0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

EC.11 – Neuroprotective strategies for multiple sclerosis
P24 – Smith/ION UCL (University College London ION), United Kingdom –
Moving to UCL at month 25 – Competence: Axonal pathology in demyelinating
and neurodegenerative CNS diseases, ischemia and NO-mediated neurotoxicity.
Role in the Project: Testing of sodium channel and sodium/calcium
exchanger blockers in in vitro and semi-in vivo spinal cord preparations; electrophysiological
and morphometric studies; focal demyelinated lesions. In
vivo confocal spinal cord imaging methods in EAE.
P25 – R. Diem/USAAR (University of Sarlaand), Germany – Moving from UK-
GOE to USAAR at month 27 – Competence: Analysis of neuroprotective compounds
acting on ion channels. Role in the Project: Animal model of MS with
optic nerve degeneration; analysis of apoptotic pathways in neurons; electrophysiological
techniques.
P26 – Battistini/FSL (Fondazione Santa Lucia), Italy – Competence: T cell
biology Autoimmunity Immunopathology of MS. Role in the Project: Multiparametric
flow cytometry; cell sorting. Phenotypic and functional characterization
of EBVspecific T cells. Culture of T cell lines and clones.
PROJECT OBJECTIVES
The overall aim of the NeuroproMiSe project is to elucidate the molecular
mechanisms underlying inflammation-driven injury of the central nervous
system (CNS) and to define novel targets, validated in animal models, for the
development of therapeutic strategies for highly debilitating neuroimmune
diseases. NeuroproMiSe will achieve this goal through a disease-oriented
approach by identifying the essential genes and critical pathways leading to
multiple sclerosis (MS), the most common inflammatory disease of the CNS.
Given the importance of axonal damage and neuronal loss in determining
clinical deterioration in MS patients and the lack of effective therapies for
prevention of MS progression, the project is strongly oriented towards achieving
a better understanding of the molecular basis of neurodegeneration, and
direct protection of axons/neurons through targeting of critical signaling pathways.
The knowledge and products generated in this project may also have
implications for the pathogenesis and therapy of other acute and chronic neurodegenerative
diseases with an inflammatory component.
The major, specific NeuroproMiSe objectives are the following:
1 – To identify candidate genes involved in CNS tissue destruction in MS
and animal models of neuroinflammation and neurodegeneration, and decipher
their pathophysiological role. This goal will be achieved through:
a) A ‘disease-driven’ strategy, that will allow to identify genes and pathways
associated with disease susceptibility and course in animal models of
MS and neurodegeneration, and to use this information to define synonymous
genes in homogeneous and well characterized cohorts of patients with
MS and population-based controls. The unique animal platform of mouse and
rat congenic strains established by P3 and P8 will be used for identification of
diseasesusceptibility genes and associated molecular pathways (first results
expected by month 18), and for the study of gene-gene and gene-environment
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