Treating fear with immune modulators

Memory extinction-the fading of old memories-in mice can be enhanced using a pharmaceutical drug presently used to treat a remitting-relapsing form of multiple sclerosis. The findings, reported online this week in Nature Neuroscience, suggest that this drug could be used to treat post-traumatic stress disorder and other anxiety disorders, if the same finding holds in people.

The drug, fingolimod, consists of a small molecule which is administered in an inactive form and converted in the body into an activated version by an enzyme called sphingosine kinase. Once active, it helps to suppress the immune system, thus treating some cases of multiple sclerosis.

Sarah Spiegel and colleagues report that the activated form of fingolimod has a second molecular function, independent of the immune system. The drug can inhibit an enzyme called histone deacetylase, a key epigenetic enzyme that regulates global gene expression. When administered orally to mice, fingolimod crossed the blood-brain barrier. Spiegel and colleagues report that mice given fingolimod were faster at extinguishing previously acquired fear memories. This action was specific to the activated form of the drug, since mutant mice that lack the activating enzyme sphingosine kinase failed to show memory changes.