Spotless mind: Epigenetic drug wipes clean fear memories

Researchers have identified a class of drug that helps clear traumatic memories in mice. The drug may help
improve the effectiveness of behavioural therapy in the treatment of post-traumatic stress disorder (PTSD).

In the study, scientists from the Massachusetts Institute of Technology simulated PTSD in mice by conditioning them to associate a loud noise with the
pain of a mild shock to the feet, causing them to freeze whenever they
heard it. Mice were then subject to behavioural therapy where a loud
noise was played but no shock was administered.

The researchers found that treating
the mice with a class of drugs called HDAC (histone deacetylase) inhibitors in
combination with the behavioural therapy helped the mice forget the traumatic
association between the noise and pain. This worked whether the traumatic
memory was 30 days old or had been acquired the previous day. When mice were
treated with behavioural therapy alone, only the recently-acquired bad memories
were cleared.

Study lead author Professor Li-Huei Tsai said that: 'By
inhibiting HDAC2 activity we can drive dramatic structural changes in the
brain. What happens is the brain becomes more plastic, more capable of forming
very strong new memories that will override the old fearful memories'.

HDAC inhibitors work by
modifying so-called epigenetic markers on a DNA sequence. These markers do not
alter the DNA itself but change the way in which particular genes are
expressed. When traumatic experiences occur, epigenetic changes take place over
time, allowing bad memories to become engrained and meaning that older
traumatic memories are harder to clear. In this study, treatment with HDAC inhibitors
alters the epigenetic marks on genes involved in memory formation, thereby switching
on the process that allows old traumatic memories to be overwritten and new
memories to form.

PTSD is a condition that
affects one in three people who experience a traumatic incident such as a
military combat or a serious road accident. Patients are often treated with
behavioural therapy but this is less likely to work when the traumatic event
occurred many years before. HDAC inhibitors may be particularly useful in
treating these well-established traumatic memories.

Some HDAC inhibitors are
already licensed as cancer medicines but Professor Tsai
believes that these drugs could one day be used in the treatment of PTSD.

'I hope this will convince
people to seriously think about taking this into clinical trial and seeing how
well it works', she says.

The study was published in
the journal Cell.