Basic research shows that drug used to treat multiple sclerosis may have beneficial effects on memory

by Eric Peters
Demyelination by MS. The CD68 colored tissue shows several macrophages in the area of the lesion. Original scale 1:100. Credit: Marvin 101/Wikipedia

(Medical Xpress)—Virginia Commonwealth UniversitySchool of Medicine researchers have uncovered a new mechanism of action of fingolimod, a drug widely used to treat multiple sclerosis: elimination of adverse or traumatic memories.

The findings shed light on how the drug works on the molecular level – something that has not been well understood until now.

Fingolimod, or FTY720, which is the first orally available drug for treatment of , works by suppressing the immune system. Fingolimod is a prodrug that is phosphorylated in the body to its active form, FTY720-phosphate.

In a study published by the Nature Neuroscience journal on May 25 as an Advanced Online Publication, researchers used a mouse model to show that fingolimod accumulates in the brain and inhibits histone deacetylases, which are enzymes important to regulate . The team observed an increased expression of a limited number of genes important for certain memory processes. Fingolimod acted similarly to the natural signaling lipid, sphingosine-1-phosphate, which it closely resembles.

"Our work suggests that some of the beneficial effects of FTY720/fingolimod that are not well understood might be mediated by this new activity that we have discovered," said first author Sarah Spiegel, Ph.D., an internationally renowned researcher and professor and chair of the Department of Biochemistry and Molecular Biology in the VCU School of Medicine.

"It will be important in the future to determine whether this prodrug can reduce loss of cognitive functions and can erase adverse memories," she said.

Spiegel added that other have long been used for treatment of psychiatric and neurological disorders, yet the mechanism of their effectiveness is not fully understood.

"FTY720/fingolimod may be a useful adjuvant therapy to help stop aversive memories such as in and other anxiety disorders," Spiegel said.

"The work has not been extended to show effectiveness in humans at this time. We are still working to fully understand the molecular underpinnings of the drug and its link to memory," she said.

The work is based on previous findings by Spiegel's group that were published in Science in 2009. They had reported that sphingosine-1-phosphate formed in the nucleus of cells is a natural inhibitor of and a regulator of gene expression.

More information: "Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory." Nitai C Hait, et al. Nature Neuroscience (2014) DOI: 10.1038/nn.3728. Received 07 March 2014 Accepted 25 April 2014 Published online 25 May 2014

add to favorites email to friend print save as pdf

Related Stories

Researchers find MS drug erases painful memories in mice

May 26, 2014

(Medical Xpress)—A team of researchers working at Virginia Commonwealth University in the U.S. has found that giving fingolimod, a drug normally used to treat Multiple Sclerosis (MS) in people, to mice, ...

Lipid involved with gene regulation uncovered

Sep 04, 2009

Virginia Commonwealth University School of Medicine researchers have discovered a new role for the bioactive lipid messenger, sphingosine-1-phosphate, or S1P, that is abundant in our blood - a finding that could lead to a ...

Lipid involved with gene regulation uncovered

Sep 08, 2009

(PhysOrg.com) -- Virginia Commonwealth University School of Medicine researchers have discovered a new role for the bioactive lipid messenger, sphingosine-1-phosphate, or S1P, that is abundant in our blood - a finding that ...

Recommended for you

'Chatty' cells help build the brain

10 hours ago

The cerebral cortex, which controls higher processes such as perception, thought and cognition, is the most complex structure in the mammalian central nervous system. Although much is known about the intricate ...

'Trigger' for stress processes discovered in the brain

Nov 27, 2014

At the Center for Brain Research at the MedUni Vienna an important factor for stress has been identified in collaboration with the Karolinska Institutet in Stockholm (Sweden). This is the protein secretagogin ...

New research supporting stroke rehabilitation

Nov 26, 2014

Using world-leading research methods, the team of Dr David Wright and Prof Paul Holmes, working with Dr Jacqueline Williams from the Victoria University in Melbourne, studied activity in an area of the brain ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.