Grant round winners 2012

The immune system is our body’s means of defence against harmful substances (toxins, bacteria, viruses) that manage to enter. One of its roles is to produce antibodies, which are designed to selectively destroy disease-causing agents and limit the damage they cause. Occasionally, however, antibodies attack the body itself, leading to an ‘autoimmune’ condition, such as rheumatoid arthritis, or thyroid disease (depending upon the region affected). In many cases the number of autoimmune antibodies (autoantibodies (aabs)) can be depleted with medications such as steroids.

Focal (or partial) epilepsies (FEs) are characterised by seizures that originate in a specific part of the brain. They are relatively common forms of epilepsy, but in approximately 40% of affected adults they are idiopathic (without a known cause), and about 25% of these people do not respond to anti-epileptic drugs (AEDs): their epilepsy is said to be refractory.

In a previous project funded by Epilepsy ResearchUK, Dr Bethan Lang and colleagues, at the University of Oxford, showed that, among people with different types of epilepsy – new-onset, long-standing, severe childhood, idiopathic – many carried aabs against certain brain proteins. They also discovered that if the aabs affected the function of these proteins, they were able to help trigger the development of epilepsy. In light of these findings, the group wondered if these, and other aabs, might be the underlying cause of some cases of epilepsy that were previously thought to be idiopathic.

Dr Lang and her colleagues have now been awarded £149,916, over 3 years to carry out a project entitled ‘Established and novel cell-surface autoantibodies in adults with new-onset cryptogenic epilepsies’, in which they will investigate this theory specifically in adults with FEs.

The group will collect blood samples from adults with new-onset FE with no identified cause, and   screen them for the aabs highlighted earlier. They will also establish tests to detect new aabs, so that a more complete picture of autoimmunity in epilepsy patients can be gained. Samples will also be taken from people without epilepsy, or with generalised epilepsies, to see if any of the aabs encountered are specific toFEs and might help to diagnose/classify them.

If aabs are found to be the underlying cause of some FEs, drugs that target them can potentially be developed, and these may prove more effective in controlling seizures (in these cases) than AEDs. If successful, this could help to avoid the unnecessary long-term use of AEDs, which bring significant side-effects. Some people with refractory FE may also be given the chance of seizure freedom, without the need for more invasive treatment such as epilepsy surgery.