NCCR Neuro - Neural Plasticity and Repair (2001-2013)
NCCR Director: Prof. Hanns Möhler (2001-2005), Martin Schwab (2005 - 2013)
Home Institution: University of Zurich
Research in the NCCR and major results
The central goal of the NCCR Neuro was to better understand the mechanisms and causes of neurological diseases and to alleviate the suffering of patients by designing and testing novel therapies for the future. After 12 years, an abundance of key novel insights were obtained in basic science which gave rise to new therapeutic approaches. Successful translations into clinical trials were achieved in the cases of Alzheimer’s disease, spinal cord injury, and robot-assisted neurorehabilitation.
The research structure of the NCCR was determined by its overall topic, Neural Plasticity and Repair. From its inception, eight projects, usually consisting of basic and clinical neuroscientists and frequently an engineering or industrial partner, focused mainly on neural plasticity (stem cells, neuroprotection, plasticity and regeneration) and new strategies for the repair of central nervous system damage (Alzheimer’s disease, stroke, epilepsy, multiple sclerosis and spinal cord injury). Projects in neuro-oncology and neurorehabilitation engineering were added during the course of the NCCR.
Important advances were made in the understanding of brain functions and disease pathology. They included the identification of signaling pathways in neural stem cell fate determination, the formation of new circuits following spinal cord and brain injury as a basis of functional restoration after lesions, the discovery of the presence of antibodies with neuroprotective potential in healthy volunteers, the identification of new inflammatory mediators and cascades in multiple sclerosis and prion protein diseases, and important new insights into the function and plasticity of the animal and human sensory-motor cortexes.
The SNSF funded the NCCR Neuro with CHF 42.8 million. In addition, the University of Zurich and ETH Zurich invested CHF 18 million and CHF 17 million respectively. The participating research groups and institutes contributed more than half of the NCCR budget.
Funding 2001 - 2013
Period Funding sources (CHF) 2001 - 2004 2005 - 2008 2009 - 2012 2001 - 2013 % SNSF funding 13'478'393 14'713'125 14'632'895 42'824'413 18,3 Self-funding by University of Zurich 4'450'181 7'623'011 6'201'672 18'274'864 7,8 Self-funding by ETH Zurich 1'440'175 10'300'307 5'435'518 17'176'000 7,4 Self-funding by project participants 35'798'425 50'724'392 56'592'266 143'115'083 61,3 Third-party funding 2'077'010 4'503'778 5'547'128 12'127'916 5,2 Total 57'244'184 87'864'613 88'409'479 233'518'276 100,0
International standing of Swiss research
29 collaborative projects of NCCR members with external parties in EU framework programmes, 214 joint projects with research institutions in the EU, and 105 with institutions in North America, are indicators of the high reputation and international visibility of the NCCR Neuro. Almost 2000 peer-reviewed publications and more than 3100 presentations at conferences add to that. Five researchers of the NCCR Neuro were awarded an ERC grant in the course of the programme.
Type Number Peer-reviewed articles 1956 Articles without peer review 55 Articles in anthologies 199 Books 34 Reports 14 Total 2258
Structural development – Perspectives for the research domain
To strengthen neuroscience research at its home institutions, the NCCR has established nine new professorships: A new chair for animal imaging at UZH/ETH and eight assistant professorships (clinical multiple sclerosis research, experimental MS research, rehabilitation engineering (two positions), stem cell biology, experimental neurorehabilitation, clinical neurorehabilitation and systems biology of Alzheimer's disease). By the end of the NCCR, four of these assistant professors had received permanent professorships at the home institutions and two at other universities. All assistant professorships were funded by the NCCR Neuro with additional help from industrial partners, foundations and private donors. In addition, two independent junior research groups in proteomics research and super-resolution microscopy were set up.
The establishment of centres of expertise for transgenic technology, analysis of complex behaviors in rodents, cell surface proteome analysis and animal imaging as service platforms for all projects was extremely fruitful in expediting experimental progress and knowledge transfer within the NCCR. The Center for Animal Imaging was opened in 2005 as the first high-field magnetic resonance imaging (MRI) facility for animals in Switzerland. This service platform continued permanently after the completion of the NCCR and is one of the greatest structural achievements of this NCCR
Structural measures Number of professorships created
- 1 new full professor
- 9 new assistant professors
- 3 replacements (i.e. retired professors replaced by professor participating in NCCR)
Junior group leaders
- 2 Junior group leaders
Infrastrukturen / Plattformen
- Center 1 "Transgenesis" (Lead: UZH Zurich, groups from UZH, ETH)
- Center 2 "Advanced Assessment of Rodent Behavior" (Lead: UZH, groups from UZH, ETH, USZ/UZH, Psychiatric University Hospital Zurich)
- Center 3 "Proteomics" (Lead of Center 3 and junior group: ETH)
- Center 4 "Animal Imaging" (Lead: UZH/ETH, groups from UZH, ETH) including Junior Group Ewers (ETH, super resolution microscopy).
- University of Zurich, ETH Zurich, University of Fribourg, EPF Lausanne, University of Bern, University of Basel, University of Geneva, University of Lausanne
- Main industrial partners: Novartis Pharma (Basel), Hocoma (Volketswil/Zurich), Neurimmune (Zurich), BrukerBiospin (Fällanden/Zurich), Merck Serono, YouRehab AG
Knowledge and technology transfer to society and industry
The discovery of the occurrence of antibodies that recognise and initiate clearing of amyloid plaques and tangles in healthy human subjects led to the production of new, therapeutic, recombinant fully human antibodies. A clinical trial in Alzheimer's disease patients was initiated in 2011. The research on the development of antibodies for neurodegenerative diseases will be continued.
A major breakthrough in neuronal regeneration was the discovery of neurite growth inhibitors, in particular the protein NOGO, discovered prior to the NCCR. Its functional blockade by an anti-NOGO antibody was found to strongly enhance functional recovery after spinal cord injury, as demonstrated impressively in rodents and non-human primates within this NCCR. A phase I clinical trial performed in collaboration with Novartis and a European clinical network for para- and tetraplegic patients was completed successfully, showing no side effects. The further clinical development of the anti-NOGO antibody continued after the end of the NCCR.
New robot-assisted training devices were developed by combining novel technologies of sensory-motor rehabilitation with close input from basic physiological sciences and with consideration of clinical requirements. Some of these devices were introduced into the market by spin-off companies, in particular for locomotion and arm movement training for spinal cord injury and stroke patients. The successful inclusion of engineering solutions into neurorehabilitation research is one of the major achievements of this NCCR.
Knowledge and technology transfer
Type Number Filed patents 63 Licences 18 Start-up companies 6 Prototypes, demonstrators 16 Processes, products 14 CTI projects 14
Promotion of young scientists and the academic careers of women
The International PhD Program in Neuroscience of the ZNZ (Neuroscience Center Zurich), established in 1998, became the main instrument for the education and training of young researchers in the NCCR. At the end of the NCCR, more than 240 graduate students were enrolled in total and more than 55% of them were international students. The program was linked to a neuroscience training network of the European Union: the 'Cooperation in Research and Training for European Excellence in the Neurosciences' (CORTEX) of EU FP6 from 2005 – 2009, and after 2010 it participated in the Erasmus Mundus Joint PhD Program in Neuroscience with four European partners.
In spite of equality measures on several levels (e.g. personal mentoring, day care offers), the ratio of men to women on the different hierarchical levels has remained more or less constant over the duration of the NCCR. As in many other fields, the percentage of female scientists drops dramatically beyond the postdoc level.
227 PhD theses had been completed by the end of the NCCR Neuro; 80 were still in progress.