Innovative Use of Antisense Oligonucleotide Shows Promise in Treating Drug-Resistant Seizures in Preterm Infant

Researchers from Ludwig-Maximilians-Universität München have achieved a significant breakthrough in managing drug-resistant seizures in a preterm infant through the use of antisense oligonucleotide therapy. The case involved a female infant born prematurely at 29 weeks and four days who was diagnosed with early-onset SCN2A-related developmental and epileptic encephalopathy (DEE). Despite extensive treatment with multiple conventional antiseizure medications, her seizures persisted at an initial rate of 20 to 25 per hour.

The innovative treatment involved administering elsunersen, a gapmer antisense oligonucleotide designed to target SCN2A mRNA, via lumbar puncture into the cerebrospinal fluid. Prior to treatment, detailed structural modeling and electrophysiological assays confirmed increased persistent sodium current due to impaired channel inactivation caused by the SCN2A mutation.

Following the first dose, there was a marked reduction in seizure activity. Over the course of 12 weeks and multiple doses, seizure frequency decreased by approximately 67%, from nearly 20 per hour to around 6 per hour. During this period, there was no report of serious adverse events, and the treatment was well tolerated. Continuous monitoring through pharmacokinetic modeling indicated a correlation between drug levels and seizure control, suggesting that optimized dosing intervals could enhance effectiveness.

This case demonstrates that targeted antisense oligonucleotide therapy can offer substantial seizure reduction in severe genetic epilepsies where traditional treatments fail. The promising results underscore the potential of ASO technology to modulate gene expression precisely, especially for dosage-sensitive genes like SCN2A. While further research and clinical trials are necessary to establish safety and efficacy broadly, this single-patient case marks a pivotal step toward personalized genetic therapies for neonatal epileptic conditions.

Parents reported transient increases in seizure severity following doses, providing critical insights into dosage timing. Throughout the treatment, no physical or neurological complications related to the therapy were observed. By the age of 22 months, the child's seizure frequency remained stable at five to seven per hour, with ongoing treatment support.

This groundbreaking intervention highlights the importance of integrating molecular genetics and advanced therapeutic strategies to address unmet medical needs in neonatal neurology. Future studies will help determine the broader applicability of antisense oligonucleotides in treating early-onset epilepsies caused by genetic mutations.

Source: https://medicalxpress.com/news/2025-05-preterm-infant-drug-resistant-seizures.html