Despite the arrival on the market of about ten new anti-epileptic drugs in the last two decades, the proportion of people with epilepsy who cannot achieve seizure control with medication has remained about the same, 30%. Why is this? The answer might lie in their genes.

With the development of genetic research into epilepsy, one of the fields opening up is pharmacogenomics, or how our genes affect how we respond to drugs. This research aims to develop ways to identify in advance whether a person will respond to a particular anti-epileptic drug (AED) or not, or whether they will experience serious adverse effects to a drug. Drugs that are anticipated not to work in a person or to cause unacceptable levels of side effects could then be avoided.

Previous studies suggested that a gene called RLIP76 might be involved in determining whether a person responds to an AED or not. The RLIP76 gene codes for a protein which transports drug molecules into cells in the brain. A change in this protein would affect response to all AEDs. However, since carbamazepine is thought to interact with this protein directly, response to carbamazepine would depend more strongly on variation in the RLIP76 gene.

Researchers at Imperial College London led by Dr Guy Leschziner investigated whether any of the 23 common variations in this gene were associated with response to treatment with an AED. They looked at a group of 503 people with epilepsy being treated with one of 13 different AEDs in the SANAD study, the largest epilepsy treatment
trial ever carried out. The researchers focused on four different measures of efficacy for an AED: time to first seizure, time to 12 months' seizure freedom, time to withdrawal from the study due to inadequate seizure control, and time to withdrawal due to unacceptable side effects of the medication.

The researchers found that no variant in the RLIP76 gene was consistently associated with response to treatment with all drugs in the study. It therefore looks like the RLIP76 gene doesn't affect treatment response to AEDs. However, two variants of RLIP76 did appear to affect time to first seizure for patients on carbamazepine, though they did not affect the other three measures of efficacy. It would be worth investigating this link in more detail. This study was published in the journal Pharmacogenomics in December 2007.

Though this is a negative result, it is a useful one, as it still increases what's known about epilepsy and how AEDs work.