infection by SARS-CoV-2, by Mathieu Santin - Montembeault M, et al. Journal of Neurology, (Paris Brain Institute), Danièle Seilhean (AP-HP/Sor- Neurosurgery and Psychiatry, 2020. bonne University), and Roberto Toro (IP)

> COVESSEL : Identification of the infection pathways of the SARS-CoV-2 coronavirus in the cen- tral nervous system, by Nicolas Renier (Inserm) and Pierre-Marie Lledo (IP)

24 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT Research ACQUISITION EVOLUTIONS IN RESEARCH OF A NEW CUSTOM-MADE AND DEVELOPMENT PROGRAMS MULTIPHOTON MICROSCOPE CUTTING-EDGE FabLab, also known as a ”workshop”, is set to evolve Paris Brain Institute acquired a new multiphoton towards becoming an R&D platform with a wider TECHNOLOGICAL microscope with the generous support of the Edmond array of services offered. This new R&D unit will J. Safra foundation. It is custom-made and will allow combine design, production and personalization for various Institute teams to develop in-depth and the entire Paris Brain Institute ecosystem. PLATFORMS multiscale research. Multiphoton microscopy allows scientists to acquire imaging of the depths of animals’ brains during development or while undertaking a behavioral task. This type of instrument is essential to establish relationships between brain activity and behavior.

” DEVELOPMENTAL AND BEHAVIORAL IMAGING

INVOLVES LENGTHY EXPERIMENTS WHERE AN

INSTRUMENT CAN REMAIN IN USE FOR HOURS AT A IN 2020, THE INSTITUTE TIME, AND SOMETIMES UP TO 24 HOURS IN A ROW. THIS ACQUISITION, MADE POSSIBLE WITH SUPPORT COMMITTED TO INCREASING FROM THE EDMOND J. SAFRA FOUNDATION, WILL HELP

PLATFORM INTERDISCIPLINARITY, BOOST OUR RESEARCH, AND ESPECIALLY OUR PROJECT

AND OFFER RESEARCH TEAMS DEDICATED TO UNDERSTANDING THE NEURAL BASIS OF A WIDER ARRAY OF SERVICES. INDIVIDUALITY. ” DESPITE THE HEALTH CRISIS, INSTITUTE PLATFORMS MAINTAINED HIGH-LEVEL SERVICE Prof. Bassem Hassan, team leader THAT ALLOWED SCIENTIFIC and scientific director at Paris Brain Institute PROJECTS TO PROGRESS AND NOVASEQ SEQUENCER ATTAIN COMPLETION. ON IGENSEQ PLATFORM GETS AN UPGRADE STRATEGIC CHANGES ARE IN PROGRESS TO OPTIMIZE In 2019, the Paris Brain Institute acquired the Novaseq 6000 ILLUMINA, the world’s most powerful PLATFORM ACTIVITY AT THE short fragment DNA sequencer, for the iGenSeq EVOLUTION INSTITUTE. THEY WILL ALLOW core facility. OF THE BIOINFORMATICS FOR BETTER INTEGRATION WITHIN Sequencing capacity was increased as well as PLATFORM single-cell sequencing capabilities THE SCIENTIFIC ECOSYSTEM AND THE INSTITUTE’S STRATEGY, WILL Lars Jorgensen joined the bioinformatics TOWARDS HELP PRIORITIZE SCIENTIFIC AND platform in 2020 in the role of operational manager. He brings extensive internatio- NEW CUTTING-EDGE EQUIPMENT TECHNICAL GOALS, AND MAINTAIN nal experience to his new position and is A LEVEL OF EXCELLENCE FOR THE currently working with his team on a full Paris Brain Institute values access to cutting-edge redesign of platform activities and greater equipment for its researchers. A current institute INSTITUTE’S PLATFORMS. integration with other departments and priority is the acquisition of a 7T MRI. Various platforms. calls for tender and fundraising options are under consideration.

26 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 27 Research

IGENSEQ IVECTOR CELIS TECHNOLOGICAL Next generation RNA Development of molecular Screening, and DNA sequencing instruments for genetransfer cell culture, IPSC, (lentivirus, adenovirus, electrophysiology PLATFORMS CRISPR) AND BIOBANKS

HISTOMICS PHENOPARK DAC Histomics research Preclinical functional Genomics, using specific equipment exploration, behavioral bioinformatics to cut tissue and process analysis, surgery, and biostatistics samples electrophysiology

The progress and quality of science de- pend as much on technological progress ICMQUANT CENIR PRISME as on good ideas. At Paris Brain Institute, researchers and core facilities managers conventional fluorescence Center for Cognitive and social work together to keep abreast of tech- microscopy, confocal laser Neuroimaging Research : assessment in real-life nological advances in order to provide scanning microscopy, 3T MRI, PET-MRI, TMS, conditions and virtual reality the most advanced equipment and tech- bi-photonic microscopy, MEG-EEG, Gait analysis, niques, operated by highly competent staff, to advance brain research. confocal rotating Stereotactic imaging disk microscopy and The Institute’s researchers work at diffe- transmission electron rent scales: from the molecule (DNA, microscopy proteins, etc.) to the individual, as well as the cell. For each of these scales, innova- tive technologies are made available to researchers, clinicians and start-ups. This network of core facilities at the Paris Brain BIOBANKS Institute facilitates translational and trans- disciplinary research. Biological resource collection, DNA, plasma, cells, brain tissue

2828 •• PARISPARIS BRAINBRAIN INSTITUTEINSTITUTE •• 20202020 ANNUALANNUAL REPORTREPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 29 Research

2020 was a very important year for the Institute with IHU a high number of publications in the best journals : 3 Science, 1 Nature, 2 Nature. Neuroscience, 1 Cell. In 2020, Paris Brain Institute now hosts its 15th ERC PARIS (funding from the European Research Council). The year 2020 was also the year of the COVID-19 pande- mic. Measures implemented by Paris Brain Institute INSTITUTE OF management have been effective in guaranteeing staff safety, participating in national collective ef- TRANSLATIONAL forts and maintaining research momentum. A total of 173 clinical trials are underway, a testa- NEUROSCIENCE ment to our high level of clinical research. The Neu- rotrials framework created to assess drugs in early development achieved major results in 2020 with 3 ongoing studies in collaboration with the pharma- ceutical industry. BASED ON THE PLAN The Institute signed 42 new industrial contracts PRESENTED TO THE IHU SINCE 2012, INITIATIVES with biotechnology, pharmacy and medical techno- logy companies for both preclinical research pro- JURY AND IN LINE WITH OUR FUNDED BY THE HOSPITAL- grams and clinical programs. In 2020, the incuba- ROADMAP, WE PURSUED UNIVERSITY INSTITUTE (IHU) tor operated the second acceleration program for the ”Pfizer Innovation France” endowment fund OUR AMBITIOUS GOALS IN DEVELOPED AS PART OF THE and launched its first acceleration program with SCIENCE, MEDICAL RESEARCH, ”INVESTMENTS IN THE FUTURE” Janssen. Around ten digital health startups have be- EDUCATION AND INNOVATION PROGRAM, HAVE HAD MAJOR nefited from the support of the incubator and the Care Lab, as well as the expertise of a leader in the BY CONTINUOUSLY WORKING SCIENTIFIC, CLINICAL AND pharmaceutical industry. TO INCREASE OUR ECONOMIC ECONOMIC IMPACT. This past year also saw investments in digital tech- IMPACT DESPITE THE PANDEMIC. nology and the integration of Education Techno- IN 2019, PARIS BRAIN logy approaches in the Open Brain School curri- INSTITUTE SAW ITS IHU culum. Our concern was to maintain access to our events and training programs while taking into ac- PROGRAM RENEWED WITH count the effects of distance learning on partici- AN ADDITIONAL 17 MILLION pants. EUROS, DEMONSTRATING THE EFFICIENCY OF THE ”IHU MODEL”.

