Gene-targeted drug reduces seizures in children with rare form of epilepsy

A new gene-targeted drug therapy has shown promise in reducing seizures for patients with a rare genetic childhood epilepsy.

Dravet syndrome is a severe form of epilepsy in children that causes frequent, drug-resistant seizures as well as long-term developmental and cognitive problems. Current medications have been unable to effectively control this condition in most patients. However, a new experimental drug called zorevunersen has shown therapeutic potential in an international clinical trial led by researchers at University College London (UCL) and Great Ormond Street Hospital (GOSH), London. The preliminary results, published in the New England Journal of Medicine, show that zorevunersen dramatically reduced seizure frequency and was associated with improved quality of life for children with Dravet syndrome.

'This new treatment could help children with Dravet syndrome lead much healthier and happier lives,' said lead author Professor Helen Cross, head of the developmental neuroscience programme at UCL-GOSH Institute of Child Health, and honorary consultant in paediatric neurology at GOSH. 'Overall, our findings showed that zorevunersen is safe to use and well tolerated by most patients'.

Dravet syndrome is caused by a mutation in one copy of the SCN1A gene, which reduces the production of a protein critical for normal nerve cell function. This leads to over-excitable nerve cells and seizures. Zorevunersen targets this underlying mutation by boosting expression from the healthy copy of the gene, which helps to restore normal nerve activity and reduce the number of seizure episodes. Because it addresses the root cause rather than just the symptoms, the treatmentrepresents a new type of gene-targeted therapy for this condition.

The initial phase 1 and 2a clinical trials included 81 children with Dravet syndrome, aged two to 18 years, from the UK and the USA. Participants received either a single dose or multiple doses of zorevunersen over three to six months, ranging from ten to 70 mg. They were followed for two to three years to monitor safety, tolerance and clinical improvements.

Of the 81 participants in the initial trials, 75 patients have moved on to extension studies, continuing to receive the drug every four months. These studies will help determine the long-term safety and sustained effectiveness of the therapy.

So far, the results show that the drug is safe and well-tolerated, with very few severe treatment-related adverse effects. Zorevunersen was also associated with reduced seizures – patients in the extension studies who received single or multiple 70 mg doses saw reductions in seizure frequency of 59-91 percent over the course of 20 months. Participants showed overall improvements in behaviour, alertness and quality of life, with caregivers and clinicians reporting improvements in at least 84 percent of patients.

'We regularly see the devastating impact that this condition has on the lives of families. That's why we're so thrilled about these latest results from the initial zorevunersen clinical trials,' said Galia Wilson, chair of trustees at Dravet Syndrome UK. 'We're now looking forward to the phase 3 clinical trials taking place to see if the early promise we see here will translate into real hope for all those families currently affected by Dravet syndrome.'

This research highlights how targeted therapies can tackle the genetic roots of disease, offering new hope for children with rare and severe forms of epilepsy. While further studies are needed, zorevunersen represents a significant step toward precision medicine for neurodevelopmental disorders.