Research in Neurosciences,

A European Perspective

Peter Paul De DeynScientific Director Institute Born-Bunge

The Network of European Neuroscience Schools (NENS) was founded in 2003 and represents over 150 of those graduate schools and programmes across ca. 30 European countries that offer Masters, MD, PhD and doctoral degrees in neuroscience. NENS is a formal structure within the Federation of European Neuroscience Societies (FENS).

The Network of European Neuroscience Schools

The Network of European Neuroscience Schools (NENS) was founded in 2003 and represents over 150 of those graduate schools and programmes across ca. 30 European countries that offer Masters, MD, PhD and doctoral degrees in neuroscience. NENS is a formal structure within the Federation of European Neuroscience Societies (FENS).

The Network of European Neuroscience Schools

European network for interdisciplinary discussions of the social implications of the neurosciences. Funded by the European Science Foundation

European Neuroscience and Society Network

The Network of European Neuroscience Schools (NENS) was founded in 2003 and represents over 150 of those graduate schools and programmes across ca. 30 European countries that offer Masters, MD, PhD and doctoral degrees in neuroscience. NENS is a formal structure within the Federation of European Neuroscience Societies (FENS).

The Network of European Neuroscience Schools

The Network of European Neuroscience Schools

Publication Analysis 1997-2008Clinical Neurosciences

The strategic guidance for our funding of brain research is the 7th Framework Programme on Research and Technical Development (FP7) implemented through so-called Specific Programmes (SPs). Health research in general and brain research in particular is implemented in the Specific Programme Cooperation. Support for infrastructures is provided through the Specific Programme Capacities. The well-established Marie-Curie fellowships are funded through the Specific Programme People and the European Research Council is funded through the Specific Programme Ideas.

European Commission – Health Research - Brain Research

Brain research is supported in the Seventh Framework Programme (FP7; 2007-2013), which includes an activity on ‘Research on the brain and related diseases’ under the theme ‘Health’. This activity has a particular emphasis on translational research, meaning translation of basic discoveries into clinical applications. In the first three FP7 calls, 30 projects were funded under this activity for a total of EUR 135 million. Research relevant to the brain and the nervous system is also addressed in other areas of the current ‘Health’ theme, where an additional 49 research projects received funding for about EUR 247 million.

European Commission – Health Research - Brain Research

Promoting Breakthrough Therapies

across EuropeMichel Goldman, MD,PhD

Executive Director

Belgian Brain Congress 2010

Innovative Medicines Initiative:the Largest PPP in Life Sciences R&D

2 Billion Euro

1 Billion €1 Billion €

Public PrivatePartnership

IMI: Topics for the First Call

1. Improved predictivity of immunogenicity 13m/ 5y 2. Non-genotoxic carcinogenesis 2.5m/2y plus 10m/ 3y 3. Expert systems for in silico toxicity prediction 5m/ 5y4. Improved predictivity of non-clinical safety evaluation 10m/ 3y 5. Qualification of Translational safety biomarkers 21m/ 5y6. Strengthening the monitoring of benefit/risk 15m/ 5y7. Islet cell research 10m/ 5y8. Surrogate markers for vascular endpoints 20m/ 5y9. Pain research 7.5m/ 5y10. New tools to develop novel therapies in psychiatric disorders 10m/ 5y11. Neurodegenerative disorders 7.5m/ 5y12. Understanding severe asthma 12.5m/ 5y13. COPD Patient Reported Outcomes 2m/ 1y + 8m/5y14. European Medicines Research Training Network 5m/ 7yn Safety sciences for medicines training programme 3m/ 5y1. Pharmaceutical medicine training programme 4m/ 5y2. Integrated medicines development training programme 3m/ 5y3. Pharmacovigilance training programme 3.5m/ 5y

EFPIA Commitment: 172.5m Euros, typical project ~15m, 5-10 EFPIA partners/project, majority of 5y duration

