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Research on the natural course of MS would include defining the relationship between cellular and molecular changes and the progression of disability, as well as determining the physiological basis for different clinical manifestations of MS. Changes in gene expression should be analyzed in individual cell types, particularly those in and at the borders of lesions. Such information will also improve the ability to develop more refined diagnostic tools, provide benchmarks against which to measure the effect of therapeutic interventions, and provide the scientific basis for new therapeutic approaches.

Research on pathological changes occurring early in the disease should be particularly emphasized. This should also include the development of improved diagnostic criteria (most likely, criteria based on neuroimaging) that allow early and more accurate diagnosis of MS. If aggressive treatment is to be instituted at the onset of disease, early and accurate diagnosis is essential.

RECOMMENDATION 2: Research should be pursued to identify how neurons are damaged in MS, how this damage can be prevented, and how oligodendrocytes and astrocytes are involved in damage and repair processes.

Specific needs for research on neurons include the following:

  • investigations into the molecular pathophysiology of axonal injury in MS—what is the response of the neuronal cell body to demyelination and to degeneration of axons in MS?

  • delineation of the relationship of axonal injury to demyelination and inflammation, to the role of cytokines, and to the role of cell and antibody-mediated immune mechanisms;

  • delineation of the detailed nature of the secondary injury cascade that underlies calcium-mediated damage of axons within white matter;

  • improved understanding of the molecular mechanisms underlying restoration of conduction in demyelinated axons, with particular attention to identification of the sodium channel subtype(s) involved in conduction in chronically demyelinated axons, and identification and characterization of the promoter regions of the sodium channels that support impulse conduction in myelinated and demyelinated axons; and

  • identification of promoters and inhibitors of axon regeneration.

Specific needs for research on oligodendroctyes include identification of:

  • the role of oligodendrocytes in the trophic support of axons and neurons;



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