New hope for treating neonatal seizures

Trials of an anti-seizure drug in newborns are showing great promise, giving researchers hope for treating neonatal seizures and preventing their devastating consequences.

Dr Tamara Yawno, from Hudson Institute’s Ritchie Centre and Monash University’s Department of Paediatrics and Department of Obstetrics and Gynaecology, published her latest findings in the journal Annals of Neurology.

Here she answers key questions about her research, focussing on a trial of the anti-seizure drug ganaxolone for treating neonatal seizures.

What percentage of babies have seizures?

Around 10 per cent of newborn babies in Australia are diagnosed with seizures each year. Seizures worsen neurodevelopmental outcomes following hypoxic brain injury. Despite evidence of the limited effectiveness and potential neurotoxicity of current anti-seizure medication, treatment of neonatal seizures has not changed for many decades.

What longer-term problems can these seizures cause?

Seizures in neonates, babies less than four weeks old, are relatively common and are strong predictors of long-term cognitive and developmental impairment like cerebral palsy. Current anti-seizure therapies like phenobarbitone have been shown to cause brain injury as they have the potential to be neurotoxic.

What is new about your study?

This study provides clinicians with evidence for the most efficacious treatment to use in neonates suffering seizures, and a treatment that is also neuroprotective for the neonatal brain.

Is it a world-first?

This is a world first study that shows an agent used to treat neonatal seizures is also used to protect the brain from further injury, and this issue has never been addressed.

Is this an existing medication and if so what is it already approved for?

Ganaxolone is approved for the treatment of epilepsy in adults and the paediatric population, but has never been used for the treatment of neonatal seizures.

How much more effective was ganaxolone than what has been used previously?

Ganaxolone treatment was associated with an 86.4 per cent reduction in the number of seizures compared to the untreated group. The total seizure duration was shorter in those with asphyxia that had ganaxolone, than those with untreated asphyxia. Ganaxolone treatment, but not phenobarbital, reduced neuronal degeneration neuroinflammation within the brain.

How likely is it to work in humans?

We believe our preclinical model addresses the issues that the neonates face in the clinic but providing evidence that ganaxolone can effectively reduce the number and duration of seizures and protect the brain from injury is strong evidence that ganaxolone will help newborn babies.

How confident are you that this drug will improve the lives of babies living with seizures?

A dilemma facing clinicians is that, at the present time, we do not have effective anti-seizure agents for newborn infants. Current neonatal seizure treatments such as phenobarbital are simply less effective in newborns than adults and are effective in eliminating the physical convulsions caused by seizures, but not the electrical discharge within the cortex, thus they do not effectively treat full seizure burden. Finally, there is significant concern that phenobarbitone can itself cause brain injury. Here, we provide evidence that ganaxolone will not only reduce seizure burden but will protect the developing brain from further injury, which gives us full confidence that the treatment will be effective.

How far off are human trials?

We are now working with the company that makes ganaxolone for clinical use, in the hope that within the next two–three years, we will be able to begin our clinical trials.

If this drug works on humans, what potential does it have to prevent/treat seizures? And would that be all types of seizures or just some of them?

Results from this work will not only reduce the incidence of neonatal seizures but also aims to reduce lifelong disabilities that are associated with seizures in the neonatal period.