# Is Precision Therapy in Infantile-Onset Epileptic Encephalopathieshes Still Too Far to Call Upon?
## 3 Limitations of Phenotype-Based Therapy  
Current management strategies for EDEs rely heavily on phenotype-based antiepileptic drug (AED) selection. This \"one-size-fits-all\" approach is inadequate for genetically diverse conditions [13]. For instance, sodium channel blockers exacerbate seizures in SCN1A-related Dravet Syndrome but may be beneficial in SCN8A gain-of-function mutations. Similarly, targeted interventions such as mTOR inhibitors for TSC1/TSC2 mutations or antisense oligonucleotides (ASOs) for CDKL5 [14,15] deficiency illustrate the potential of etiology-driven therapies. However, trial-and-error methodologies often delay effective treatments, especially in conditions requiring early neurodevelopmental interventions. While precision therapies aim to overcome these limitations, they are not without their challenges. For example, pyridoxine (Vitamin B6) is considered a precision therapy for pyridoxine-dependent epilepsy (PDE), a condition caused by mutations in the ALDH7A1 gene [16]. Despite the early and timely administration of pyridoxine, nearly 75% of patients with PDE still experience intellectual disability, highlighting that metabolic supplementation alone cannot fully address the complex neurodevelopmental impairments associated with the disorder [17]. Similarly, in GLUT1 Deficiency Syndrome (GLUT1-DS), the ketogenic diet is a cornerstone of precision therapy, providing ketones as an alternative energy source for the brain [18]. However, even with strict adherence to this dietary regimen, many patients continue to experience residual neurological deficits, including learning difficulties and movement disorders [19]. These cases underscore the limitations of precision therapies in fully mitigating the effects of underlying genetic abnormalities. This reliance on phenotype-based therapy reflects a broader issue in epilepsy management: the lack of widespread integration of genetic and molecular insights into routine clinical practice [20]. Phenotypic treatments, while sometimes effective in controlling seizures, fail to address the underlying pathophysiological mechanisms of the disorder. This can lead to suboptimal outcomes, including continued developmental regression, behavioral disturbances, and worsening quality of life.  
Furthermore, the absence of robust biomarkers to predict therapeutic response complicates the timely identification of effective treatments. In many cases, patients endure multiple failed therapies before achieving seizure control. Ultimately, therapies based solely on clinical and neurological signs, such as seizure frequency, remain highly limited because they do not target the root cause of the disorder. Instead, they primarily focus on reducing seizure frequency, leaving the underlying genetic or molecular defects unaddressed. Reflecting this limitation, even the terminology in epilepsy treatment is evolving. Drugs previously referred to as antiepileptic drugs (AEDs) are increasingly being described as anti-seizure medications (ASMs) to emphasize their primary role in seizure reduction rather than addressing the broader epileptic pathology [21]. This shift underscores the urgent need for treatments that correct the fundamental pathophysiological mechanisms, enabling not only seizure control but also the prevention of long-term developmental and cognitive impairments.