The multiplicity of molecularly distinct sodium channel subtypes, and their roles in the pathophysiology in MS and its models, raise the suggestion that it may be possible to therapeutically induce the expression of Nav1.2 channels so as to promote restoration of axonal conduction after demyelination, or to target sodium channels so as to retard axonal degeneration, or reduce symptoms. The ideal sodium channel blocker in this respect would be selective for the offending channel, with no side effects related to channels distributed elsewhere. Block of Nav1.6 sodium channels as a strategy for preventing axonal injury in MS might seem problematical at first sight, as these channels are distributed widely within the CNS. Studies that have already been carried out show that nonspecific sodium channel blockers can provide a degree of protection, preventing axonal degeneration and improving clinical outcome in EAE (Lo et al., 2002, 2003; Bechtold et al., 2004). Therapeutic targeting of Nav1.8 is not yet possible, as selective blockers of this channel subtype are not yet available, but the relatively selective expression of this channel within primary sensory neurons in the normal central nervous system raises the possibility that, when such blockers do become available, they may favorably impact cerebellar symptomatology without significant side effects. Thus the multiplicity of the sodium channel subtypes expressed in MS and its models, while presenting a challenge in the laboratory, may also provide multiple therapeutic opportunities.
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