IMI: Neurodegenerative Disorders

Bridging the preclinical /clinical

Clinical outcome studies in the neurodegeneration area are notoriously long and expensive. In order to accelerate the successful development of molecules for the treatment of Neurodegenerative disorders, it is essential to improve the predictive value of animal models, identify pharmacodynamic markers of drug response, pharmacodynamic models that allow early prediction of efficacy and markers to aid stratification of the patient population. The success of this will be dependent on the partnership of preclinical and clinical scientists to adopt an integrated approach to ensure effective translation of efficacy from bench to bedside andvisa versa. This translational science/medicine approach will allow the rapid identification and accelerated development of successful candidate molecules as well as terminating efforts earlier on those unlikely to offer clinical benefit.

IMI Projects on Brain Disorders

Alzheimer’s diseasePilot project: Addneuromed

Ongoing project: Pharmacog (total budget: 27.7 M €)

Schizophrenia and depressionOngoing project: Newmeds (total budget: 24.0 M €)

Autism Call for Proposals to be released end October 2010

Prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development.

PHARMA-COG

Area 4.2 - Support to policies

HEALTH-2010.4.2-8: Coordination action in support of the implementation by participating States of a Joint Programming Initiative for combating neurodegenerative diseases, in particular Alzheimer's disease. Following the Commission's Communication on Joint Programming to tackle Europe's major societal challenges, the Competitiveness Council, called for a common commitment of EU Member States (MS) to fight Alzheimer's disease and other neurodegenerative diseases. The successful coordination action must support the implementation of a pilot Joint Programming Initiative by proposing innovative ways of pooling national expertise and resources and establishing closer and robust collaborations among the participating States in the field of neurodegenerative diseases, in particular Alzheimer's disease. Applicants must be national/regional agencies and/or ministries funding activities related to neurodegenerative diseases.

Funding scheme: Coordination and Support Action (Coordinating Action).

Description and scope of topic 4.2-8:

The European Brain Council (EBC), established in 2002, involves all major European organizations involved in brain-related issues ranging from scientific and clinical societies, to industry and patients organizations. EBC - together with its member organizations – promotes brain research in Europe; this will lead to new therapeutic and diagnostic tools and together with improved education and information. An important goal is to improve the quality of life of those European citizens living with brain-related diseases as well as of their carers.

I: Development, plasticity & ageing of the brain in health & disease  II. Mind – brain relationship and mental disorders  III. Degeneration & repair in the Brain IV. Revealing pain mechanisms & their control V. Rehabilitation, psychological care & prevention  VI. Sensory systems & autonomic disturbances VII. Towards a better diagnostic & therapeutic approach: enabling technologies

Vision UA

Institute Born-Bunge

Institute Bunge (clinic and research) : 1934-1962-1979

“.. In order to establish a center for surgical and medical research where full diagnostic research could be combined with scientific research.”

Travaux de l’Institut Bunge Vol I, 1936. Born-Bunge Foundation (research) :

1963-2004 Institute Born-Bunge (research) :

from 2005

Ludo van Bogaert and Charles Poser 1955

Prof. Armand Lowenthal1919-2001Intrathecal IgG synthesis in MS

Micro-Eletrophoresis in Agar Gel of Proteins of the Cerebrospinal Fluid and Central Nervous System 1959. D. Karcher, M. van Sande and A. Lowenthal. Institute of Tropical Medicine, Antwerp, and Institute Bunge, Berchem Antwerp, Belgium Journal of Biochemistry 1959; 4: 135-140

Prof. Armand Lowenthal

Prof. J.J. Martin

Neurometabolic storage diseases (together with Prof. Ceuterick-De Groote)Neuromuscular disordersDetailed anatomical study of the thalamusNeuropathological study of dementia

Brief presentation IBB Laboratories and groups

Laboratory for Electrobiology

Laboratory for Neurobiology

Laboratory for Theoretical Neurobiology

En: Ongoing research on the physiology of brain-computer interfaces

Laboratory for Neurochemistry & Behaviour

Laboratory for Neurochemistry & Behaviour

Laboratory for Neurochemistry & Behaviour

Reference for Biological Markers of Memory disorders

LNG: Behavioural research and pharmacological modulation in rodent models of dementia

Van Dam D. & De Deyn P.P. Drug development in dementia: the role of rodent models. Nature Reviews Drug Discovery (2006)

IBB- Laboratories for Neurogenetics

Three research groups active in the investigation of complex neurological diseases of the peripheral and central nervous system

Peripheral Neuropathies Vincent Timmerman

Neurogenetics Peter De Jonghe

Neurodegenerative Brain diseases Christine Van Broeckhoven

Peripheral Neuropathy group

About nerves, pedigrees and genes

Neurogenetics group

IBB- Neurodegenerative Brain diseases Group

Frontotemporal Dementia with Ubiquitin-positive inclusions

Key publications Cruts,M., Gijselinck,I., van der Zee,J., Engelborghs,S., Wils,H., Pirici,D., Rademakers, R.,

Vandenberghe,R., Dermaut,B.,Martin,J-J., van Duijn,C., Peeters,K., Sciot,R., Santens,P., De Pooter,T., Mattheijssens,M., Van den Broeck,M.,Cuijt,I.,Vennekens,K., De Deyn,P.P, Kumar-Singh,S., Van Broeckhoven,C. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21, Nature, 442(7105):920-924 (2006)

van der Zee,J., Rademakers,R., Engelborghs,S., Gijselinck,I., Bogaerts,V., Vandenberghe,R., Santens,P., Caekebeke,J., De Pooter,T., Peeters,K., Lübke,U., Van den Broeck,M., Martin,J-J., Cruts,M., De Deyn,P.P., Van Broeckhoven,C., Dermaut,B.: A Belgian Ancestral Haplotype Harbors a Highly Prevalent mutation for 17q21-Linked Tau-negative FTLD. Brain 129(4): 841-852 (2006)

Pirici,D., van der Zee,J., Vandenberghe,R., Rademakers,R., Dermaut,B., Cruts,M., Vennekens,K., Cuijt,I., Lübke,U., Ceuterick,C., Martin,J-J., Van Broeckhoven,C., Kumar-Singh,S.: Characterization of ubiquitinated intraneural inclusions in a novel Belgian FTLD family. Journal of Neuropathology & Experimental Neurology 65(3): 289-301 (2006)

IBB- Neurodegenerative Brain diseases Group

FTDU-17 gene is progranulin

PGRN is located at 17q21.32, 1.7 Mb centromeric of MAPT

Growth modulatory activity Role in several physiological and pathological

processes (development, wound repair, inflammation and tumorigenesis)

Cysteine-rich polypeptide7.5 x 12-cysteine granulin motif

Function in brain?

gDNA0 1 2 3 4 5 6 7 8 9 10 11 12

UTR

UTR P G F B A C D E mRNA593 codons

Baker et al. and Cruts et al. Nature 2006

Laboratory for Ultrastructural neuropathology & Biobank

IBB BIOBANKCo-ordinator: PP De Deyn

BrainNeuromuscular specimens / skin

Cerebrospinal fluidBlood - plasma - serum

DNA, Cell culturesHuman & animal

Task Forces

Neuromuscular Disorders

Responsible: C. CeuterickP. De Jonghe/ V. TimmermanK. Claeys, L. HeytensConsultant: J.J. Martin(NMRC UZA, LUN)

TF 1

Prion Diseases

Responsible: P. Cras

(Lab. of Neurobiology)

TF 2 CNS NeurodegenerativeDisorders (dementia/park)Responsibles: C. Van Broeckhoven &PP. De Deyn

S. EngelborghsS. Kumar-SinghConsultant: J.J. Martin(LNG, LNB)

TF 3

Impact factors of IBB publications in 2009

IBB Publications 2009

impact factors

no IF 0-2 2-4 4-6 6-8 8-10 > 10

nu

mb

er

of

pu

blic

atio

ns

0

5

10

15

20

25

30

35 published (n=78)in press (n=14)

total n=92