Epilepsy is the neurological disorder defined by spontaneous recurrent seizures, which are abnormal patterns of electrical discharge in the brain. A major advance in neurology over the last 20 years is the identification of genetic variation as an important cause of epilepsy, and in particular as a cause of the epileptic encephalopathies, defined by childhood-onset, treatment-resistant epilepsy accompanied by developmental delay leading to intellectual disability. Unfortunately, this progress in genetic diagnosis has yet to translate to effective precision or targeted therapeutics. However, in this issue of the JCI, Li and Jancovski et al. use antisense oligonucleotides (ASO) to treat or prevent epilepsy and epilepsy-associated cognitive and behavioral comorbidities in a mouse model of SCN2A encephalopathy, paralogous to the recurrent human variant SCN2A c.5645G>A (p.R1882Q) associated with epileptic encephalopathy. These findings may inform the development of targeted or personalized therapies for what is currently an incurable and largely untreatable disorder.
Ethan M. Goldberg
Antisense oligonucleotide strategies for therapeutic targeting of mRNA transcripts.