15 173 42 ERCs clinical trials new industrial contracts

30 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 31 Research SUPPORTING RESEARCH PARIS BRAIN INSTITUTE AND ITS NEED FOR FUNDING Research institutes have developed a dynamic financial strategy to cope with the ever-changing regulations of public financial support TEAMS and to adapt to the industrial environment, where new trends and new needs arise almost daily. The Department of Medical and Scienti- fic Affairs (DAMS) is home to a grants office that offers numerous ser- vices to the Paris Brain Institute community and is available to assist in developing new external collaborations. With a wide range of skills, DAMS offers sourcing and engineering assistance to obtain compe- titive research grants on a national, European and international level. ALS : CAUSES AND MECHANISMS OF CELLULAR PHYSIOLOGY OF MYELINE PLASTICITY ARAMIS : MOTOR NEURON DEGENERATION CORTICAL MICROCIRCUITS AND REGENERATION ALGORITHMS, MODELS AND Séverine Boillée (Inserm) Compe- Alberto Bacci (Inserm) Competitive Brahim Nait-Oumesmar (Inserm) and METHODS FOR IMAGES AND SIGNALS titive grants received in 2020 : ANR- grants received in 2020 : ANR-PRC, Violetta Zujovic (Inserm) Competitive OF THE HUMAN BRAIN PRCE, ARSLA, FRM FRM, Fondation Jérôme Lejeune grants received in 2020 : ARSEP Olivier Colliot (CNRS) and Stanley Durrleman (Inria) 16,7 M€ BASIC TO TRANSLATIONAL CELLULAR EXCITABILITY AND PICNIC- PHYSIOLOGICAL Competitive grants received in 2020 : of external NEUROGENETICS NEURAL NETWORK DYNAMICS INVESTIGATION OF CLINICALLY ANR-PRC, Plan cancer, Inserm, competitive grant Académie des Sciences Giovanni Stevanin (Inserm/EPHE) and Stéphane Charpier (Sorbonne Uni- NORMAL AND IMPAIRED COGNITION income 2020 Alexandra Durr (Sorbonne Université/ versité), Mario Chavez (CNRS) and – NEUROPSYCHOLOGY AND 1 AP-HP) Competitive grants received Vincent Navarro (Sorbonne Univer- FUNCTIONAL NEUROIMAGING EXPERIMENTAL NEUROSURGERY ERC in 2020 : FRM, NIH, Association CSC sité/AP-HP) Competitive grants re- Laurent Cohen (Sorbonne Université/ Brian Lau (CNRS) and Carine Karachi consolidator (Sorbonne Université/AP-HP) ceived in 2020 : FRM, Fondation Ge- AP-HP), Lionel Naccache (Sorbonne grant in 2020 MOLECULAR PATHOPHYSIOLOGY nerali, FFRE Université/AP-HP) and Paolo Barto- Competitive grants received in 2020 : i.e. 15 since the creation 3 OF PARKINSON’S DISEASE lomeo (Inserm) Competitive grants MSCA/IF-GF, ANR-CoEN, ANR- PRC, ANR-CRCNS, Fondation pour of the Institute MSCA fellowships Olga Corti (Inserm) and Jean-Chris- GENETICS AND PHYSIOPATHOLOGY received in 2020 : MSCA-IF/GF, ANR- in 2020 PRC, Fondation pour la recherche la Recherche sur Alzheimer, France tophe Corvol (Sorbonne Université/ OF EPILEPSY i.e. 22 since the creation AP-HP) Competitive grants received in sur les AVC, Foundation for Polish Parkinson Éric Leguern (Sorbonne Université / of the Institute 2020 : ANR-PRC, FRM, MJFOX, ANR– AP-HP) and Stéphanie Baulac (In- Science, FRM, HAS-Haute Autorité de BRAIN DEVELOPMENT ERAPerMed, Fondation de France serm) Competitive grants received Santé Bassem Hassan (Inserm) in 2020 : FRM, Prix L’Oréal UNESCO, Competitive grants received in 2020 : ALZHEIMER’S DISEASE LFCE FRONTLAB : FRONTAL FUNCTIONS FRM, Fonds de dotation Neuroglia, AND PRION DISEASES AND PATHOLOGY ANSES Marie-Claude Potier (CNRS) and SENSORY SPINAL SIGNALING Richard Lévy (Sorbonne Université/ ACRONYMS Stéphane Haïk (Inserm) Competitive AP-HP) Competitive grants received Claire Wyart (Inserm) Competitive STRUCTURAL DYNAMICS OF NEURAL grants received in 2020 : ANR-PRC, grants received in 2020 : FRM, Fon- in 2020 : MSCA/IF-GF, ANR-PRC, NETWORKS • ANR-CoEN : National • ANSES : National Food • FRM : Foundation for ANR-ERAPerMed, LRTCA, Fondation FRC, ANR-LABCOM, FRM dation des Treilles, ERC-Consolidator Nicolas Renier (Inserm) Research Agency – and Hygiene Safety Medical Research pour la Recherche sur Alzheimer Expert Centers for Agency Competitive grants received in 2020 : • H2020 : Horizon 2020 CIA : COGNITIVE CONTROL — Neurodegenerative GENETICS AND DEVELOPMENT OF MSCA-ITN/ETN, FRM Diseases • APHP : Assistance European Program EXPERIMENTAL THERAPEUTICS INTEROCEPTION – ATTENTION Publique — Hôpitaux NERVOUS SYSTEM TUMORS • IMI : Innovative OF PARKINSON’S DISEASE Philippe Fossati (Sorbonne Université/ • ANR-CRCNS : National de Paris (Paris Hospital Emmanuelle Huillard (CNRS) and Marc CELLULAR MECHANISMS OF Research Agency — System) Medicine Initiative Étienne Hirsch (CNRS) and Stéphane AP-HP) and Liane Schmidt (Inserm) Sanson (Sorbonne Université/AP-HP) SENSORY PROCESSING Collaborative Research • LFCE : French Epilepsy Hunot (CNRS) Competitive grants re- Competitive grants received in 2020 : in Computational • ARDRM : Robert Debré Competitive grants received in 2020 : Nelson Rebola (CNRS) Association for Medical League ceived in 2020 : ANR-CoEN, Fonda- ANR-PRC Neuroscience INCA, DoD – Department of Defense, Competitive grants received in 2020 : Research • LRTCA : Advanced tion de France • ANR-ERAPerMed FRM, Ligue contre le cancer, APHP, MSCA/IF-GF, ANR-PRC • Association CSC : Surgical Technology NEUROPHYSIOLOGY OF : National Research Research Laboratory ARTC, ANSES, Cancéropôle Île-de- Agency — Translational Understanding Cerebellar Syndromes MOV’IT : MOVEMENT, France, FRM, GEFLUC Paris REPETITIVE BEHAVIORS GENE THERAPY Medicine Project • MSCA-IF/GF : Marie INVESTIGATION, THERAPEUTICS. Éric Burguière (CNRS) Competitive • ARSEP : Association Skłodowska-Curie Nathalie Cartier (Inserm) • ANR-JCJC : National actions — Individual NORMAL AND ABNORMAL MOTOR grants received in 2020 : Fondation for Research on Multiple REMYELINATION IN MULTIPLE Competitive grants received in 2020 : Research Agency — and Global Fellowships Young Researcher Sclerosis CONTROL : MOVEMENT DISORDERS SCLEROSIS : FROM BIOLOGY TO FondaMental, ANR-PRC IMI, ANR-JCJ, ARSLA, Inserm, Asso- (Europe) AND EXPERIMENTAL THERAPEUTICS • ARSLA : Association CLINICAL TRANSLATION ciation française du Syndrome de Rett • ANR – JPND : National • MSCA-ITN/ETN : Research Agency for Research on Marie Vidailhet (Sorbonne Université / Catherine Lubetzki (Sorbonne Univer- MOTIVATION, BRAIN AND BEHAVIOR Marie Skłodowska-Curie — Joint program on Amyotrophic Lateral AP-HP) and Stéphane Lehéricy (Sor- Mathias Pessiglione (Inserm), Sébas- Sclerosis actions — Innovative sité/AP-HP) and Bruno Stankoff (Sor- DIANE BARRIÈRE CHAIR : neurodegenerative Training Network/ bonne Université/AP-HP) Competitive bonne Université/AP-HP) Competitive tien Bouret (CNRS) and Jean Dau- “MOLECULAR PHYSIOLOGY OF diseases • ERC : European European Training grants received in 2020 : ANR-JCJC, grants received in 2020 : NeurATRIS, nizeau (Inserm) Competitive grants SYNAPTIC BIOENERGETICS” • ANR — PRC : National Research Council Network ANR-JNPD, ANR-PRC, AMADYS, received in 2020 : ANR-PRC, H2020, Research Agency — FRM, ARSEP, Fondation Sorbonne Jaime De Juan-Sanz (CNRS) • FFRE : French Epilepsy • NIH : National Institutes Fondation Generali, ANR-TREMPLIN, Académie des Sciences Collaborative research Research Foundation of Health (United States) Université projects SFRMS, Fondation pour la Recherche sur Alzheimer, PSP France

32 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 33 Research INTERNATIONAL CURE-ND PARTNERSHIPS (France, Germany, United-Kingdom, Belgium) A highlight the year 2020 was the creation of the CURE-ND “Catalyzing a United Response in Europe to Neurodegenerative Diseases” consortium, which brings together Paris Brain Institute and our long-standing partners the UK Dementia Research Institute, the German DZNE and the Belgian Mis- sion Lucidity (VIB). With a critical mass of over 2,000 researchers, this wor- DESPITE THE PANDEMIC, king group aims to develop a new European network of excellence in neuro- degenerative diseases. The launch event was held online in December 2020 THE INSTITUTE WAS ABLE TO with the development of a shared framework. MAINTAIN AND INCREASE ITS INTERNATIONAL COOPERATION EFFORTS THROUGHOUT THE MONTREAL NEUROLOGICAL INSTITUTE YEAR. ALTHOUGH INTERNATIONAL (Canada) TRAVEL WAS IMPOSSIBLE AND Although the multidisciplinary workshop scheduled for June 2020 was postponed for a year due to the health EXCHANGES WERE SUSPENDED WEIZMANN INSTITUTE crisis, collaboration with the MNI grew. An online workshop (MIT, STANFORD, YALE, ST JOHN’S dedicated to organoids and IPSCs applied to nervous system (Israel) In 2020, we decided to strengthen our cooperation with the Weizmann UNIVERSITY IN THE UNITED diseases prompted our researchers to come together and fostered discussions on new joint projects. The renewal of our Institute, initiated by a scientific collaboration centered on the funda- STATES), WE ADAPTED MANY cooperation agreement was agreed upon, and discussions mental bases of states of consciousness and non-consciousness. In or- OF OUR ACTIONS TOWARDS are underway regarding further collaboration in other der to promote meetings and the development of innovative projects, specialties : iPSC-based screens, multimodal data analysis we have planned scientific workshops as well as organization and sup- DIGITAL PLATFORMS. THIS YEAR, and neurodevelopmental disorders. port for research and student exchanges between the two Institutes ONCE AGAIN, THE INSTITUTE on a regular basis. COOPERATED WITH RESEARCHERS FROM DIFFERENT INSTITUTES THROUGH PUBLICATIONS AND BY OBTAINING NATIONAL, EUROPEAN AND INTERNATIONAL FUNDING.

YALE UNIVERSITY (USA) While no clinician exchange took place this year due to the situation, clinical collaboration was nevertheless strengthened by pooling our clinical rounds on the initial topics of epilepsy and abnormal movements. A multidisciplinary workshop in September saw the start of a new research collaboration on epilepsy and was a chance to take stock of the recent colla- boration between our teams on COVID-19, with initial results published in the Fall.

34 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 35 Clinical Research and Care

COVID-NEUROSCIENCE COHORT : This study now goes beyond a national framework, COVID-19 STUDYING THE NEUROLOGICAL AND with collaborations with prestigious research centers including Yale and Liverpool Universities as well as PSYCHIATRIC CONSEQUENCES OF with international groups. Funding from Fondation PANDEMIC : SARS-COV-2 INFECTION de France will allow patient monitoring throughout 2021 with the study of long-term consequences on From the very first weeks of the pandemic, doctors the nervous system. They will be key to increasing THE INSTITUTE’S reported neurological symptoms in patients affec- our knowledge of the infection and its consequences ted by COVID-19 such as loss of smell or taste, but on the central nervous system, to benefit patients also more serious effects such as seizures or strokes. first and foremost. CLINICAL Faced with this challenge, within a few weeks in April 2020, the Cohort Covid Neuroscience project coordi- nated by Prof. Jean-Christophe Corvol (AP-HP/Sor- COVID NEUROSCIENCE FORCES bonne University) and Dr. Cécile Delorme (AP-HP) BIO-COHORT was launched and brought together the entire medi- UNITE cal-university Neuroscience department of Pitié-Sal- In line with the Covid Neuroscience Cohort study, pêtrière AP-HP Hospital and Paris Brain Institute. This a collection of biological data is being set up to was made possible with support by the International follow patients affected by COVID-19 who presented Automobile Federation (FIA), the FIA Foundation post-infection and post-vaccination neurological or and Institute donors. Over 600 subjects have been psychiatric symptoms over time. recruited and the first results of the project have already identified a number of effects of this disease FROM THE FIRST WEEKS OF as well factors impacting the COVID-19 severity. COVISEP : COVID-19 IN PATIENTS WITH THE COVID-19 PANDEMIC, THE Several types of brain abnormalities were identified ENTIRETY OF PARIS BRAIN in patients with COVID-19 using brain imaging. These MULTIPLE SCLEROSIS INSTITUTE’S CLINICAL FORCES WAS findings were published in Radiology and provide im- portant data in patients with this disease, and also The COVISEP registry is based on a cohort of pa- TRANSFERRED TO THE HOSPITAL’S identify several potential brain targets for SARS- tients from all expert centers and neurologists who follow patients with multiple sclerosis (MS) in France. INTENSIVE CARE, INFECTIOUS CoV-2 infection. Other publications in the European Journal of Neurology describe common features of It includes nearly 1,000 patients. DISEASES AND PNEUMOLOGY UNITS encephalopathies, visible by positron emission tomo- A retrospective and observational study, coordinated TO SUPPORT TEAM ONSITE. graphy, following infection with SARS-CoV-2, which by Dr. Céline Louapre (AP-HP/Sorbonne University), may reflect an immune system mechanism. Given was published in the scientific journal JAMA Neuro- that these features may appear several weeks after STAFF FROM THE CLINICAL logy. It focused on 347 patients with multiple sclero- infection or upon discharge from intensive care units, sis and infected with COVID-19 between March 1 and INVESTIGATION CENTER ALSO several hypotheses will be examined in the future May 21, 2020. The results of this study show that risk regarding mechanisms involved, including direct da- PROVIDED THEIR EXPERTISE FOR factors for severe forms of COVID-19 (requiring at mage to the central nervous system by SARS-CoV-2, PATIENT RECRUITMENT IN SEVERAL least one hospitalization) are the EDSS score (scale thrombosis, immune mechanisms, and metabolic di- reflecting neurological disability severity), age and COVID-19 TRIALS : sorders. obesity. In contrast, immunomodulatory or immuno- suppressive treatments are not associated with se- > DISCOVERY vere COVID-19. This study is ongoing, with over 1,000 > COVID-ICU patients included and a Franco-Italian collaboration > CORIMMUNO is underway to compare results obtained in each country’s patient registry.

