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Research in Neurosciences, A European Perspective Peter Paul De Deyn Scientific Director Institute Born-Bunge 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 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). European Neuroscience and Society Network European network for interdisciplinary discussions of the social implications of the neurosciences. Funded by the European Science Foundation 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 Publication Analysis 1997-2008 Clinical Neurosciences European Commission – Health Research - Brain Research 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. Promoting Breakthrough Therapies across Europe Michel 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 € Public 1 Billion € Partnership Private IMI: Topics for the First Call 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. Improved predictivity of immunogenicity Non-genotoxic carcinogenesis 2.5m/2y plus Expert systems for in silico toxicity prediction Improved predictivity of non-clinical safety evaluation Qualification of Translational safety biomarkers Strengthening the monitoring of benefit/risk Islet cell research Surrogate markers for vascular endpoints Pain research New tools to develop novel therapies in psychiatric disorders Neurodegenerative disorders Understanding severe asthma COPD Patient Reported Outcomes European Medicines Research Training Network Safety sciences for medicines training programme Pharmaceutical medicine training programme Integrated medicines development training programme Pharmacovigilance training programme 13m/ 5y 10m/ 3y 5m/ 5y 10m/ 3y 21m/ 5y 15m/ 5y 10m/ 5y 20m/ 5y 7.5m/ 5y 10m/ 5y 7.5m/ 5y 12.5m/ 5y 2m/ 1y + 8m/5y 5m/ 7y 3m/ 5y 4m/ 5y 3m/ 5y 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 and visa 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 disease Pilot project: Addneuromed Ongoing project: Pharmacog (total budget: 27.7 M €) Schizophrenia and depression Ongoing 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 Description and scope of topic 4.2-8: 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). 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 Lowenthal 1919-2001 Intrathecal 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 disorders Detailed anatomical study of the thalamus Neuropathological study of dementia Brief presentation IBB Laboratories and groups Laboratory for Electrobiology Laboratory for Neurobiology Laboratory for Theoretical Neurobiology En: Ongoin g research on the physiology of brain-computer inte rfaces 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 Neurodegenerative Brain diseases Group IBB- 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, KumarSingh,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): 841852 (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., KumarSingh,S.: Characterization of ubiquitinated intraneural inclusions in a novel Belgian FTLD family. Journal of Neuropathology & Experimental Neurology 65(3): 289-301 (2006) FTDU-17 gene is progranulin 0 1 UTR 2 3 P 4 G F 5 6 B 8 7 A C 9 D 10 E 11 1 UTR gDNA 2 mRNA 593 codons 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 polypeptide 7.5 x 12-cysteine granulin motif Function in brain? Baker et al. and Cruts et al. Nature 2006 Laboratory for Ultrastructural neuropathology & Biobank IBB BIOBANK Co-ordinator: PP De Deyn Brain Neuromuscular specimens / skin Cerebrospinal fluid Blood - plasma - serum DNA, Cell cultures Human & animal Task Forces TF 3 TF 1 Neuromuscular Disorders Responsible: C. Ceuterick P. De Jonghe/ V. Timmerman K. Claeys, L. Heytens Consultant: J.J. Martin (NMRC UZA, LUN) TF 2 Prion Diseases Responsible: P. Cras (Lab. of Neurobiology) CNS Neurodegenerative Disorders (dementia/park) Responsibles: C. Van Broeckhoven & PP. De Deyn S. Engelborghs S. Kumar-Singh Consultant: J.J. Martin (LNG, LNB) Impact factors of IBB publications in 2009 IBB Publications 2009 35 published (n=78) in press (n=14) number of publications 30 25 total n=92 20 15 10 5 0 no IF 0-2 2-4 4-6 impact factors 6-8 8-10 > 10