21 November 2012 Last updated at 14:02 GMT
'Fat' drug could treat epilepsy
A substance made by the body when it uses fat as fuel could provide a new way of treating epilepsy, experts hope.
Researchers in London who have been carrying out preliminary tests of the fatty acid treatment, report their findings in Neuropharmacology journal.
They came up with the idea because of a special diet used by some children with severe, drug resistant epilepsy to help manage their condition.
The ketogenic diet is high in fat and low in carbohydrate.
The high fat, low carbohydrate diet is thought to mimic aspects of starvation by forcing the body to burn fats rather than carbohydrates.
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The identification of these fatty acids is an exciting breakthrough”
Although often effective, the diet has attracted criticism, as side-effects can be significant and potentially lead to constipation, hypoglycaemia, retarded growth and bone fractures.
By pinpointing fatty acids in the ketogenic diet that are effective in controlling epilepsy, researchers hope they can develop a pill for children and adults that could provide similar epilepsy control without the side-effects.
In early trials, the scientists, from Royal Holloway and University College London, say they have identified fatty acids that look like good candidates for the job.
They found that not only did some of the fatty acids outperform a regular epilepsy medication called valproate in controlling seizures in animals, they also had fewer side-effects.
Epilepsy is a condition in which disturbances to the brain's normal electrical activity result in seizures, sometimes known as fits
Seizures vary in severity from a few seconds of trance-like state to loss of consciousness and convulsions - uncontrollable jerking of the body
The condition is thought to affect about 500,000 people in the UK - roughly one in every 100
Triggers for seizures include flashing lights (such as strobe effects), excessive alcohol, lack of sleep and stress
Medication cannot cure epilepsy but anti-epileptic drugs (AEDs) are used to control seizures. These are effective in about 70% of cases
Source: BBC Health
But many more tests are needed to determine if the treatment would be safe and effective in humans.
Prof Matthew Walker, from the Institute of Neurology, University College London, said: "Epilepsy affects over 50 million people worldwide and approximately a third of these people have epilepsy that is not adequately controlled by our present treatments.
"This discovery offers a whole new approach to the treatment of drug-resistant epilepsies in children and adults."
Simon Wigglesworth, deputy chief executive at Epilepsy Action, said: "We know the ketogenic diet can be a highly effective treatment for children with difficult to control epilepsy and it is starting to be used for adults.
"The diet is high in fats and low in carbohydrates and the balance of the diet needs to be carefully worked out for each child. Although some children manage the diet very well, others find the diet unpleasant and difficult to follow. Children can also experience side-effects including constipation and weight loss.
"The identification of these fatty acids is an exciting breakthrough. The research means that children and adults with epilepsy could potentially benefit from the science behind the ketogenic diet without dramatically altering their eating habits or experiencing unpleasant side-effects.
"We look forward to seeing how this research progresses."
Seizure control by ketogenic diet-associated medium chain fatty acids
Pishan Changa, Nicole Terbacha, Nick Plantb, Philip E. Chena, Matthew C. Walkerc, , , Robin S.B. Williamsa, ,
a Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham, TW20 0EX, UK
b Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK
c Department of Clinical and Experimental Epilepsy, Institute of Neurology, University of London, WC1N 3BG, UK
http://dx.doi.org/10.1016/j.neuropharm.2012.11.004, How to Cite or Link Using DOI
The medium chain triglyceride (MCT) ketogenic diet is used extensively for treating refractory childhood epilepsy. This diet increases the plasma levels of medium straight chain fatty acids. A role for these and related fatty acids in seizure control has not been established. We compared the potency of an established epilepsy treatment, Valproate (VPA), with a range of MCT diet-associated fatty acids (and related branched compounds), using in vitro seizure and in vivo epilepsy models, and assessed side effect potential in vitro for one aspect of teratogenicity, for liver toxicology and in vivo for sedation, and for a neuroprotective effect. We identify specific medium chain fatty acids (both prescribed in the MCT diet, and related compounds branched on the fourth carbon) provide significantly enhanced in vitro seizure control compared to VPA. The activity of these compounds on seizure control is independent of histone deacetylase inhibitory activity (associated with the teratogenicity of VPA), and does not correlate with liver cell toxicity. In vivo, these compounds were more potent in epilepsy control (perforant pathway stimulation induced status epilepticus), showed less sedation and enhanced neuroprotection compared to VPA. Our data therefore implicates medium chain fatty acids in the mechanism of the MCT ketogenic diet, and highlights a related new family of compounds that are more potent than VPA in seizure control with a reduced potential for side effects.
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