Despite intensive research on the causes and pathogenesis of multiple sclerosis (MS), the genetic basis of this common cause of neurological disability is still unknown and the complex immunopathological mechanisms underlying brain injury are only beginning to be understood. To date, no curative therapy is available and none of the existing drugs can stop the neurodegenerative process responsible for disease progression. The NeuroproMiSe project represents a highly focussed and integrated effort to investigate in depth the genetic and mechanistic pathways involved in inflammation-induced neurodegeneration, and exploit this knowledge to develop novel candidate drugs for effective neuroprotective therapy. NeuroproMiSe specific objectives are: 1) To identify the major genes and critical pathways associated with MS and inflammatory neurodegeneration. This goal will be achieved through a comparative genetic approach, using an established animal platform suitable for identification of EAE susceptibility genes, and well-characterized, ethnically homogeneous cohorts of MS patients. Through genomic and proteomic screens carried out in animal disease models, further knowledge will be obtained on genes and molecular pathways involved in inflammatory neurodegeneration. 2) To elucidate essential immunopathological mechanisms of neurodegeneration, focussing on innate and adaptive immune responses and on the use of humanized animal models to define new rational ways of developing disease modifying drugs. 3) To develop novel neuroprotective drugs based on targets validated in animal models. In a first step, new therapeutics targeting critical pathways (Ncf-1, TREM-2, TNFR subtypes, ion channels, glutamate receptors, apoptosis) identified by the applicants will be tested and used in combination therapies. The project is conducted in alliance with four SMEs and has potential for direct transfer of basic research results into clinical studies and economic and society benefits.
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Funding SchemeIP - Integrated Project