These trials evaluated several therapeutic strategies against SARS-CoV-2, allowing us to gain a better understanding of risk factors for severity.

36 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 37 Clinical Research and Care THE CLINICAL INVESTIGATION CENTER

AP-HP/PARIS BRAIN INSTITUTE WORKS TOWARDS FAST-TRACKS : ACCELERATING TAILORED TREATMENT CLINICAL RESEARCH Before starting, a clinical trial must receive a green light from a CPP (Committee for the Protection of FOR EACH PATIENT Persons) and authorization from the National Drug Safety Agency (ANSM). Research must be carried out under the direction of a qualified investigator in the research field and be supervised and insured by an institutional (INSERM, AP-HP, etc.) or industrial IMPORTANT RESULTS FOR Remyelination and inflammation promoter.

TRIALS CARRIED OUT AT THE in multiple sclerosis In order to best facilitate this process and allow clini- LAUNCH OF THE FIRST CLINICAL NEUROSCIENCE CLINICAL The ON-STIM trial, aimed at promoting remyelination cal trials to start as quickly as possible under the best TRIAL FOR NEUROTRIALS, EARLY INVESTIGATION CENTER by electrical stimulation after an episode of optic conditions, a «fast-track» has been set up between CLINICAL DEVELOPMENT UNIT neuritis in patients with multiple sclerosis, has Paris Brain Institute and AP-HP. A project manager, a data manager and a scientific committee are avai- launched. Another trial on neuroprotection has also In 2020, the Neurotrials team was structured to Antisense oligonucleotides lable for investigators of the medical-university neu- started. Encouraging results have been obtained on become fully operational in its consulting and roscience department to accelerate the regulatory in Amyotrophic Lateral Sclerosis (ALS) the use of IL-2 immunotherapy in the disease. clinical trial management activities with industrial Currently, many promising therapeutic innovations submission process and completion of studies. sponsors. This year was marked by the submission are based on antisense oligonucleotide technology, Active clinical research to the health authorities and the implementation of a phase IIa clinical protocol in acute optic neuritis, with using fragments of genetic material that will interfere in Parkinson’s disease A NEW STEP FOR PARIS BRAIN with message RNA and thereby mediate the several patients already included by the investigating expression of certain proteins in the central nervous Precision therapeutic trials have launched in patients INSTITUTE’S CLINICAL RESEARCH teams. Neurotrials is supporting other gene therapy system. Encouraging results were obtained in ALS with genetic forms of Parkinson’s disease affecting INFRASTRUCTURE (iCRIN) biotechnology companies in Huntington’s disease in a study testing the effect of anti-SOD antisense GBA and LRRK2 genes. The Precise-PD project, and cerebellar ataxias, as well as a biomarker study oligonucleotides, conducted by Dr. François Salachas coordinated by the NS-Park/FCRIN network and The clinical research infrastructures of Paris Brain in Parkinson’s disease. The unit has also provided (AP-HP) at the Clinical Investigation Center. supported by France Parkinson, aims to collect cli- Institute (iCRIN) develop interactions and expertise- consulting services to medtechs (in pain management nical data from patients monitored in expert centers sharing among the Neuroscience Medical-University and gait disorders) and biotechs in neurodegenerative throughout France, associated with a collection of Two immunotherapy trials in Unit (DMU) at Pitié-Salpêtrière Hospital and Paris diseases such as Alzheimer’s and Parkinson’s. The biological samples. The goal is to understand the Brain Institute research teams. They underwent perfect integration of Neurotrials within the Paris progressive supranuclear palsy (PSP) wide variability in disease progression trajectories assessment for the second time this year : the 3 Brain Institute, in particular in its technological PSP is a neurodegenerative disease caused by the using computational approaches and artificial intel- emerging projects were renewed for 3 more years, and entrepreneurial ecosystem, and its proximitý progressive destruction of neurons in different areas ligence for precision and personalized medicine in and 2 of them received a certification of excellence. with clinicians and expert and reference biologists of the brain. A trial coordinated by Prof. Corvol (AP- this illness. A study conducted with Roche laborato- Currently, 12 iCRINs hold a certification of excellence, constitute a major asset in supporting healthcare HP/Sorbonne University) at the Paris Brain Institute ry has also obtained encouraging results on slowing and one is considered an emerging iCRIN. This industrialists for the early clinical development of CIC was conducted to assess the therapeutic effect the progression of motor symptoms in the disease. A initiative makes it possible to support clinical research their product in neurology and psychiatry. phase 3 trial is due to start soon. projects directly with patients of the Neuroscience of an anti-TAU antibody. TAU protein aggregates ab- More information will be available soon on normally in neurodegenerative diseases such as PSP Medical-University Unit. www.neurotrials.fr or Alzheimer’s disease. The results are unfortunately negative and do not conclude on the effectiveness of these therapies.

38 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 39 Innovation and knowledge transfer THE MEDTECH GENERATOR & ACCELERATOR PROJECT (MGA) KEY The MGA Project, coordinated by Paris Brain Institute, RESEARCH brings together the Institut Imagine, the Institut de la Vi- sion and the Institut Pasteur. Supported by BPI with a bud- FIGURES get of 1.2 million Euros over 2 years, it aims at developing APPLICATIONS innovative programs to accelerate the growth and deve- lopment of startups specializing in healthcare and artificial intelligence in the field of neuroscience, genetic and rare diseases.

The MGA project will structure and enliven the regional community of deep tech researchers and entrepreneurs A NEW SITE FOR ACCELERATED to boost the creation of startups hailing from academic promising PRODUCT DEVELOPMENT research and support the acceleration of their commercial molecules development. To do so, the project creates a clear path undergoing Despite a year that was strongly disrupted by the COVID-19 for entrepreneurs from the first phases of their project, characterization crisis, the Institute was able to initiate the development closely steers its progress and adjusts it to ensure effec- work of its third business incubation site in 2020. Over tiveness. The members of the consortium will carry out 1,500 square meters and halfway between Paris Brain Ins- simultaneous high-leverage targeted actions for the deve- titute and Station F campus, the new “Chevaleret” site will lopment of the most advanced startups, including support be an accelerator dedicated to medical technologies and for clinical validation of their products. artificial intelligence in healthcare. It will allow the develop- ment of healthcare technology that is socially responsible, The ultimate goal is to offer an integrated approach to novel technology financially affordable and can be used in prevention and entrepreneurial support through balance between collec- development programs in maintenance of autonomy. Through supported projects, tive and individual actions, putting researchers and entre- currently underway the Institute will ultimately help offer new diagnostic and preneurs in contact with experts within our ecosystems. imaging tools, therapeutic solutions to patients suffering It should thereby help double the number of startups from neurodegenerative and psychiatric illnesses, as well created within the four member Institutes. as help develop new tools intended to improve quality of life and autonomy of these patients.

The development of the activities at the new Chevaleret 5,6 M€ site is made possible by the triple financial support of in new industrial the City of Paris, the Île-de-France Region and the BPI partnerships through the funding of the MGA project (Medtech Gene- CARNOT rator & Accelerator).

Paris Brain Institute coordinates the national FINDMED initiative dedicated to supporting French SMEs in phar- maceuticals. It brings together the following Institutes: Carnot Calym, Chimie Balard Cirimat, Curie Cancer, I2C, Active portfolio of Institut du Cerveau, Imagine, Pasteur MS, Qualiment, FFE, MINES, TN @ UPSaclay, Voir et Entendre, and was recently joined by Carnot Opale and APHP. Since 2016, this consor- patents tium has quadrupled its results with French small and me- 55 dium-sized companies, a proactive approach hailed by go- vernment assessors as "structured and efficient".

In early 2020, when the Board of Directors of the Carnot Institutes Association was renewed, the Paris Brain Ins- titute representative was elected vice-president of the network, in charge of startups and SMEs. startups currently incubated

2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 41 Innovation and knowledge transfer

NEW TECHNOLOGY INCUBATING CANDIDATE DRUGS DEVELOPEMENT INNOVATIVE COMPANIES

2020 saw the development of a transatlantic colla- The team responsible for technology development iPEPS, Paris Brain Institute’s innovative business incubator : with Jansen EMEA, a pan-European sup- boration on Huntington’s disease and spinocerebellar (medical and/or research) structured 2020 by incubator, is located at the heart of the Institute port program, and with Janssen France, AstraZene- ataxias between an American SME and Prof.Alexan- launching two calls for projects. The first, CARNOT as well as within STATION F, the largest startup ca, AG2R La Mondiale and Geopost, a multi-partner dra Durr (AP-HP/Sorbonne University), a physician TOOLS, is intended for researchers at Paris Brain campus in the world since 2017. 2020 also saw the initiative in response to the COVID-19 crisis. specialized in hereditary neurodegenerative diseases. Institute. It aims at developing new research techno- construction of the new Chevaleret campus which These rare diseases are hereditary and incurable neu- logies by relying on developers, the Institute’s pro- will open its doors in 2021. The combination of Several incubated companies have taken important rological pathologies associated with neural degene- totyping laboratory and the skillsets at CARE LAB, these three sites supports the incubator’s growth steps in their development. Scipio Bioscience raised ration in an area of the brain involved in motor, co- the Paris Brain Institute LivingLab, for user interface and will allow Paris Brain Institute to support 6 million euros in funds to revolutionize single-cell gnitive and behavioral functions. Understanding the development. Among the first projects, a digital tool startups in medicine, medical devices and digital sequencing analysis. Carthera received 2 million eu- biological mechanisms underlying these pathologies for processing and archiving electrophysiological health. ros in grants and 10.5 million euros in equity from is a fundamental issue in the search for treatment. data, a new system for 3D cell cultures, and a tool the European Council to deploy its SonoCLoud de- to measure motor behavior of Drosophila flies. The In 2020, the incubator operated the second edi- vice on a clinical level White Lab Genomics, a young The Institute’s proximity to patients has given rise second call for projects, CARER INITIATIVE, is a sis- tion of the ”Pfizer Innovation France” endowment startup, obtained an additional 300,000€ thanks to to a promising scientific project between a research ter initiative to support the development of tools acceleration program. Five digital healthcare star- the French Tech Seed program, recommended by team specializing in models of neuroinflammation and solutions to facilitate patient care. Among the tups benefitted from the support and resources of Paris Brain Institute. and neurodegeneration and a startup founded by a first projects selected are an application to facilitate the incubator, as well as the expertise of a leader patient with Parkinson’s disease. These interactions decision-making for clinical teams, another to help in the pharmaceutical industry. This year also marks between researchers and patients allowed better private practices in the follow-up of patients after a the start of two new industrial partnerships for the scientifical understanding of clinical observations hospital stay, and an instrument to detect sense of and helped consolidate a patent filing for possible smell disorders. therapeutic applications. In the spirit of «Made@ICM», these projects must be 2020 was also a year with three patent filings, thanks mature enough after prototyping to allow industrial to the work of different teams at the Institute. The first transfer and subsequent wide dissemination of inno- is based on findings suggesting that a new medical vation. At the end of 2020, a partnership was signed technology can slow the build-up of amyloid plaques with SBT-HappyNeuron, a French SME specializing in in Alzheimer’s disease. The second, resulting from a digital therapy, to develop projects resulting from a collaboration with academic chemists, demonstrates recent participatory innovation program dedicated the potential for new molecules to act on the neu- to traumatic brain injuries and carried out with the roinflammatory component of neurodegenerative Department of Physical Medicine and Rehabilitation diseases including Parkinson’s disease, using unique of the hospital. Thanks to these new instruments, biological models. The third is about the anticipation CARE LAB is now equipped to support strong deve- of epileptic seizures by electroencephalography. lopment for made@ICM.

