Drug which can stop post-traumatic stress disorder could be on the way after successful test in miceResearchers prevent learning and memory problems in mice after subjecting them to stressClinical trials of new drug could begin in a few years
20:29 GMT, 30 August 2012
Hope on the horizon: Scientists believe they may be able to combat post-traumatic stress disorder, a condition that often afflicts war veterans
A drug could be developed to treat war veterans and others suffering from post-traumatic stress disorder, it was revealed today.
Using an experimental substance on mice, researchers have been able to prevent learning and memory problems which are symptoms of stress-related illnesses.
PTSD is a disabling anxiety disorder
triggered by a traumatic experience, ranging from a one-time event, such as being assaulted, to chronic stresses, such as those experienced
Patients are commonly treated with
supportive therapies, including antipsychotics, antidepressants,
anti-anxiety medications, and psychotherapy.
However, there is currently
no specific treatment for PTSD and related disorders.
Study leader Doctor Andrew Marks, chair and professor of physiology and cellular biophysics at Columbia University Medical Centre (CUMC) in the United States, said: 'With the dramatic rise in cases of PTSD among our combat veterans, and following common afflictions such as heart attacks, there is a pressing need for new and better therapies for this debilitating disorder.
'Our study provides new insight regarding the mechanism of stress-related cognitive disorders, as well as a potential treatment based on the understanding of this mechanism.'
Several studies have shown that chronic stress could affect the structure and function of neurons in the hippocampus, part of the brain which plays a central role in learning and memory.
Now Dr Marks believes stress may cause PTSD by destabilising type 2 ryanodine receptors (RyR2) channels in the hippocampus, which regulate calcium levels in neurons vital to cell survival and function.
In earlier mouse studies, Dr Marks and his team showed that stress can cause heart muscles to leak calcium resulting in heart failure and arrhythmias.
To find out if calcium levels are a factor in stress-related cognitive disorders, the researchers subjected mice to stressful conditions for three weeks.
Breakthrough: Researchers managed to prevent memory and learning problems in mice using an experimental drug after subjecting them to stressful conditions (file picture)
This raises their corticosteroid levels, a classic marker of stress, and activates genes known to be expressed in response to stress.
Dr Marks said: 'When we examined the hippocampal neurons of the stressed mice, we found that their RyR2 channels had become destabilized and leaky compared with channels from normal non-stressed mice which were not leaky.
'There was a remodelling of the channels that we had previously seen in heart and skeletal muscles from animal models of chronic diseases including heart failure and muscular dystrophy.
'We found these same leaky channels in samples from patients with these disorders but not in those from healthy humans.'
He added: 'The next question was ‘do the leaky channels affect memory and learning, two functions that are impaired in individuals with PTSD’
'Using classic behavioural and cognitive function tests, including a water-maze and object-recognition tests, we found that the stressed mice developed profound cognitive abnormalities affecting both learning and memory.'
The researchers confirmed that hippocampal RyR2 channels were involved in the cognitive decline of the mice in two ways.
First, when the mice were given Rycal S107, a novel drug designed in Dr Marks’ lab that prevents the calcium leak by stabilizing RyR2 channels, cognitive function was not affected by exposure to chronic stress.
Secondly, the researchers created a strain of mice in which stress signals cannot destabilize hippocampal RyR2 channels. When these mice were subjected to chronic stress, they showed no signs of cognitive impairment.
Dr Marks expects that clinical trials with S107, or a similar Rycal, for the treatment of PTSD could begin within several years. Another Rycal is currently being tested in patients with heart failure and arrhythmias.
The researchers are also examining the role of these RyR2 channels in neurodegenerative diseases, including Alzheimer’s.
The findings were published in the online edition of the journal Cell.