22 Apr 2025
A newborn baby with rare SCN2A epilepsy suffers from severe seizures. All therapies fail—until an LMU team and its partners venture a new approach. The seizures are significantly reduced. The successful treatment was published in Nature Medicine.
A child is born prematurely at LMU Hospital in Großhadern and suffers from almost constant epileptic seizures. The girl has an extremely rare condition: early-onset severe epilepsy with a sodium channel mutation, known as SCN2A-associated developmental and epileptic encephalopathy (SCN2A-DEE). All conventional seizure-interrupting therapies remain unsuccessful. Then a team from Dr. von Hauner Children's Hospital, together with the Neonatology and Pediatric Epilepsy Center at LMU Klinikum and TUM Klinikum, ventures a new treatment approach. The therapy initially leads to an interruption in the series of epileptic seizures and ultimately to a significant reduction in seizure frequency. The study has now been published in the renowned journal Nature Medicine.
Developmental disorders and epilepsy in children are often genetic in origin. SCN2A-DEE is caused by mutations in the SCN2A gene. This gene leads to the production of a special protein: a sodium channel that plays a crucial role in the function of nerve cells. Changes in this gene lead to a defective protein and impaired signal transmission in the brain. The result: very early epileptic seizures beginning before the age of three months and severe developmental disorders.
In the case of the child from Munich, the genetic defect was diagnosed while still in the womb. The value of such genetic testing has increased significantly with the advent of new precision therapies, as in the best case scenario, an innovative personalized therapy concept can be developed on the basis of a specific diagnosis. Neuropediatrics—the field that deals with neurological disorders in children and adolescents—is a pioneering discipline in this area, even though these therapies are currently only available for a few diagnoses and many scientific, technical, ethical, and care-specific questions remain unanswered.
Small RNA fragments offer hope
In the context of precision therapies, antisense oligonucleotides (ASOs) play a special role. These are small nucleic acid fragments that bind to RNA, can modulate cell biology, and are considered particularly promising for precision medicine. For example, they can inhibit the production of disease-promoting proteins. The ASO "Elsunersen" used in the new study targets the mRNA of the SCN2A gene and leads to its degradation. This prevents the production of defective proteins that cause the symptoms of the disease.
The doctors injected the girl with elsunersen directly into her spinal canal. Conventional therapy was administered at the same time. The result: a breakthrough in the permanent seizures and, over time, a reduction in seizure frequency by more than 60 percent to five to seven seizures per hour, which lasted until the age of 22 months and enabled clinical care stability. Nevertheless, serious neurological developmental disorders remained, possibly due to the long period of time the disease had been present in the womb. In terms of treatment safety, no serious side effects were observed over a period of 20 months of therapy with 19 administrations.
Precision therapies will become increasingly important in medicine
"The study highlights the potential of ASO therapies for genetic diseases," says Dr. Matias Wagner, group leader for nucleic acid therapies at the Institute of Human Genetics at TUM Klinikum and also active at LMU Klinikum during the study phase: "In the future, there will be approved drugs for precision therapies, and we will test their effectiveness in clinical trials at the center. On the other hand, there are patients for whom no such therapy option is yet available. We want to develop effective ASO therapies for these patients."
"The advent of ASO therapies has opened a new chapter in epileptology," emphasizes Prof. Ingo Borggräfe, head of the Pediatric Epilepsy Center at LMU Hospital: "Successful treatment requires extensive clinical experience, considerable personnel and logistical resources, and interdisciplinary collaboration, which will continue to shape the focus of our center now and in the years to come."
The Munich team and its cooperation partners now want to develop ASOs for other rare neuropediatric diseases, embedded in competent care structures and building on the knowledge gained and the expertise of the participating research groups within this inter-university network.
Veröffentlichung: Erstautor: Matias Wagner (TUM), Letztautor Ingo Borggräfe (LMU)
Wagner, M., Berecki, G., Fazeli, W. et al. Antisense-Oligonukleotid-Behandlung bei einem Frühgeborenen mit früh einsetzender SCN2A-Entwicklungs- und epileptischer Enzephalopathie. Nat Med (2025). DOI: https://doi.org/10.1038/s41591-025-03656-0
Participating institutions:
Funding: The study was made possible by an Expanded Access Programme from Praxis Precision Medicines. The study was also funded by a fellowship from the Hertie Network of Excellence in Clinical Neuroscience, part of the non-profit Hertie Foundation.