The main objective of the Action is to promote a scientific and medical interactive European effort in the multidisciplinary field of myelin-related pathologies in order to develop new therapeutic strategies for the largest number of patients. Synergies are critically important for progress in the field. Although the frequency of all leukodystrophies is estimated to be around 1/8000, every single disease is rare. Generation of meaningful, in particular clinical data therefore depends on the interaction of groups form various countries contributing their data and knowledge about specific diseases to a common network. For this purpose the MYELINET Action is to gather at the appointment of the COST Action 33 research and medical groups from 11 Europeans countries covering various aspects of cell biology, genetics, transcriptomics, proteomics, neuro-imaging and development of therapeutic interventions in myelin disorders. The objectives to reach by this multidisciplinary approach are to: – Identify the cause of leukodystrophies of undetermined origin and gain a better understanding of disorders related to myelin loss or failure of development; – Explore the pathophysiological pathways involved in such pathologies; – Discover of novel biomarkers to act as diagnostic/follow up tools or drug targets; – Develop, validate and use new diagnostic and prognostic tools; – Promote drug development and inovative therapeutic strategies; – Debate ethical and societal implications and concerns; – Disseminate scientific data and information to the public. 1. Identification of the causes and exploration of the pathophysiological pathways These two objectives are the first research steps required to make significant therapeutic advances for all types of white matter disorders. The COST Action is to provide exchange of knowledge and technical tools already developed at the European level to support the group of white matter diseases in which research is less advanced, particularly white matter disease of the premature, or leukodystrophies recently identified or of undetermined origins. The inter-disciplinary Action of MYELINET is also to promote the scientific progress which has already been made in recent years for other groups of myelin diseases as MS and several leukodystrophies (ALD, MLD, PMD). A key point for direct application of research to human pathology is the possibility to select homogeneous and well phenotyped groups of affected patients/families not only for genetic studies (identification of responsible genes in monogenic leukodystrophies, identification of genetic variants contributing to phenotypic variability) but also to correlate results obtained in cellular and animal models with human pathology. The critical mass which is aimed to be provided through the COST Action is particularly important. The discovery of new genes in leukodystrophies or of new physiopathological mechanisms is an important objective not only for the families individually affected by the corresponding disease, but also for the whole scientific and medical community working in the field of glial cell biology and white matter diseases. Achieving a critical mass of scientists in this field will help to decipher the important role of unsuspected molecules and cellular pathways to unravel the complexity of the white matter physiology and impairment in acquired and genetic diseases of white matter. 2. Discovery of novel biomarkers to act as diagnostic and prognostic tools and develop new drug targets The active development of microarray and bioinformatic technology during this last 5 years has provided major progress in the possibilities to screen in humans as well as in animal models the whole genome (genomics) and all the transcripts produced or regulated by these genes (transcriptomics). Moreover, the possibilities to fractionate proteins (proteomics) produced or regulated by these transcripts in cell or tissue extracts, or in various biological fluids (urine, plasma, serum, cerebro-spinal fluid) have provided additional perspectives towards diagnosis and treatment. Identification of biomarkers for known pathophysiological conditions like cancer is now routinely used in clinics. These new “screening tools”, however, use expensive technologies and equipment and require a critical mass of expertise. In the field of myelin orphan diseases, the COST Action supports a coordinated Action to define at the European level the existing state of the art facilities for a more efficient access and sharing of data as well as the need to develop new technical platforms. The exchange between participants through the COST Action will optimize the transfer of results from animal or cellular models to human or vice versa the validation of the results found in humans to animal models. Involvement of European Biotech companies in the Action will facilitate the rapid application for diagnostic purposes. 