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 (IFNbeta) 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.


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.
Antel
Jack P
JP
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. jack.antel@mcgill.ca
Miron
Veronique E
VE
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects*; D000068876:Fingolimod Hydrochloride; D000068717:Glatiramer Acetate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D007370:Interferon Type I / Q000009:adverse effects / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy*; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D011409:Propylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins; D013110:Sphingosine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D007370:Interferon Type I; D010455:Peptides; D011409:Propylene Glycols; D011994:Recombinant Proteins; D000068717:Glatiramer Acetate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine