After several decades of development, antisense oligonucleotides (ASOs) have recently been approved as a treatment for spinal muscular atrophy and Duchenne muscular dystrophy, which demonstrated that RNA-targeted therapies are a viable therapeutic strategy for these devastating neurogenetic disorders ( 5, 6).
Several major technological advances have enabled the possibility of establishing effective targeted gene therapies for DEEs. This is especially important as the current treatments primarily focus on the symptomatic control of seizures while the developmental aspects of the disease remain untended. Identification of the genetic cause and increased understanding of the mechanistic basis of DEEs have laid the foundation for the development of precision medicine therapeutic approaches. The number of identified DEE genes is increasing, with those encoding ion channels, as the pivotal brain excitability regulators, being the most represented ( 2– 4). Only a decade ago little was known about DEE etiologies, but the employment of next-generation sequencing has identified single-gene de novo pathogenic variations as the main cause ( 2). The limited treatment options, presence of comorbidities, and the need for long-term supported care represent a burden for affected patients, caregivers, and health services. The prognosis of these patients is poor, marked by progressive disability and increased risk of early death ( 1). The affected children have ongoing, refractory seizures in addition to profound global developmental delay, intellectual disability, and movement disorders ( 1). Developmental and epileptic encephalopathies (DEEs) are devastating neurological disorders presenting during infancy and early childhood ( 1).
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