3. Promotion of drug development and innovative therapeutic strategies Fundamental research has brought new hopes in myelin related disorders by demonstrating the potential of stem cells and numerous molecules to regenerate the myelin sheath and the axon. The COST Action will stimulate scientific and technological interactions with the aim to focus the efforts toward clinical applications in white matter disorders. High throughput screening of libraries of compounds is now possible using cellular or yeast models allowing a selection for those with potential therapeutic interest that can then be tested in cellular and animal experimental paradigms. Cellular factory platforms are also needed to expand and characterize cells with regenerating capacities for myelin and axons. As for genomic, transcriptomic and proteomic research, access to technical platforms more specifically dedicated to the COST consortium will facilitate and accelerate the design of new drugs and cellular products and their approval for clinical applications. The development of therapeutic drugs that include cell therapy products for human disease is a long process. It requires optimizeation of tests to be done in animal models relevant for the pathology according to protocols closest to conditions required for human clinical trials. Synergism between research, technological and medical groups established through this COST Action will greatly help to bring the gap between proof of concept, drug design and the development of the first clinical trials evaluating the safety and efficacy of these new therapeutic products. 4. Debate ethical and societal implications and concerns of results and assure their scientific dissemination Advances in life sciences and biotechnology should be developed in a responsible way in harmony with ethical values and societal goals. This concern is particularly important in gene testing and innovative therapeutic technologies using new molecules or regeneration/reparation of human brain. MYELINET is dedicated to a large group of devastating orphan diseases with severe functional and vital prognosis. This requires even stronger coordinated actions for responsible, science based and people centred policies on ethical basis. Interactions between patients and their families with medical and research groups have largely demonstrated their effectiveness for this purpose. Active involvement of a non-for-profit research foundation (ELA Foundation) which has narrow links with patients and families affected by genetic leukodystrophies at a European level will strongly support this objective in the COST Action. Patients and relatives will directly benefit from the information dissemination program. Scientific dissemination of knowledge in a coordinated, accessible and multidisciplinary approach is to provide benefit to: – Researchers in the field No regular meeting devoted to orphan myelin diseases in the scope of the MYELINET Action exists at the European level. Involvement of many MYELINET participants to EC integrated projects devoted to specific myelin diseases will facilitate this scientific dissemination. The MYELINET Action will play a precursor entrepreneurial role for subsequent European grant applications, particularly for the FP7 program – New scientists An important aim of MYELINET COST Action is to attract young scientists in the innovative field of therapy of brain disorders but also to teach them new technologies using genomic, transcriptomic, proteomic, NMR, stem cells, screening of libraries of compounds. Established scientists in completely different fields will be another scope of this COST Action. New ideas tend to emerge at the junction of specialisation. Training across disciplines and specialisation is to be promoted including the potential for take-up of information and communication technologies through one of the SME involved in the Action. Synergisms will emerge with the development of new research and communication programs. – European biotechnology SMEs or pharmaceutical companies The MYELINET Actions must take the capacity to translate knowledge from research into new products, processes and services for patient benefits. The MYELINET inter-disciplinary Action, aims not only to prevent and cure specific diseases such as white matter disease of the premature and leukodystrophies, but also to serve as a seed to extend validated strategies (in particular myelin repair) to other myelin disorders such as MS and spinal cord injury in collaboration with biotechnology and pharmaceutical companies. The critical mass of patients registered according to consensus protocols and analysed using innovative diagnostic/prognostic tools serves as the best assets. The critical mass of patients registered according to consensus protocols and analysed using innovative diagnostic/prognostic tools will be constitute the best assets. – Patients and their families Major aspects of the dissemination activities also focus on exchange of information with affected patients and their families. This is to include the organisation of information days open to a broad audience in the frame of annual meetings, communication with the media and documentation made available through the MYELINET web-site (see http://www.myelinet.eu). In conclusion, MYELINET will link scientists, medical doctors, patients and families to talk and learn from each other, providing an international collaborative network that will bring together experts in neurology, neurosciences, genetics, experts in gene analysis, protein, NMR, drug discovery and drug development. The Action will leverage investigation of myelin diseases, identify new drug and diagnostic targets, stimulate the development of innovative therapeutic approaches. It will contribute to the medical scientific, economic and social development of Europe and strengthen Europe’s competitiveness.
