Central nervous system effects of current and emerging multiple sclerosis-directed immuno-therapies

Objective: To 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). Methods: We 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. Results: The long-approved therapies, interferon beta (IFN beta) 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 reagulation and with cells that are either targets of the disease process (oligodendrocytes, neurons) and/or arc involved with repair (progenitor cells). Newer agents reported to favorably impact on relapse frequency in MS include the sphingosine-I-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. Conclusions: The 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. (C) 2008 Published by Elsevier B.V.