Article ID Journal Published Year Pages File Type
3041687 Clinical Neurology and Neurosurgery 2008 7 Pages PDF
Abstract

ObjectiveTo review the direct and indirect effects on the central nervous system (CNS) of systemically administered immuno-modulatory therapies in use or under evaluation for the relapsing forms of multiple sclerosis (MS).MethodsWe summarize data published by our own lab and by others that delineate the effects of such therapies on in vitro neural cell cultures and in animal model-based systems.ResultsThe long-approved therapies, interferon β (IFNβ) and glatiramer acetate (GA), do not readily access the CNS. These agents can still indirectly have an effect on disease-related immune regulatory and effector functions within the CNS by modulating the properties of systemic immune cells that migrate to this compartment. Such immune cells could interact with perivascular and innate immune cells that are involved in immune regulation and with cells that are either targets of the disease process (oligodendrocytes, neurons) and/or are involved with repair (progenitor cells). Newer agents reported to favorably impact on relapse frequency in MS include the sphingosine-1-phosphate agonist, fingolimod, and the lipophilic statin, simvastatin. Both agents access the CNS and thus represent examples of agents that could directly impact on disease-relevant injury and repair process within the CNS.ConclusionsThe observations reviewed in this report regarding indirect and direct effects of immuno-modulatory agents on the CNS indicate the need to understand and monitor the neurobiologic effects of such therapies.

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