An FDA-approved multiple sclerosis drug can alter memory?

Finding ways to enhance memory has been a goal of many research labs for a very long time. It has also been a popular topic amongst science-fiction enthusiasts and college students. What would we be capable of with the ability to remember more things? Or what if we could forget unwanted memories? Oh the possibilities! Well, these types of scientific breakthroughs are no longer just a dream as researchers have now started to identify cellular mechanisms and signaling pathways that could potentially aid in altering memory. In an article published in the most recent issue of Nature Neuroscience, researchers at the University of California Irvine have shown that an FDA-approved drug for multiple sclerosis (MS) can enhance memory extinction in mice.

The MS drug, fingolimod, normally acts by binding to specific receptors on the cell membrane. This binding causes the cell to internalize the receptor, eliminating its functionality. Such a mechanism has been beneficial in the treatment of MS as the internalized receptor is necessary for the trafficking of lymphocytes, immune cells that are active in MS processes. The action of fingolimod prevents lymphocytes from leaving their home tissue, ultimately preventing them from being able to damage the nervous system.

In this study, Hait et al identifies a new role for fingolimod, one in which it acts within the nucleus of the cell as a histone deacetylase (HDAC) inhibitor, a mechanism that alters gene expression. Such a mechanism has been described as “epigenetic”, meaning that it can alter the expression of genes without affecting the actual DNA code. Epigenetic phenomena have been an important focus of many studies as it provides a means in which the environment can change your genes. Interestingly, epigenetics is believed to be involved in the development of many psychiatric disorders, disorders in which the surrounding environment plays an important role.

Other HDAC inhibitors have already been shown to alter gene expression and subsequently, memory. This might happen through varied expression of genes and proteins that are important for the formation and maintenance of memories, as it has been well established that long-term memory requires the creation of new proteins. These proteins are believed to act at specific synapses between neurons, strengthening the connections between specific cells. This study shows that fingolimod can bind to HDACs and inhibit their activity. Specifically, the authors show that this happens in neurons located in the hippocampus of the brain, a neural structure important for the formation of new memories. Perhaps the most interesting part of this study shows that mice treated with the MS drug have an enhanced ability for memory extinction as measured by the decreased amount of freezing behavior of the mice during a behavioral test.

The ability to enhance or alter memory is on its way. Drugs that can accomplish such a feat would be beneficial for the treatment of devastating neurological disorders including Alzheimer’s disease and post-traumatic stress disorder (PTSD). This new study identifies a novel pathway for changing the expression of genes involved in memory and subsequently, the enhancement of memory extinction in mice as seen in behavioral testing. Perhaps most importantly, the authors have show that this is caused by an FDA-approved drug that is already being used to treat MS, bypassing the complicated barriers presented by bringing novel drugs to market. It will be interesting to follow how HDAC inhibitors like fingolimod and other epigenetic drugs will be used in the future to better understand memory formation and maintenance, processes that have been difficult to pin down so far.

button print gry20 An FDA approved multiple sclerosis drug can alter memory?

5 Responses to An FDA-approved multiple sclerosis drug can alter memory?

  1. M Henri Day July 28, 2014 at 3:26 pm #

    Obviously no specific studies addressed to this issue have yet been performed, but I can’t help wondering if any anecdotal evidence exists with respect to how treatment with this particular drug has affected memory in MS patients….

    Henri

    • James Fink July 28, 2014 at 4:17 pm #

      Henri,

      Totally agree. In this study the mice treated with the drug were able to properly learn and perform the fear task at baseline, indicating that probably most forms of memory are not changed by this drug. The significant results were specific to the fear extinction, so when it comes to human patients being treated with the drug, it’s interesting to try and imagine real-life situations in which this type of memory can be quantified. It’s also worth wondering how and why different HDACs can alter memory in different ways. Thanks for the thought!

    • Jim Liberty July 29, 2014 at 3:16 pm #

      I have now taken Gilenya (Fingolimid) for 18 months and have not noticed any improvement in short term memory. In fact, my short term recall is worse than ever.

      • Chuck July 30, 2014 at 10:48 pm #

        Hi Jim,

        This article is talking about enhancing memory extinction in the long term by inhibiting certain proteins that may have a role in this process. This article does not necessarily talk about improving your ability to remember in the short term, but more to slow down the rates of memory loss.

        In retrospect, drugs like Fingolimod may help with other memory disorders such as Alzheimer’s disease as it may have an epiginetic effect on certain DNA sequences that are responsible for the formation of proteins associated with psychiatric disorders.

        The memory recall factors associated with MS are caused by the scar tissue formation in the cerebrum on not necessarily proteins. Treating memory problems for MS has to focus on reforming the myelin sheath in which is destroyed during the inflammatory processes of the disease.

        I hope i hoped

  2. Linda July 29, 2014 at 2:58 am #

    I read a lot of books as a child and years later developed a schzo disorder. when ill am in a state of wondering whether I experienced what was in the books.when medicated and functional still wonder whether I was there In a former life.the memories seem that real.

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