Final Activity Report Summary - NSR (Nervous System Repair) Neurodegenerative diseases and injuries that affect the central nervous system (CNS) neurons present a formidable clinical, human and economic challenge for the community. They are difficult to address because adult CNS neurons cannot be replaced by cell division and their axons have only a poor ability to re-grow. This network, based on the recruitment of 16 early-stage researchers (ESRs) in eight of the European leader research centres, aimed at challenging these pathologies on both cellular and systemic levels in an orchestrated effort so as to develop treatments preventing degeneration and enhancing repair of the nervous system. ESRs were engaged in a Ph.D. program and, therefore, a strong effort was put on training and transfer of knowledge activities. There were four interconnected programmes, tackling complementary aspects of nervous system degeneration and repair, i.e. Parkinsons disease (PD), amyotrophic lateral sclerosis (ALS), Huntingtons disease (HD) and spinal cord injury (SCI). ESRs developed and used combinations of animal disease or injury models, embryonic stem cells cultures and grafting, viral vectors and short hairpin ribonucleic acid based (sh-RNA-based) gene expression inhibition to advance knowledge in mechanisms of degeneration and repair. The first dealt with the use of stem cells to increase plasticity or replace cells in disease. The main achievements concerned the characterisation of the conditions leading to precise phenotypes in vitro or in vivo, i.e. after grafting, starting from embryonic stem (ES) cells or precursor cells. The two most innovative findings were: 1. the demonstration that age and cell origin would determine how successful the integration of these new cells would be in the host tissue 2. the fact that Schwann cells derived from ES cells could promote recovery after spinal cord injury in rats. The second programme dealt with a better assessment of the neuroprotective effects of individual or combined factors and proteins. The main finding was that the glial cell-derived neurotrophic factor (GDNF) was an essential factor for the maintenance of a functional nigrostriatal nervous system. Programme three focussed on the basic mechanisms and technology improvements in neuronal regeneration. The most interesting observation was that the failure of axonal regeneration leading to the formation of retraction bulbs at their extremity was due to a disorganised microtubules skeleton. These results opened a new therapeutic avenue for axonal regrowth strategies. Finally, programme four was devoted to study and development of animal models for neurodegenerative disease and therapeutic approaches to counter them. The principal achievement in PD was to show that expression of a truncated form of alpha-synuclein with a fast aggregation rate was sufficient to induce PD symptoms without dopaminergic neuron death. The phenotype was found to be related to problems in the synaptic machinery. For HD, the most interesting observation was that both patients and mice models showed increased metabolism and thirst. In addition to 22 published papers, ESRs participated and presented their work in 62 meetings in total. A number of the ESRs results opened new therapeutic possibilities that would eventually be assessed. Moreover, in terms of social development, ESRs were meeting not only senior scientists, but also directors of companies, medical doctors, patients and families of patients during the eight workshops that were organised throughout the three project years. This broadened without doubt their view about the aims of research and contributed to develop more open-minded scientists. This network definitely provided future researchers with an outstanding training and scientific environment, for which they were very grateful and appreciative to the European Community.
