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Forget the bad times: potential drug for PTSD

10 Sep, 2014

It may be possible to fade memories responsible for post-traumatic stress disorder according to new research from the US and China.

In a case of life imitating art, the idea popularised in movies of a drug to wipe out bad memories may be one step closer. In a study involving mice models, the researchers from the Virginia Commonwealth University School of Medicine and the Chinese Academy of Sciences, Shanghai, were able to demonstrate “memory extinction” or the fading of fear memories by using a drug, fingolimod, used to treat a remitting-relapsing form of multiple sclerosis.

A paper advisory from the Nature Group explains that fingolimod, aka FTY720, is an oral drug made up of a small inactive molecule. Once swallowed, the drug phosphorylates or converts to its active form by an enzyme called sphingosine kinase to become FTY720-phosphate. Once active, it helps to suppress the immune system, explaining its effectiveness in treating some cases of multiple sclerosis.

However, the researchers, led by Professor Sarah Spiegel, chair of the Department of Biochemistry and Molecular Biology at VCU, found that FTY720-phosphate has another molecular function, independent of the immune system. The activated drug can cross the blood-brain barrier and also inhibit an enzyme found in the brain called histone deacetylase, a key epigenetic enzyme that regulates global gene expression. According to the team, the upshot of this inhibition was an increased expression of some genes that are important for certain memory processes. The FTY720-phosphate was acting in a similar way to a natural signalling lipid, sphingosine-1-phosphate, which it closely resembles.

In the mice models, this caused the faster extinguishing of previously acquired fear memories. Furthermore, the action was specific to the activated form of fingolimod (FTY720-phosphate), since mutant mice that lack the activating enzyme sphingosine kinase failed to show any memory changes.

In the study, mice were trained to fear a particular cage that could administer an electric shock. The mice clearly demonstrated fearful behaviour towards the cage. However, such mice could also be untrained by repeatedly putting them in the cage without any further electric shocks being administered. The researchers showed that the fearful mice who took fingolimod forgot their earlier trauma associated with the cage much more quickly than untreated mice.

The researchers suggest that, if these findings in mice are transferrable to humans, FTY720-phosphate may be used to treat post-traumatic stress disorder and other anxiety disorders related to traumatic experiences.

At present, other histone deacetylase inhibitors are used for treating various psychiatric and neurological disorders. However, according to this latest research, the way in which they work and their variable effectiveness is not fully understood. This research clarifies the pathways involved.

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