The second year of the «Sleeping Beauties» project allowed continued assessment of drugs for thera- peutic purposes in glioblastoma, the most common brain cancer in adults, through new partnerships. The growing number of academic partnerships around this project led to the hiring of an undergraduate professional apprentice. The development of high- throughput phenotypic screening protocols on an automated system will also allow optimization of the volume of molecules tested in the near future.

42 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 43 © Amélie Mourichon. Patrick Tourneboeuf © Amélie Mourichon. Patrick Innovation and knowledge transfer CORNERSTONE #1 : current major societal challenge. CORNERSTONE #3 : PROMOTING In 2020, the number of master’s FOSTERING OPEN BRAIN program enrollments doubled SCIENTIFIC and registration has opened INTERDISCIPLINARY EXCELLENCE to international students. All COLLABORATION SCHOOL courses in the program, including International platform visits, were taught Summer School : BRAIN through distance learning with BRAIN BEE PROGRAM videoconferencing.. TO MARKET This program is an international The “Brain to Market“ Summer neuroscience competition for high School is an annual program com- school students. The Brain Bee’s CORNERSTONE #2 : bining translational neuroscience mission is to help students learn PROMOTING and entrepreneurial training THE PAST YEAR HAS BEEN OVERSHADOWED more about the brain and its basic thanks to intensive training to fos- CLINICAL BY THE PANDEMIC. THROUGHOUT THE functions, neuroscience research, ter new projects, new initiatives and misconceptions about brain RESEARCH and new approaches to neurolo- YEAR, WE WORKED TO MAINTAIN THE disorders. Since 2019, Paris Brain gic and psychiatric pathologies. In TEACHING ACTIVITIES OF THE OPEN BRAIN Institute has been the official orga- STARE 2020, the sixth edition was held nizer of the French national com- remotely on the topic of Multi- SCHOOL TRAINING ORGANIZATION. THIS An introductory educational pro- petition. It was initially scheduled gram for neuroscience for 3rd ple Sclerosis, with 31 participants PERIOD WAS AN OPPORTUNITY TO REALIZE for a face-to-face event in March year medical students. from the following schools : SU, HOW MUCH OUR DAILY LIFE IS CLOSELY 2020, and the team made a point Strate, Epitech, and Collège des of maintaining the event by transi- The program was initially created Ingénieurs. LINKED TO NEUROSCIENCE. AN INCREASING tioning to an entirely remote solu- on a voluntary basis for 5 half- NUMBER OF TRAINING COURSES SEEK tion. Of the 50 participants initially days, and we have now welcomed Masterclass for young registered, on June 5, 35 students 60 students since 2017. Building TO DRAW ON NEUROSCIENCE-BASED researchers from Cusset, Lyon, Paris and Tou- on this success, STARE has be- > ”Writing a scientific/medical KNOWLEDGE IN ORDER TO IMPROVE louse were able to connect simul- come a Teaching Unit within the paper” Masterclass. taneously to perform the tests via Sorbonne University Faculty of TEACHING APPROACHES. This training course was orga- their screens. Matsuko Sano, who Medicine since 2020 and its or- nized with Duc Le (eBioMedicine is home-schooled, is the winner of ganization is developing. The pro- Editor-in-Chief). this edition, Carole Hosono from gram will last 2 weeks with one Lycée Louis le Grand got second session per year. Although the > ”Becoming a PI” Masterclass. 2020 session was canceled due place and Théo Damiati from Ly- This training course was deve- To seize this opportunity, to the pandemic, we actively pre- cée Louis le Grand ranked third. loped to prepare young resear- pared the arrival of 20 students Paris Brain Institute has chers for the ”Research Manager” At the same time, an e-learning within our teams, platforms and selection at INSERM and CNRS placed an emphasis on module on Multiple Sclerosis was incubated companies for 2021. and benefitted from the expe- INVESTING IN DIGITAL LEARNING produced and made available to digital technology to rience and advice Paris Brain Ins- participants to prepare for the DECLIC make Institute discoveries AND EDTECH INTEGRATION titute researchers who have been competition. We are working to Like STARE, DECLIC is a program part of selection committees. adapt this module to different available to as many people 2020 saw an investment in digital technology and the that aims to meet the needs of themes. This marks the start of as possible. integration of EdTech approaches. Our priority has been research staff to become familiar > ”Writing a grant” Masterclass. the deployment of user-centric to maintain access to our events and training while ta- with clinical neurology depart- This training was organized for digital content. king into account the effects of distance learning on par- ments. In collaboration with Me- young researchers preparing grant For the Open Brain School, ticipants (access to content, concentration, memoriza- dical-University teams, we deve- applications, with a special focus on loped an immersion program for 2020 was the year of the tion, need for interactions, understanding, etc.). INTERNATIONAL iMIND EU Marie-Curie Grants. Consequently, Paris Brain Institute has implemented researchers, post-docs and doc- launch of its website, where MASTER’S PROGRAM videoconferencing whenever possible, and the Open toral students that will be tested The iMIND master’s program is an Brain School set up a Learning Management System for at the start of the 2021 school all training activities are international and interdisciplinary program and enrollment monitoring. year. currently listed. Registration two-year program. This master’s Open Brain program is the first of its for the various programs is IN 2020, THE OPEN BRAIN SCHOOL BEGAN THE School kind specifically dedicated to PARIS DIGITAL TRANSITION OF ITS CONTENT. now open ! neurodegenerative diseases, a

44 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 45 44 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT Paris Brain Institute 2020 SOCIAL REPORT

OF 335

WHICH ARE EMPLOYEES THE 734 of the foundation PARIS BRAIN AND EMPLOYEES 399 INSTITUTE’S AT THE INSTITUTE are employees of OUR PUBLIC HUMAN PARTNERS

RESOURCES 130 researchers and teacher-researchers 58 postdoctoral students 76.3% 197 engineers and technicians scientific staff 126 doctoral students 15.3% administrative 62 medical and paramedical staff staff 112 administrative staff 49 interns and apprentices GUARANTEEING THE MOBILISATION DURING THE INTEGRATION AND QUALITY OF COVID-19 PANDEMIC LIFE AT WORK FOR EMPLOYEES 8.4% Mobilised from the start of the Covid-19 pandemic, medical the HR team supported the Institute and its staff The Human Resources team is available to staff at the height of the lockdown on various aspects assist the Institute’s employees in all aspects related to teleworking, remote management, ma- of their integration and daily life: recruitment, 39 nagement of partial unemployment benefits, sick leave, employment law, employment Men leave/childcare, communication (”Com’In HR tips”) NATIONALITIES contracts, remuneration, training, career DISTRIBUTION OF 41% and assistance for international staff. management, international welcome. WOMEN AND MEN In support of the teams, the HR department parti- Women 59% As a research environment of excellence, cipated in the resumption of on-site activity while the Institute works to provide a professional maintaining the telework dynamic in a bid to gua- Training environment that offers the best possible rantee the health and safety of staff: identification working conditions. The quality of life at work, of telework, management of staff in the Covid-19 the fight against harassment, the prevention management system (contact cases and positive of psycho-social risks, the collaborative spirit cases) in conjunction with the Institute’s Covid-19 Investment : 1588.50 and diversity are all values that the Institute referent, prevention of RPS and deployment of psychological support systems (telephone cells, 251,679.20 € hours shares within its teams. 81 partnerships with smartphone applications Mind, of which 198,518.40 € in contributions of training employees and 53,160.80 in registration fees Monsherpa). trained €

46 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 47 Paris Brain Institute BOARD BOARD OF DIRECTORS COMMITTEES GOVERNANCE College of founders Scientific advisory board Management committee and members of the board OF THE Every 5 years, Paris Brain Institute as a joint research unit (UMR) is Decisions are made by Executive • Gérard Saillant, Professor of Orthopaedic assessed on the quality of its research, its organization, its strategy director on the basis of CODIR and Traumatological Surgery, President of and its five-year scientific strategy. Team research projects are recommendations. Paris Brain Institute assessed by the International Scientific Advisory Board (SAB), PARIS BRAIN Executive Director of Paris Brain • Jean Todt, President of FIA, whose mission is to advise the Institute and assist it in defining its Institute and the Joint Research Unit Vice-President of Paris Brain Institute general orientations. After discussion, the SAB submits an opinion • Serge Weinberg, President of Weinberg (UMR) that is taken into account to build the file submitted for evaluation INSTITUTE • Prof. Alexis Brice Capital Partners, Treasurer of Paris Brain by the High Council for the Evaluation of Research and Higher Institute Education (HCERES). Scientific director and Deputy • Jean Glavany, Former Minister Director of the UMR • Jean-Pierre Martel, Attorney • Prof. Bassem Hassan • Michael Shelanski – President of the SAB, Columbia University, New York, USA Medical Director • Dimitri Kullman – ION, University College of London, UK • Prof. Jean-Yves Delattre College of • Gabor Tamas – University of Szeged, Hungary • Prof. Catherine Lubetzki qualified persons • Peter Brown – University of Oxford, UK (since November 2020) • Brad Hyman - Massachusetts Alzheimer Disease Research Center, USA • Philippe Ménasché, Professor of Thoracic Secretary General of Paris Brain UCSF Sandler Institute, San Fransisco, USA and Cardiovascular Surgery at Univerité de • Stephen Hauser - Institute and the Joint Research Unit Paris • Bill Richardson – University College of London, UK (UMR) • Richard Frackowiak, Emeritus Professor at • Helen Mayberg - Center for Advanced Circuit Therapeutics, USA • Corinne Fortin University College London • Christian Buchel - University Medical Centre Hamburg-Eppendorf - • Élisabeth Tournier-Lasserve, Professor of Director of Communications and Department of Systems Neuroscience, Germany Development medical genetics at Université de Paris • Arnold Kriegstein - UCSF, San Fransisco, USA • Jean-Louis Da Costa • Masud Husain – University of Oxford, UK • Michael Heneka – DZNE, University of Bonn, Germany In addition, the Support functions College of management Committee (CODIS) full members steers several institutional and transversal projects. The platforms’ • Gilles Bloch, CEO and representative of expert committee is consulted twice the National Institute for Health and Medical a year on the strategic orientations Research (INSERM) Audit committee • Bernard Poulain, Scientific deputy director of each platform, in line with the & nominations and wages committee THE BOARD OF DIRECTORS of INSB and representative of the National Institute’s overall strategy. • Serge Weinberg, President of the Audit Committee REGULATES THE AFFAIRS OF Center for Scientific Research (CNRS) • Bruno Riou, Dean and representative of • Claire Giry, President of the Nominations and Wages THE INSTITUTE THROUGH ITS • Jean Glavany, Former Minister Sorbonne University Ethics & deontology • Erik Domain, Director of Relations with • Jean-Pierre Martel, Attorney DELIBERATIONS. IT DECIDES ON committee Universities and Research Organisations THE STRATEGIC ORIENTATIONS and representative of Paris Hospital The Paris Brain Institute Ethics PUT FORWARD BY THE GENERAL Administration (AP-HP) and Deontology Committee was MANAGER, VOTES ON BUDGETS established with the dual responsibility Committee for coordination of foundation of contributing to the ethical AND CERTIFIES THE ACCOUNTS. College of and public stakeholder activities conduct of research and compliance IT IS CHAIRED BY PROFESSOR friends of the foundation • Gérard Saillant, President of Paris Brain Institute to the ethical rules of the activities GÉRARD SAILLANTAND HAS 15 • Gilles Bloch, Representative for INSERM that contribute to its production. • Maurice Lévy • Bernard Poulain, Representative for CNRS Its members are in part Institute MEMBERS DIVIDED IN 4 COLLEGES : • Christian Schmidt de la Brélie • Bruno Riou, Representative for Sorbonne University and Pitié-Salpêtrière Neuroscience • Martine Assouline FOUNDERS, QUALIFIED PERSONS, • Erik Domain, Representative for AP-HP Medical University Department FULL MEMBERS (INSERM, CNRS, employees, appointed by the Board of SORBONNE UNIVERSITY, AP-HP) Directors for 3 years, and two external Public commissioner members, one representing patients AND FRIENDS OF THE FOUNDATION. and the other representing donors. • Philippe Ritter

48 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 49 Paris Brain Institute

FOUNDING 5 ADVISORY COMMITTEES MEMBERS

• Gérard Saillant, Professor of THEY ISSUE OPINIONS AND Orthopaedic and Traumatological Surgery, RECOMMENDATIONS BASED ON THEIR President of Paris Brain Institute AREA OF EXPERTISE. • Jean Todt, President of FIA, Vice- President of Paris Brain Institute • Yves Agid, Honorary Professor of The scientific and medical steering Neurology and Neuroscience committee • Luc Besson, Film Director The Scientific and Medical Steering Committee brings • Louis Camilleri, Former CEO of Ferrari together representatives from the 4 research fields (5 • Jean Glavany, Former Minister in 2021). Its mission is to integrate the concerns and • Maurice Lévy, Chairman of the interests of researchers into the Institute’s overall mis- Executive Board of Publicis Group, Co- sion by participating in the development and evolution Chair of the Paris Brain Institute Friends of the scientific strategy, advising the Management Committee Paris Brain Institute Committee, regularly dealing with substantive issues • Olivier Lyon-Caen, Professor of raised by the principal investigators and providing fee- Neurology, former Director of the Nervous dback to researchers in each field. System Diseases Centre of Pitié-Salpêtrière FINANCIAL REPORT University Hospital Teams council • Jean-Pierre Martel, Attorney • Max Mosley, Former President of FIA THOROUGH TRANSPARENCY The teams council, made up of the General Manager • Lindsay Owen-Jones, Honorary and all the team leaders (25 in 2020), meets once a President of L’Oréal, Honorary President of month. It is consulted on the scientific policy, budge- the Paris Brain Institute Friends Committee AT THE CORE OF OUR ACTIONS tary measures and priorities for the UMR. • David de Rothschild, Chairman of the Rothschild Bank & Co Supervisory Board The Social and Economic Committee • Michael Schumacher, Formula 1 Driver The Social and Economic Committee (CSE) represents • Serge Weinberg, President of Weinberg the Foundation’s staff in dealings with the employer Capital Partners, Treasurer of Paris Brain and informs him of any individual or collective com- Institute plaint concerning the application of labour regulations THE ADVANCES AND ACTIONS (Labour Code, salaries, working hours, health and safety, etc.). OF PARIS BRAIN INSTITUTE WERE CARRIED OUT WITH THE UTMOST Laboratory committee TRANSPARENCY, WITH “TRUSTED The mission of the Laboratory Committee is to ad- DONATION” ACCREDITATION SINCE vise UMR management on UMR activities, scientific NOVEMBER 2010 AND RENEWED IN policy, budgetary and human resources policy, and all FRIENDS OCTOBER 2019. THIS ACCREDITATION other questions related to UMR administration. The OF PARIS BRAIN members of the laboratory council are elected by their ATTESTS THAT THE ACTIVITIES OF college (5 colleges in 2020). The number of represen- INSTITUTE ASSOCIATION THE INSTITUTE ARE IN LINE WITH tatives is proportional to the number of members in • Lily Safra, Honorary President, President the college (15 members in 2020). THE COMMITTEE’S PRINCIPLES : of the Edmond J. Safra Foundation STATUTORY FUNCTIONING Committee on gender equity • Gérard Saillant • Jean Todt AND IMPARTIAL MANAGEMENT, The mission of the Gender Equity Committee, which • Lindsay Owen-Jones THOROUGH MANAGEMENT, grew out of the XX initiative at Paris Brain Institute, is • Maurice Lévy QUALITY OF COMMUNICATION to raise awareness of inequalities of opportunity and • David de Rothschild to point out biases, promote the recruitment and pro- • Jean-Pierre Martel AND FUNDRAISING ACTIONS, AND motion of women, act for the visibility of women in • Serge Weinberg FINANCIAL TRANSPARENCY. science and propose training to change practices and culture at the Institute.

50 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 51 FUNDRAISING 2020 FINANCIAL SITUATION

2020 fundraising revenue reached €18.3M. Income Statement by Nature and Function (ISNF) In 2020, the main new patronage agreements Fundraising and communication costs are expenses signed were the following : and Expenditure Statement (ES) 2020 distribution of income incurred to collect funds from individuals (donations • Fondazione Generali-The Human Safety Net and bequests), companies and private foundations New accounting regulations relating to the annual • Fondation d’entreprise IRCEM (patronage and sponsorship actions), as well as com- accounts of private non-profit legal persons require 21% • FIA Foundation munication actions. They represent a total of 4.3 M €, the presentation of an income statement by nature 29% or 10% of total ISNF allocations The Circle of Friends of Paris Brain Institute and function (ISNF) to reflect the economic model brings together donors who have been of the entity and an annual fundraising expenditure Operating costs are expenses in support of research involved since the very beginning of the Paris statement (ES) using the data from the previous in- (general administration, finance, human resources, le- Brain Institute adventure by accumulating come statement. 5% gal, IT and logistics) and represent 6% of total ISNF large donations (€15,000 per year and more). allocations, i.e. € 2.7 M. The purpose of these documents is to give a quick This Circle was created to specifically thank overview of the use that any foundation or associa- the major donors, individuals, companies and 7% tion makes of resources collected from the public foundations, who have been working with the to finance its social missions. The tables presented Institute since 2008. It brings together donors here thus reflect the economic model and social who have donated at least €10,000 in a given 23% 2020 distribution of expenses missions of the Institute. year. At the end of 2020, the Circle of Friends 15% had 578 donors. Since October 2020, the Circle In accordance with accounting regulations, alloca- Income has been co-chaired by Ms. Martine Assouline tion mechanisms underlying the development of and Mr. Maurice Lévy, Founding Member of these statements reflect management and alloca- • Fundraising income Paris Brain Institute. tion rules defined by Paris Brain Institute and are • Public and private subsidies 6% therefore based on distribution keys established Income from technological platforms activities In order to increase its resources, Paris Brain • internally (analytical breakdowns). Allocations are and from research collaborations with industrial partners Institute continued its fundraising campaigns in Funding “IHU program” 84% valued at full cost per destination. • 2020. Paris Brain Institute is particularly grateful Miscellaneous income (rental, re-invoicing of 10% and extends its thanks to loved ones who • charges, financial income) organized fundraising in memoriam benefitting 2020 Income by Nature • Report de ressources antérieures the Institute. Funding of research projects is characterized by a plurality of funding sources with anchoring Expenses in a long-term perspective in order to produce knowledge and major breakthroughs in neuros- 2020 Expenses by Function • Social missions cience. • Fundraising and communication costs Overall 2020 expenses amounted to € 62.2 million : • Operating costs 2020 income amounted to € 63.2 million, including € 45.7 million used in 2020 and € 16.5 million to be € 50.1 million in income for the year and € 13.1 million used subsequently from the allocated resources. Of in carry-over of resources allocated and not used in the 2020 allocations, € 38.2 million were allocated to previous years. Income for the financial year main- social missions, representing 84% of total ISNF allo- ly represents fundraising income (€ 18.3 M or 37%), cations. Allocation of General Public Fundraising which includes donations (€ 11.6 M or 63%), spon- Resources sorship (€ 5.3 M or 29%), bequests and donations Paris Brain Institute social missions include : • Research programs, (1.4 M €, or 8%). Resources collected from the general public used in • Technological platforms, 2020 amounted to € 18.3 M. For every € 100 collected Total income also includes : • Scientific leadership and implementation of interna- from the general public, € 73.8 were used to finance • Income from technological platforms activities tional alliances, social missions and investments, € 23.6 were used to (€ 6.2 M), and from research collaborations with in- • Incubation of innovative businesses. cover the costs of fundraising and communication and dustrial partners (€ 3.4 M), € 2.6 to cover Paris Brain Institute operating costs. • Public and private subsidies (€ 14.3 M), Funding for research projects is primarily dedicated to • Funding of the “IHU program” (€ 4.7 M), nervous system diseases and spinal cord injuries. Tech- nological platforms (neuroimaging, vectrology, geno- • Miscellaneous income (rental, re-invoicing of charges, financial income) €( 3.1 M). typing sequencing, cell culture, histology and bioinfor- matics) support these projects.

52 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 53 Paris Brain Institute 2020 Income Statement by Nature and Function (in €) 2020 Balance Sheet Paris Brain Institute’s cashflow is invested in marketable securities (capitalization contract taken out with leading Including Including EXPENSES BY FUNCTION Total general public INCOME BY NATURE Total general pu- banking institutions, capital-guaranteed and 100% in support blic support Assets (M€) 2019 2020 euro funds). 1. Social Missions 38 181 383 13 002 106 1. Resources collected from the 18 355 192 18 355 192 Fixed net assets 65 63 general public Realizable and available assets 67 86 Voluntary in-kind contributions Carried out in France 38 181 383 13 002 106 Donations free of equivalent - Actions directly carried out 38 181 383 13 002 106 compensation Total 132 149 - Payments to an acting organization in France - - Patronage, donations and > Volunteering : 18 345 385 18 345 385 bequests Paris Brain Institute benefited from volunteer hours du- 11 620 122 11 620 122 Liabilities (M ) 2019 2020 - Personal donations € 0 0 1 440 408 1 440 408 ring the fiscal year, primarily for communication actions. Carried out abroad - Bequests and life insurance policies - - 5 284 854 5 284 854 Association funds 51 55 Total volume is evaluated at 0.6 FTE, or on the basis of an - Actions directly carried out - Patronage - Payments to an acting Fiscal year profit 1,7 0,95 hourly minimum wage, a total amount of € 17 K. - - Other revenue from general organization in France 9 807 9 807 public support Dedicated funds 15 20 > In-kind patronage : 2. Products unrelated to general 2. Fundraising Costs 4 326 986 4 326 986 17 381 014 - Debt 41 41 In 2020, the Paris Brain Institute Foundation benefited public support from in-kind patronage in the scope of its communica- Cost of appeals to the Donations free of equivalent Deferred income 23 32 - tion actions and appeal for public generosity, namely : generosity of the general 4 010 869 4 010 869 compensation Total 132 149 public Corporate patronage - Costs related to canvassing 316 117 316 117 Financial contributions free of • Media space : FIA-Fédération Internationale Automo- 4 728 491 equivalent compensation Comments bile, Groupe Barrière, JC Decaux, Klesia, Richard Mille, Next Radio TV, Media VB, NRJ Global, M6, Lagardère Pu- Other products 12 652 523 - Financial products 6 627 162 blicité, Radio France, France TV, Amaury Media, Canal+, Total investments made by Paris Brain Institute since - Services rendered 3 388 093 BeinSports, Les Echos/Le Parisien, Figaro Magazine, - Other products 2 637 268 its creation amount to € 49 million, dedicated prima- Réseau S4M, Le Bon Coin, Réseau Adikteev, , Réseau 3. Institutional Operational 3. Grants and other public rily to technological platforms that support research. 2 738 510 475 146 14 286 154 Emoteev, Réseau Equipe.fr, Réseau Teads, Reseau Cerise, Costs funding 4. Reversals of provisions and Investments for fiscal year 2020 amount to € 3 million Réseau Madvertise, Réseau Tabmo, Réseau DailyMotion, 4. Provisions & Impairments 454 448 0 73 402 0 impairments and include : Réseau Webedia, Réseau Tf1, Réseau SublimeSkinz, Ré- 5. Use of allocated resources seau Capitfy, Reseau Criteo, Reseau Ogury, 5. Income tax - - 13 078 781 1 502 769 • Investments in scientific materials and equipment from previous fiscal years (€ 1.5 M including 4 microscopes for a total of € 0.75 M), 6. Carryover of fiscal year • Donated products and services : ANACOFI, IDEC, Or- 16 523 021 2 053 723 • Investments to update the IT network (€ 1 M), allocated resources rick Rambaud Martel, Publicis Groupe, ZenithOptimedia. • Continued construction at the Rue du Chevaleret site GRAND TOTAL 62 224 348 19 857 961 GRAND TOTAL 63 174 543 19 857 961 (change in assets in progress). To maintain its level of excellence, Paris Brain Institute SURPLUS OR DEFICIT 950 195 has set up internal and external control procedures to Net fixed assets amount to€ 63 million. As of December guarantee thorough and efficient management: contri- 31, 2020, cash holdings amount to € 40.1 million, inclu- 2020 Expenditure Statement (in €) butions to the Trusted Donations Charter Committee ding € 14 million dedicated to earmarked funding. Asso- and services of an independent auditor. ciation funds of Paris Brain Institute amount to € 55 mil- APPLICATIONS BY FUNCTION 2020 RESOURCES BY NATURE 2020 lion. They include equity for € 33 million supplemented 1. Social Missions 13 002 106 1. Resources collected from the general public 18 355 192 by investment grants of € 22 million. Non-expendable 13 002 106 Donations free of equivalent compensation endowment totals € 1.2 million. At the end of the fiscal Carried out in France 13 002 106 year, dedicated funds (funds still to be committed to - Actions directly carried out Patronage, donations and bequests 18 345 385 0 multi-year programs) amount to € 20 million. - Payments to an acting organization in France - Personal donations 11 620 122 - Bequests and life insurance policies 1 440 408 - Patronage 5 284 854 > Reserve policy Carried out abroad 0 - Actions directly carried out 0 Other revenue from general public support 9 807 When it was created in 2006, the Paris Brain Institute - Payments to an acting organization in France 0 Foundation received an endowment of 11.70 million, € TRUSTED DONATIONS 2. Fundraising Costs 4 326 986 of which € 1.2 million was non-expendable. Thanks to Cost of appeals to the generosity of the 4 010 869 thorough budget management, the Foundation has ba- On November 3rd 2010, Paris Brain Insti- general public lanced its expenses and income for the past 5 years, thus tute received certification from the Trusted Costs related to canvassing 316 117 avoiding drawing on its reserves. Furthermore, the Board Donations Charter Committee. This certifi- 3. Institutional Operational Costs 475 146 of Directors’ investment policy is extremely cautious. cation was renewed in October 2019. For TOTAL APPLICATIONS 17 804 237 TOTAL RESOURCES 18 355 192 over 20 years, this Committee has acted 4. Provisions & Impairments 0 as a regulator: certified organizations must 2. Reversals of provisions and impairments 0 respect ethics rules, implement a stringent 5. Carryover of fiscal year allocated resources 2 053 723 3. Use of allocated resources from previous fiscal years 1 502 769 policy towards donors, and accept on- Resource surplus for the year - Deficit of the general public fundraising of the year - going monitoring of their commitments. TOTAL 19 857 961 TOTAL 19 857 961

54 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 55 Communications and Development AN EXHIBIT TO CELEBRATE THE LIVE S3COVID-19 CONFERENCE INSTITUTE’S 10 YEAR ANNIVERSARY S3ODEON, in association with the Academy of Sciences, SHARING AND Institut de France and Paris Brain Institute, organized To make these 10 past years even more visible, an a special edition of ”S3COVID-19, what does science exhibit was designed to take the public at large say ?”. The conference brought together an exceptional on a discovery of “10 years at the Institute”. With 5 DISSEMINATION panel of 12 key experts. They shared what we know and different themes, this retrospective is an opportunity what we do not know about the virus, insights on mana- to discover Paris Brain Institute’s vision, its ecosystem, gement of the health crisis, and control of the pandemic. OF KNOWLEDGE major scientific and medical findings in the past decade, and major challenges to come in the field of ABOUT THE BRAIN neuroscience. The exhibit is ongoing. PARTNER EVENTS NATIONAL AWARENESS CAMPAIGN Due to the health situation, Paris Brain Institute saw many of its partner events canceled or modified in AND ITS PATHOLOGIES #YOURBRAINMAKESYOUREMARKABLE the way they were held. This was particularly the case for the Course des Héros, or Heroes Race, a #VOTRECERVEAUVOUSRENDREMARQUABLE charity sporting challenge. It took place online for the benefit of Paris Brain Institute. A team of runners To support its recent name change, Paris Brain Ins- from Paris Brain Institute was also been set up for the titute launched a national awareness outdoor media online Paris 20K to support this long-term partner. THE MAIN GOALS OF PARIS BRAIN campaign with the hashtag #votrecerveauvous- rendremarquable, #yourbrainmakesyouremarkable, The Institute also organized 100% online partner se- INSTITUTE’S COMMUNICATION produced pro bono by historical partners Publicis minars such as the Demoday of the Pfizer Healthcare ARE TO SHARE ADVANCES IN OUR and JCDecaux. Through portraits of great persona- Hub France’s second edition. The live conference RESEARCH WITH THE PUBLIC AT lities from the political, sporting, cultural and artis- was hosted by Franck Le Meur, President of Tech- tic worlds, including Simone Veil, Rafael Nadal, and toMed, and brought together all those involved in LARGE AND TO DEVELOP THE even Jean Reno as well as a strong slogan, this cam- the program to look back on this second edition and IMAGE AND ATTRACTIVENESS OF paign aims to make each of us aware of the vital highlight the agile and innovative framework set up importance of this fascinating organ, the most com- by Paris Brain Institute and its incubator iPEPS - The THE INSTITUTE IN FRANCE AND plex in the human body. Healthtech Hub. ABROAD. TO DO SO, WE HAVE The campaign took place in two stages. A first na- FORGED A RELATIONSHIP WITH tional 100% outdoor media plan was implemented throughout France between June and August on BRAINCAST PODCAST : THE MEDIA, SET UP PARTNERSHIPS, 6,500 facings and 5,000 bus stops. In November, a GIVING NEURONS A VOICE, DEVELOPED COMMUNICATION THE BRAIN & SPINE INSTITUTE - ICM second phase of the campaign was carried out on IN COLLABORATION CERVEAU the radio (with the voice of Jean Reno and broadcast CAMPAIGNS, EVENTS AND JOINT BECOMES THE PARIS BRAIN INSTITUTE ! & PSYCHO MAGAZINE on Chérie FM, Europe 1, France Bleu, France Inter, ACTIONS WITH OUR ACADEMIC RMC, RTL, and more) and online (digital banners on In 10 short years, ICM has become a leading neuros- To highlight the Foundation’s influence as an inter- PARTNERS (INSERM, CNRS, AP-HP, 20 Minutes, Atlantico.fr, Aufeminin.com, Télé 7 jours, cience research center in Europe. Thanks to the invol- nationally renowned research institute specializing in Telerama.fr, and more). A “relay” website was also SORBONNE UNIVERSITY, INRIA ...). vement of its 734 researchers, physicians and experts, neurodegenerative diseases, we initiated a partnership launched with the various campaign visuals. many scientific, medical and technological advances with Cerveau & Psycho Magazine. A total of five Brain- have been made possible. To go even further in its deve- The objective was to remind the general public that : cast podcasts with exciting content were recorded lopment, Paris Brain Institute decided to strengthen its with Profs. Yves Agid, Laurent Cohen, Alexis Genin, • The brain is the conductor of our orchestra, our visibility and attractiveness. The Brain & Spine Institute Lionel Naccache and Alexandra Durr and were listened - ICM becomes Paris Brain Institute. A progression, not a organism, and it is thanks to it that we can dream, Despite the pandemic, to nearly 30,000 times in 2020. radical change: we are not letting go of the spinal cord, think, move, write, imagine, speak, create, and more ; the Institute carried out an essential relay that helps an enormous quantity of • Paris Brain Institute needs support to face the noteworthy communications information move throughout the body. We are moving many challenges towards «healthy aging», especially forward towards greater clarity and simplicity as we in- knowing that 1 in 8 people in France are affected by actions for its 10th anniversary crease societal awareness of challenges in neuroscience a brain disease. as well as to promote research, research. Our acronym remains: we have been the Brain COVID-19 efforts, and & Spine Institute for the past 10 years and do not wish to erase our history and the great breakthroughs we achie- recent developments in its ved in nervous system diseases. It is also our way of re- organization. cognising the support of those in our community who have been by ICM’s side from the start.

56 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT Communications and Development To help understand the development of brain diseases Donations to Paris Brain Institute are Watchmakers Richard Mille and that affect 1 billion people around the world, making income tax-deductible up to 66%, F.P.Journe once again decided to sell room for the Institute in your will or designating it as real estate tax-deductible up to 75%, one of their creations to benefit Paris PATRONAGE, the beneficiary of a life insurance contract are powerful and corporate tax-deductible up to Brain Institute, contributing to the accelerators for discoveries that will benefit future 60%. support of research projects. Crédit generations. Mutuel Nord Europe, La Française and The Donor Service can be reached Carole Clément, testator relationship manager, has been Euryale AM renewed their commitment DONATIONS on +33(0)1 57 27 47 56 answering an increasing number of queries from single through the SCPI Pierval Santé sharing or at [email protected] individuals and couples without children, as well as from fund. CIRCLE OF AND donors who wish to extend their commitment. Carole Clément can offer visits to the Institute for Finally, in a time when certain scientific FRIENDS OF experiments were suspended during those wishing to learn more about how researched is PATRONAGE : PARIS BRAIN BEQUESTS organized. She can also coordinate discussions with our the first lockdown, Paris Brain PHILANTHROPY INSTITUTE notary for personalized solutions Institute was able to count on the FOR RESEARCH spirit of understanding of the patrons • Lily Safra, Please feel free to contact her in full confidentiality committed to multi-year agreements Honorary President of the The Paris Brain Institute Circle of who agreed to maintain payments and without any commitment on your part, to share Circle of Friends of Paris Friends brings together Institute despite the research delays. your project, receive answers to your questions or Brain Institute THE SUPPORT OF OUR patrons and major donors. Throughout receive our new bequest, donation and life insurance • Lindsay Owen-Jones, the year, members of the Circle are DONORS (INDIVIDUALS, brochure : Carole Clément at +33(0)1 57 27 41 41 Donors and patrons Honorary President of the offered private visits to laboratories, COMPANIES, FOUNDATIONS or by email: [email protected]. Circle of Friends of Paris scientific and cultural conferences, and committed alongside Brain Institute AND ASSOCIATIONS) AS WELL meetings with researchers. researchers against SARS- • Pr. Gérard Saillant, GENERAL PUBLIC FUNDRAISING Founding Member and AS FROM THE GENERAL PUBLIC The Circle of Friends Office can be CoV-2 President of Paris Brain reached on +33 (0)1 57 27 40 32 IS ESSENTIAL FOR PARIS BRAIN Although 2020 was affected by an unprecedented Institute or at [email protected] Faced with an unprecedented upheaval health crisis, donor support towards Paris Brain Institute • Jean Todt, INSTITUTE TO STRENGTHEN ITS caused by the COVID-19 pandemic allowed for solid and continued growth in the number Founding Member and RESEARCH PROGRAMS, RECRUIT of donations and in general public fundraising, with along with the rest of humanity, Vice-President of Paris Exceptional generosity Paris Brain Institute immediately THE BEST SCIENTISTS, ATTRACT over € 8.53M raised. This represents an increase of 9% Brain Institute compared to 2019. Over the year, we welcomed no less towards the Institute’s appealed to the commitment of • Martine Assouline et YOUNG TALENTS AND MAKE than 25,000 new donors. research programs despite its donors and patrons to support Maurice Lévy, STATE-OF-THE-ART EQUIPMENT the health situation unprecedented research projects Co-Presidents of the Paris There were incredible appeals for donations throughout intended to understand the effects Brain Institute’s Campaign AVAILABLE TO THEM. the year, especially in April with an emergency campaign and neurological complications of the Committee st in connection with the COVID Neuroscience Cohort As of December 31 , 2020, the Circle virus. Along with the support of our • Jean-Luc Allavena • Cédric de Bailliencourt • project. The other highlight of the year was between of Friends of the Institute included donors, researchers also received the Natacha et Jean-Charles November and December with the 578 donors (individuals, foundations loyal support of the FIA and the FIA Decaux • Alexandre annual Discoverers of Hope and companies). The year was Foundation, OCIRP “at the heart of the Desseigne-Barrière • campaign. Actor Guillaume de marked by the arrival of Fondazione family” Foundation and Accuracy. Sylvain Héfès • François Tonquédec, sponsor since 2018, Generali-The Human Safety Net Henrot • Jean-Philippe and IRCEM Corporate Foundation In addition, given the health context, BEQUESTS, DONATIONS was once again the spokesperson Hottinguer • Véronique as patrons. Klesia group (through Paris Brain Institute was forced to for this fundraising campaign de Kepper • Richard Mille AND LIFE INSURANCE cancel its fundraising breakfast at in which all of the Institute’s its institutions Carcept Prévoyance, • Eddie Misrahi • Margaux supporters are called upon to join Ipriac and Klesia Prévoyance), the the opening of the International Primat • Christian Schmidt Thanks to the great generosity of women and men who forces in the hope of fighting brain Bettencourt Schueller Foundation, Contemporary Art Fair (FIAC) at Grand de La Brélie • Sophie have decided to pass on all or part of their assets to the disease. the Edmond J. Safra Foundation, the Palais as well as its biannual fundraising Seydoux • François Institute, bequests and life insurance in 2020 amounted Saint-Michel Fund, Boston Scientific, dinner. However, a fundraising dinner Thomé • Serge Weinberg to € 1.9 million, a 12% increase compared to 2019. This With the aim of optimizing spending and reducing paper UNIM, the Philippe Foundation, Ever was organized in October 2020 at the Members of the Campaign was especially made possible thanks to a life insurance mailings, online media strategy helped increase online Neuro Pharma, IPSEN, the Abeona Monaco Yacht Club in the presence of Committee on December st contract of over € 489,000 for which Paris Brain Institute fundraising by +31% in 2020, bringing the share of online Foundation, Rousselet Group, Barrière HSH Prince Albert II. 31 , 2020 was designated as sole beneficiary by Ms. André G. This collection to 23% of total general public fundraising. The Group and PHARMADOM ORKYN highlights that an increasing number of people perceive other strategic axis for increasing the share of resources renewed their support for research the exceptionality of the Institute’s research model and directly allocated to research lies in the growth of on nervous system diseases by signed put their trust in it. recurring donations made by direct debit thanks to a agreement. These are strategic resources for the Institute: as a reduction in management fees and expenses related to AMBASSADORS public-interest foundation, it is exempt from inheritance solicitation. This recurring donation method increased Michelle Yeoh, actress, tax and 100% of what is transmitted therefore benefits by +15% in 2020. and Jean Reno, actor our 700 researchers’ work directly.

58 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT THANK YOU THANK YOU

MAJOR PATRONS HORIZON • Jean-Paul Baudecroux • ERIC HOLDING • KERIALIS • SOCIETE BOSTON SCIENTIFIC SA • Jacques and Dominique Garaialde • Fernande Benveniste • EVER NEURO PHARMA France • LA FRANCAISE AM • SOCIÉTÉ FRANÇAISE DE • Elisabeth Badinter • GROUPE IDEC • Gérard Bertinetti • Claude Félix • Mr and Mrs François Lafon MÉDECINE ESTHÉTIQUE • Maria Rosa Bemberg • GROUPE PASTEUR MUTUALITÉ • BGC PARTNERS • FERBLANC FUNDRAISING • Bernard Lange • SCLÉROSE EN PANNE • Dominique, Alexandre et Joy • Sylvain and Michèle Héfès • Mr and Mrs Pascal Boileau • Roland Fernet • Bertrand Lavier • SLA FONDATION RECHERCHE Desseigne • François Henrot • Tatiana and Adrien de Boisanger • Emilio Ferré • Martin Lebeuf (SLAFR) • FIA FOUNDATION • Mr and Mrs Alain Joly • Chantal Bolloré • FINETFO SA • Angélique Lenain and Fabrice de • SOCAUSUD • FONDATION BETTENCOURT • Serge Kampf • Irène Bonnet • FONDATION ABEONA Gaudemar • SODEXO SCHUELLER • MALAKOFF MÉDÉRIC HUMANIS • BOREL & BARBEY • FONDATION AIR LIQUIDE • Jean-Jacques Lestrade • SoLidAir’s • FONDATION GROUPE EDF • Christiane Laborie and Roger • Yves Boucheny • FONDATION D’ENTREPRISE IRCEM • LES AMIS DE CAPUCINE • SOPAREXO • FONDATION EDMOND J. SAFRA Lionnet • Micheline Bridèle • FONDATION PLENUM • LIGUE DE FOOTBALL • Claudine Soubrié • FONDATION LILY SAFRA • Alain Mallart - GROUPE • Bucaille Family • FONDATION MARIE-ANGE PROFESSIONNEL • Jean-Cyril Spinetta • FP JOURNE - INVENIT ET FECIT ENERGIPOLE • Gérard Buffiere BOUVET-LABRUYÈRE • LILLY • Yannick Tarondeau • HSBC FRANCE • Dominique and Danièle Mars • Jean and Anne-Marie Burelle • FONDATION ROGER DE • Daniel Louppe • Nicolas de Turckheim • KLESIA - CARCEPT PREV – IPRIAC • ORACLE • Daniel Buren SPOELBERCH • Georges Louviot • Jean-Philippe Thierry • Maurice Lévy • PATHÉ • Louis Camilleri • FONDS DE DOTATION JANSSEN • Pascal Olivier and Ilana Mantoux • Alain Thinot • Docteur Léone-Noëlle Meyer • Jean-Luc Petithuguenin • CAMPENON BERNARD HORIZON • Mr and Mrs Patrick Martin-Michaud • François Thomé • Richard Mille • PHILIPPE FOUNDATION, INC. CONSTRUCTION • FONDS DE DOTATION LIONS CLUB • MAXI SEC • Antoine and Enrica Van Caloen • MSDAVENIR • Christian Poquet • CAPGEMINI LYON DOYEN • Florent Menegaux • Albert Uderzo • OCIRP • RATP • Marella Caracciolo Agnelli • FONDS PATRICK DE BROU DE • Mr and Mrs Bertrand Meunier • UNIM • ORRICK RAMBAUD MARTEL • David de Rothschild • P. and J.P. Carle LAURIÈRE • Claude and Isabelle Montero • Thierry Varène • Lindsay Owen-Jones • SCHNEIDER ELECTRIC • Patrick Charpentier • FONDS SAINT MICHEL • Charles Moore Wilson • Antoine Virgili • PUBLICIS • Claude Sfeir • Suzanne Charpentier • FONDAZIONE GENERALI - THE • Renée Mullie • Yves Rocher • RACE OF CHAMPIONS • SUCRE ET DENRÉES • Dr André Chérot HUMAN SAFETY NET ONLUS • Nestlé France SAS • Yoël Zaoui Family • Edouard and Martine de Royère • Dominique Vizcaino • Mr and Mrs Léon Cligman • Dimitri and Maryvonne Fotiadi • Eric and Hervé Neubauer • 15 anonymous • Michael Schumacher • Serge Weinberg • Alberto Colussi • Marie-Pierre Fournier • Claude Pequart • Jean Todt and Michelle Yeoh • 1 anonymous • COMITE NATIONAL OLYMPIQUE ET • Jean-René Fourtou • ORKYN’ MAJOR DONORS • 1 anonymous SPORTIF FRANCAIS • GALORI TRUST • Gilles and Sylvie Pélisson • ADCY5.ORG BENEFACTORS • CRÉDIT AGRICOLE ILE DE FRANCE • GIULIANI S.p.A • John Persenda PATRONS • ALAIR & AVD • Jean-Patrice and Marie-Anne Dalem • GLAXO SMITH KLINE • Jean Peter • 2CRSI • Marie-José Alfandari • AIR FRANCE • Mr and Mrs Laurent Dassault • Jean-François and Dominique • Luciano Pietropoli • Benoit Abdelatif - Classic Days • Jean-Luc Allavena • Jan Aron Family • DAVID HERRO TRUST Gouédard • Mr and Mrs Patrice Piccon • ACCOR • ALTIUS TEMPORIS • AXA BANQUE • Vicomte Olivier Davignon • GROUPE ROUSSELET • PHILIP MORRIS INTERNATIONAL • ACCURACY • ALVILA • Luc Besson • Danielle Decaux • Mina Gondler • Caroline and Olivier Plantefève • AMAURY MEDIA • Gabriel Roland Amare • Christian and Marie-Claire Blanckaert • Jean-Charles and Natacha Decaux • GROUPE EMERIGE • Jacques Popper • Benoît André • Colette Amram • Olivier Carre • Jean-François Decaux • GROUPE G7 • Claude and Benoît Potier • Christine André • Philippe André • BOLLORÉ • Annette Decroix Lavaur • GROUPE LUCIEN BARRIÈRE • Colette Schumacher • Yvon André and Annette Gellé • Manuel et Marie-Thérèse Arango • BOUYGUES • Ghislaine and Olivier Delattre • GROUPE PRÉVOIR • Elisabeth Ratte • Anne Bardinon • ARTEMIS • Lucienne Collin • Claude Demole • Paul Hermelin • RELAIS & CHÂTEAUX • ARB CONSEIL SAS • ASSOCIATION JEAN-CLAUDE • CRÉDIT MUTUEL NORD EUROPE • Aline Derbesse • Monique Guérinat and FISA • Jean Réno • ASSOCIATION CLUB DES 20 KM DE DUSSE • FÉDÉRATION FRANÇAISE DU • Jean-Louis and Marie-Cécile Dufloux • Christian Haas • Jean-Paul Ringeard PARIS • ASSOCIATION JÉROME GOLMARD SPORT AUTOMOBILE • Michel Duhoux • Mireille and René Hadjadje • Richard Roth • ASSOCIATION DEMAIN DEBOUT • ASSOCIATION PAUL ET PHILIPPE • FONDATION AREVA • Jacques Dumas • Pierre Hanriot • ROTHSCHILD & Cie • ASSOCIATION RMC BFM PERROT • FONDATION ARPE • Jean-Christophe Dumas • Bernard Hayot • Nelly Rouyrès • ASSOCIATION SOGNO DI • ASSOCIATION SPORTIVE ET • FONDATION COGNACQ-JAY • Rena and Jean-Louis Dumas • Jean-Marie and Laurence Hennes • RSI, PROFESSIONS LIBÉRALES ET CAVALLINO CULTURELLE DE L’AIR • FONDATION D’ENTREPRISE • Marcel Dupuis • Marie-Jeannine Jacobson ARTISANS • Mr and Mrs Guy Autran • ASSOCIATION SPORTIVE MICHELIN • Paul Dupuy • Pierre Jardinier • Jean Pierre Sabardu • AXA RESEARCH FUND GYMNIQUE NEUILLY • FONDS DE DOTATION PIERRE • Henri Dura • Anne Jousse • Hubert Saltiel • AXÉRIA PRÉVOYANCE • ASSOCIATION VIVRE À SAINT BERGÉ • Cécile and Christophe Durand-Ruel • Alain Kahn • Claire Sarti • BANQUE PICTET DAMIEN • FONDS DE DOTATION JANSSEN • ELIVIE • kamel mennour • Guy Savoy

