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New Epilepsy Drug From Fatty Acids

Scientists in London have identified specific fatty acids that could form the basis of new drugs to treat epilepsy in children and adults. They suggest drugs based on them could provide similar epilepsy control as a ketogenic diet, a treatment often prescribed for children with severe drug-resistant epilepsy and which mimics aspects of starvation but with troubling side effects.

By pinpointing exactly which fatty acids in the ketogenic diet are effective in controlling seizures, the researchers, from University College London (UCL) and Royal Holloway, hope they will lead to new anti-epileptic treatments that offer the benefit of the diet without its side effects.

An early "in press" report of their work was published online in the journal Neuropharmacology on 20 November.

Professor Matthew Walker, of UCL's Institute of Neurology, speaks about the value of their findings in a press statement:

"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." Ketogenic Diet Has Significant Side Effects Children with severe drug-resistant epilepsy are often prescribed the ketogenic diet, a high fat, low carbohydrate diet that is thought to simulate starvation by forcing the body to burn fats rather than carbs.

The diet often works but draws criticism because it can lead to significant side effects such as constipation, low blood sugar (hypoglycaemia), growth retardation and bone fractures.

While it is not clear exactly how the ketogenic diet works, scientists suggest it could be because it raises blood levels of medium straight chain fatty acids. Specific Fatty Acids Potentially More Potent and Less Harmful In their study, Walker and colleagues compared the potency of an established antiepileptic drug, Valproate (VPA), with a range of diet-associated medium straight chain fatty acids ("and related branched compounds").

They found not only were some of the fatty acids better at controlling seizures than the established treatment, they also had fewer side effects.

"Our data therefore implicates medium chain fatty acids in the mechanism of the MCT [medium chain triglyceride] 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," they conclude.

Professor Robin Williams, of Royal Holloway's Centre of Biomedical Sciences, describes the work as an "important breakthrough":

"The family of medium chain fatty acids that we have identified provide an exciting new field of research with the potential of identifying, stronger, and safer epilepsy treatments," he adds.

However, there is still a long way to go, and many more rounds of tests to do, to find out if a treatment based on these fatty acids works safely in humans.

Patents are being pursued for the specific fatty acids in this study, and Royal Holloway is looking for commercial organizations to team up with to look at the potential for developing new drugs based on them. Reducing Use of Animals in Research Another noteworthy aspect of the study is that it builds on work funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), where most of the animal testing for developing anti-epilepsy drugs is being replaced by a method that uses a simple amoeba to initially screen and identify improved treatments, as Williams explains:

"Animals are often used in the search for new epilepsy treatments. Our work provides a new approach, helping us to reduce reliance on animals and provide potential major improvements in human health."

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