# Is Precision Therapy in Infantile-Onset Epileptic Encephalopathieshes Still Too Far to Call Upon?
## 5 Barriers to Implementation  
Despite the transformative potential of precision therapy to revolutionize the treatment landscape for epileptic and developmental encephalopathies (EDEs), several critical barriers impede its widespread implementation. Addressing these obstacles is essential to unlock the full promise of precision medicine and ensure equitable access to these life-changing interventions:  
1. Diagnostic Delays: In pediatric patients, the lack of access to advanced genetic testing can prolong the diagnostic odyssey, delaying effective interventions during critical neurodevelopmental periods. For example, in a child presenting with early-onset seizures, timely identification of a pathogenic SCN1A mutation could prevent inappropriate treatment with sodium channel blockers, which may exacerbate symptoms. Similarly, delays in identifying ALDH/A1 mutations in Pyridoxine-Dependent Epilepsy (PDE) or SLC2A1 mutations in GLUT1-Deficiency Syndrome (GLUT1-DS) can postpone the initiation of targeted therapies such as pyridoxine supplementation or the ketogenic diet, respectively. These delays not only exacerbate seizure activity but also contribute to long-term neurodevelopmental impairments [29]. 2. Therapeutic Accessibility: The financial burden and regulatory complexities surrounding novel therapies pose significant barriers. For instance, treatments like antisense oligonucleotides (ASOs) for CDKL5 deficiency or gene-specific therapies for rare epilepsies often remain prohibitively expensive, limiting availability to families with sufficient financial resources [30]. Even less costly interventions, such as the ketogenic diet for GLUT1-DS, can be challenging to implement due to the need for specialized dietary planning and ongoing monitoring. Similarly, while pyridoxine therapy for PDE is more accessible, its effectiveness is limited by the availability of specialists who can diagnose and monitor these patients effectively. The complexity of personalized treatments often requires advanced technologies, extensive testing, and ongoing monitoring, all of which contribute to elevated costs. Additionally, regulatory hurdles can slow the introduction innovative therapies to clinical practice. To address these challenges, healthcare systems could explore innovative solutions such as public-private partnerships to share costs, adopt more flexible regulatory pathways for faster approval, and implement reimbursement models that prioritize value over volume. International collaboration between researchers, rulers, and the private sector will be essential to overcoming these barriers and making precision therapies more accessible. 3. Clinical Evidence: The scarcity of randomized controlled trials (RCTs) for rare genetic epilepsies limits evidence-based treatment options [31]. Diseases like West Syndrome, Dravet Syndrome, PDE, and GLUT1-DS often rely on small-scale studies or case reports, which hinder the development of standardized therapeutic guidelines. For instance, while the ketogenic diet is widely recognized as a cornerstone therapy for GLUT1-DS, its long-term impact on cognitive outcomes and quality of life remains incompletely understood. Similarly, although pyridoxine supplementation for PDE is effective in reducing seizures, its role in preventing neurodevelopmental delay requires further investigation. 4. Healthcare Education: Knowledge gaps in genomic medicine impede clinical integration. A pediatrician encountering a child with developmental delays and refractory seizures may lack sufficient training to interpret genetic testing results or recognize gene-specific treatment opportunities [32]. For example, clinicians unfamiliar with the metabolic basis of GLUT1-DS might not consider the ketogenic diet as a therapeutic option, or they might fail to promptly initiate pyridoxine therapy in suspected PDE cases. Comprehensive training programs in genomic medicine, integrated into pediatric neurology curricula, are essential to bridge these gaps.