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.