Sensitivity to light flashes used in antiepileptic drug development

Epilepsy accounts for a significant proportion of the world's disease burden. One reason is the difficulty of controlling epilepsy with the available medications. It is therefore important that novel antiepileptic drugs are being developed, providing neurologists with additional tools to improve the quality of life for epilepsy patients.

Most antiepileptic drugs work by reducing the excitability of the brain. One way to measure this is to use transcranial magnetic stimulation (TMS). CHDR's new Experimental Medicine group specialises in this. But there are also other ways. 'We were approached by a client advised by a Dutch epilepsy expert, who has a lot of experience with photosensitive epilepsy,' says Dr Philip Kremer, Research Director Neurology. 'In these patients, an epileptic seizure can be triggered by repetitive light flashes, for example a strobe or the flashes of sunlight you get when you’re in a train or a car passing a row of trees. Fortunately, a full-blown seizure is rare, but these patients regularly show a photoparoxysmal response in the EEG. This response is characterised by generalised discharges at certain frequencies of light flashes.'

The study currently being conducted by the Neurology group is based on measuring a reduction in the photoparoxysmal response. In a patient with a photosensitive form of epilepsy, the researchers determine the frequency at which a photoparoxysmal response occurs under placebo conditions. Then, at different doses of the drug, they determine whether this response decreases or even disappears. Kremer: ‘Because of the high predictability of the photoparoxysmal response, we only need a small number of patients to demonstrate an effect of the compound.’

But even finding a limited number of patients proved to be a challenge. Kremer: 'Most epilepsy patients under treatment at specialised clinics receive adequate medication, so any photosensitivity they might have had is no longer detectable. Recently, we have found a subgroup of patients we will focus our recruitment efforts on people with juvenile myoclonic epilepsy.  About one in four of these patients has a photoparoxysmal response, and some do not receive antiepileptic drugs because they do not get generalised seizures. That’s why I am hopeful that we can recruit enough participants to complete this study early in 2024.'