60 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 61 THANK YOU THANK YOU

• Jean-Pierre Aubin • Brigitte Chichignoud • GRAND HÔTEL INTER • Gilles de Margerie • Mr and Mrs Jean-Pierre Raynal TESTATORS • Nathalie Aureglia-Caruso • Prince and Princess de Chimay CONTINENTAL PARIS • Mr and Mrs Hervé Margolis • Alain Recoules A very special thank you to the twelve • AUREL BGC • Fabien Chone • Allan Green • Mr Marinopoulos • Simon Robertson men and women who bequeathed • AUTOMOBILE CLUB DE France • Gérard Collet • GROUPE BABILOU • Jean Pierre Martel • Bruno Roger all or a part of their estate in 2020. In • AXA BANQUE • Bertrand Collomb • GROUPE LHOIST • Pierre Martinet • Patrick Roque their honor, the Institute launched a • AXA SA • COMBATTRE LA PARALYSIE • Caroline Guerrand-Hermès • Bruno Matheu • Jean-Jacques Rosa new campaign entitled “Researchers • Nicole Ayanian Schneider • COTY INC. • Jérôme Guerrand-Hermès • Bernard Maurel • Martin Rosdy are not alone in their advances at Paris • Stéphanie and Martin Balas • Mr and Mrs Robert Counoy • Pierre Guichet • MEDTRONIC • Jean Claude Rosenblum Brain Institute”. • BANQUE DE LUXEMBOURG • Antoine and Ariane de Courcel • Vivien de Gunzburg • MERCK SERENO • Pierre Rosenblum • Frédéric Banzet • Charlie Coutouly • Marc Haeberlin • Jean-Claude Meyer • ROTARY CLUB ORLÉANS VAL-DE- Colette A. • François C. • Gérard C. • • Mr and Mrs Pierre-René Bardin • CRÉDIT AGRICOLE CENTRE OUEST • Maria Halphen • MILLE MERCIS LOIRE Andrée G. • Martine L. • Marie-Aline M. • Princess Laure de Beauvau Craon • Mr and Mrs Cromback • Joseph Hamburger • Thierry and Natacha Millemann • Elisabeth de Rothschild • Jacques N. • Jacques R. • Margrit S. • Hubert Beaux • Françoise Crouzet • Bob Harifin • Corinne Millet • Louise de Rothschild • Pierre-Bernard S. • Joseph de Z. • Guy and Denise Bechter • Olivier Dassault • Camille Henrot • Maÿlis de Montgolfier • Aurore and Stéphane Rougeot • François Benais • Jean-Luc Davesne • Brigitte Hidden • Christiane Monnet • Thierry Roussel • Robert Bensoussan • Cécile Defforey • HUNTINGTON ESPOIR OUEST • Gérald Morand • Jean-François Roussely • Claude Berda • Blandine and Philippe Delaunay • Simone Huriot • Daniel Moreau • Mr and Mrs Ruckstuhl PARIS BRAIN INSTITUTE • Patrick Bertrand • Anne-Marie Depours • IMPALA SAS • Hervé de La Morinière • Igor Rybakow VOLUNTEERS • BESINS HEALTHCARE France • Louis Desanges • William Johnston • Yves Néron-Bancel • Angèle Sabardu • BIOCODEX • Danielle Dubuit • Christophe Karvelis Senn • NEUROLIGUE • Mr and Mrs Christian Schlumberger Pascale Des Abbayes • Patricia Brault • • BIOGEN FRANCE SAS • Mr and Mrs Claude Dumas Pilhou • Cyril Kongo • NOVARTIS • SFR Ariane Bucaille • Nicole Fourn • • Jean-Claude Biver • Mr and Mrs Claude Elmaleh • Daniel Kouzo • ODYSSEE REINSURANCE COMPANY • SICA2M Antonio Lopez • Marie-Claude Theguel • Alain and Blandine Bizot • EMERAUDE INTERNATIONAL • Sophie and Frédéric Krebs • Nahed Ojjeh • SORIN GROUP • Annie Wilson • Mr and Mrs Jean de Blanquet du Chayla • Jacques-Arthur Essebag • LA LONGUE ROUTE DES MALADES • Jacques Olivier • SPB • BLB SARL • FONDATION CAP NF DE LA SLA • Jean-Claude Olivier • SPIFIN • BMENERGIE • FONDATION CHRISTINE GOUDOT • Mr and Mrs Patrice de Laage de • ONDRA PARTNERS • Giuliana Spotorno • Mr and Mrs André Bohm • FONDATION SERGE DASSAULT Meux • David Pastel • STADE DE FRANCE The Paris Brain Institute would also • Francis Boileau • EXELGYN SA • Mr and Mrs Antoine Labbé • Daniel Payan • Mr and Mrs Vincent Strauss like to thank the La Poste Group for • Charles de Boisriou • FÉDÉRATION FRANCAISE DE • LABORATOIRE IPSEN PHARMA • Valérie Pécresse • Hubert Taffin de Givenchy the skills sponsorship it has received • Eric Boizel Family TENNIS • LABORATOIRES ECLAIR • Henriette Pentecost and friends from • Claude Taittinger in the person of Anne-Laurence • Mr and Mrs Michel Yves Bolloré • FEDEX CORP • Jean-François Labrousse New Caledonia • Astrid Therond Veyrine, within the Communication • Michel and Agnès Bourgeois • Mr and Mrs Fialip • Mr and Mrs Michel Lacoste • Christophe Perchet • Nicole Toulouse and Development Department • CATHY LEITUS ENDOWMENT • Charles-Henri Filippi • Réjane and Michel Lacoste • Guy Percie du Sert • TRACE ONE over the last four years. Thank you • Mr and Mrs Thierry Bourvis • FINANCIERE CADO • Pauline Lamonica • Jacques Pericchi • Nicolas de Turckheim to Anne-Laurence for sharing her • Jean Bousquet • FINANCIÈRE DE L’ECHIQUIER • Christian Langlois-Meurinne • Laurent Pétin • Mr and Mrs Guy Ullens expertise with the teams, and greatly • Claude Bouygues • FINANCIÈRE POCH • Philippe Lassus • Luciano Pietropoli • Patrick Vegeais contributing to the development of • Renaud Bouygues • Thierry Flecchia • LA TOMATE CONTRE LA DYSTONIE • PMU • Jean Veil strategic resources for the Institute. • Jean-Jacques Branger • FONDATION RUMSEY-CARTIER • Alain Lazimi • Nicolas Poniatowski • VERTU • François Buquet • FONDATION VENTE PRIVÉE • LE CHEVAL FRANCAIS • Mr and Mrs Henri de Ponnat • Corinne and Ramon Villagrasa • Daniel Buren • Philippe Foriel-Destezet • Arlette Le Gall • POTEL & CHABOT SA • VINCI CONCESSIONS • Marie-Noëlle Canu-Duclert • FRANCE GALOP • LES VOILES DE SAINT BARTHES • Philippe Pourchet • Olimpia Weiller • Mr and Mrs Arnaud Caspar • Benoit Gallet • Maurice Lesaffre • Margaux Primat • Georges and Sophie Winter THIS PAST YEAR, PARIS BRAIN • Henri and Michèle Cassin • Florence Gombault • Nicolas Lescure • Pierre Pringuet • XO EDITIONS INSTITUTE WAS HONORED TO • CB RICHARD ELLIS • Mr and Mrs Gilles Gantois • Haim Leshanot • PRODUCTION ET MARCHÉS • Gérard Zimmerlin RECEIVE THE RENEWED SUPPORT • CELIO • Jean Glavany • LIONS CLUB DES ESSARTS • Baudoin Prot • Vanessa Von Zitzewitz OF COMEDIAN GUILLAUME DE • CHAMPAGNE LAURENT-PERRIER • Francis Thomas Gleeson • Jacques and Irène Lombard • Bertrand Puech TONQUÉDEC AS AMBASSADOR • Jean-Bernard Champeau • GLG PARTNERS • L’ORÉAL • Paul Raingold FOR THE HOPE DISCOVERERS • Jean-Paul Charmes • Christian Gloz • Francis Lotigie-Browaeys • Mr and Mrs Patrick Rannou CAMPAIGN. • Amaury and Alix de Chaumont Quitry • Mr and Mrs Gorriquer • Bob Manoukian • Alain Ranval • Dominique Chedal • Mr and Mrs Pierre-Henri Gourgeon • François Manset • Alain Rauscher

62 • PARIS BRAIN INSTITUTE • 2020 ANNUAL REPORT 2020 ANNUAL REPORT • PARIS BRAIN INSTITUTE • 63