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Perspective

Is Precision Therapy in Infantile-Onset Epileptic Encephalopathies Still Too Far to Call Upon?

by
Raffaele Falsaperla
1,
Vincenzo Sortino
2 and
Piero Pavone
3,*
1
Department of Medical Science-Pediatrics, University of Ferrara, 44124 Ferrara, Italy
2
Unit of Clinical Pediatrics, AOU “Policlinico-San Marco”, PO "San Marco", University of Catania, 95123 Catania, Italy
3
Unit of Clinical Pediatrics, AOU “Policlinico”, PO “G. Rodolico”, University of Catania, 95123 Catania, Italy
*
Author to whom correspondence should be addressed.
Appl. Sci. 2025, 15(5), 2372; https://doi.org/10.3390/app15052372 (registering DOI)
Submission received: 6 February 2025 / Revised: 20 February 2025 / Accepted: 21 February 2025 / Published: 23 February 2025
(This article belongs to the Special Issue Brain Functional Connectivity: Prediction, Dynamics, and Modeling)
Review Reports Versions Notes

Abstract

:

Featured Application

This research highlights the application of precision medicine in treating epileptic and developmental encephalopathies (EDEs) through early genetic diagnostics and tailored therapies. By enabling gene-specific treatments, this approach offers the potential to improve outcomes and prevent neurodevelopmental impairments in affected patients.

Abstract

Epileptic and developmental encephalopathies (EDEs) are a group of severe, genetically various neurological conditions characterized by early-onset seizures and developmental impairments. Recent advances in molecular genetics and diagnostic tools have led to the development of precision therapies, aiming to address the deep causes of these disorders. Examples, such as pyridoxine for pyridoxine-dependent epilepsy and the ketogenic diet for GLUT1 deficiency syndrome illustrate the potential of presumed tailored treatments. However, challenges persist, as current therapies often fail to fully mitigate neurodevelopmental impairments. Moreover, traditional phenotype-based management strategies, while effective for seizure control, do not address the root causes of these disorders, underscoring the limitations of existing approaches. This article explores the evolving landscape of precision medicine in EDEs, emphasizing the importance of genetic insights in therapy design and the need for a multidisciplinary approach. It also highlights the barriers to widespread implementation, including diagnostic delays, accessibility, and a lack of robust clinical evidence. To fully realize the potential of precision therapies, comprehensive genetic integration, innovation in treatment, and global collaboration are essential. The future of EDE management lies in therapies that not only control symptoms but also correct genetic and molecular defects, offering a more effective, individualized approach to care.

1. Introduction

Epileptic and developmental encephalopathies (EDEs) are severe neurological disorders marked by early-onset seizures, developmental delays, and cognitive and motor impairments [1]. These disorders, predominantly manifesting in infancy or early childhood, involve multisystemic complications including psychiatric, behavioral, sleep, gastrointestinal, musculoskeletal, and movement disorders [2]. Despite phenotypic similarities, EDEs are genetically heterogeneous, encompassing syndromes such as Early Myoclonic Encephalopathy, Ohtahara Syndrome, West Syndrome, and Dravet Syndrome [3]. Recent advancements in molecular genetics, neurodiagnostic technologies including functional study such as molecular dynamics and patch clamps have refined our understanding of these disorders.
Precision therapies have emerged as targeted approaches to address the root causes of specific EDEs, marking a pivotal shift from conventional treatments. For example, pyridoxine (Vitamin B6) is an effective treatment for pyridoxine-dependent epilepsy, a rare autosomal recessive disorder caused by mutations in the ALDH7A1 gene. Early administration of pyridoxine not only prevents seizures but also mitigates long-term neurodevelopmental damage [4]. Similarly, the ketogenic diet, a high-fat, low-carbohydrate dietary regimen, serves as a precision therapy for GLUT1 Deficiency Syndrome (GLUT1-DS) by providing ketones as an alternative energy source for the brain [5]. This diet has demonstrated remarkable efficacy in reducing seizure frequency and improving cognitive function, offering a tailored solution that directly targets the metabolic dysfunction underlying the condition.
However, it is important to note that not all therapies classified as “precision” share the same degree of specificity or mechanistic insight [6]. While the ketogenic diet directly addresses the metabolic needs of GLUT1-DS patients by bypassing the impaired glucose transport system, it remains a broader intervention compared to gene-specific therapies, such as antisense oligonucleotides or CRISPR-based approaches targeting specific mutations [7]. Similarly, pyridoxine therapy, while life-changing for individuals with pyridoxine-dependent epilepsy, relies on metabolic supplementation rather than directly correcting the genetic mutation itself [8]. These examples illustrate that precision therapies can vary significantly in their level of refinement, ranging from metabolic interventions to advanced gene editing technologies.
The aim of this perspective articles lies in its comprehensive exploration of the current state of precision therapy for EDEs, bridging the gap between emerging research and clinical application. By highlighting the potential and challenges of precision medicine, this work serves as a valuable resource for clinicians, researchers, and policymakers aiming to improve outcomes for individuals with these complex disorders. Moreover, it underscores the need for multidisciplinary collaboration and innovation to expand the scope of precision therapies, ensuring that advances in molecular and genetic science translate into tangible benefits for patients. This article not only emphasizes the transformative potential of precision medicine but also advocates for its integration into routine clinical practice, paving the way for a more tailored and effective approach to managing EDEs.

2. Advances in Diagnostic Approaches

The diagnostic landscape of EDEs has transformed with tools such as next-generation sequencing (NGS), whole-exome sequencing (WES), and whole-genome sequencing (WGS). These technologies have identified over 900 monogenic causes of EDEs, including mutations in SCN1A, KCNQ2, and CDKL5 [9]. Complementary functional assays and neuroimaging techniques, such as MRI spectroscopy and functional connectivity analyses, enable detailed correlations between genetic and brain abnormalities [10]. Integration of biomarkers, such as CSF neurofilament light chain levels and EEG patterns, further enhances diagnostic precision [10].
Advanced functional methods have further revolutionized the understanding of genetic mutations in EDEs. For instance, the patch-clamp technique is a powerful electrophysiological method that allows for the analysis of ion channel mutations by assessing their functional properties. This method has been particularly impactful in characterizing gain-of-function or loss-of-function mutations in genes such as SCN1A and SCN2A, which encode sodium channels critical for neuronal excitability [11]. By elucidating the precise effects of mutations on channel behavior, patch-clamp studies provide essential data for tailoring specific therapeutic strategies.
Additionally, molecular dynamics simulations have emerged as a crucial tool for investigating the interaction between mutated proteins and potential therapeutic compounds. This computational approach models the structural and dynamic behavior of proteins at an atomic level, enabling researchers to predict how specific drugs bind to and modulate the activity of mutated targets. For example, in GNAO encephalopathy, a rare condition caused by pathogenic variants in the GNAO1 gene, molecular dynamics has been employed to analyze how mutations in the Gαo protein affect its interaction with guanosine triphosphate (GTP) and downstream signaling pathways [12]. In this article Falsaperla et al. [12] showed that the molecular dynamics approach was pivotal in identifying tetrabenazine as a candidate drug capable of modulating the dysfunctional Gαo protein and mitigating movement disorders and seizures associated with the condition. This discovery highlights the potential of combining computational insights with clinical pharmacology to develop targeted treatments for rare genetic disorders.
Despite these advancements, conventional antiepileptic drug (AED) treatments remain seizure-focused and disregard specific genetic pathophysiologies. This limitation often leads to delayed interventions, continued developmental regression, and suboptimal patient outcomes. The integration of functional assays, such as patch-clamp and molecular dynamics, into diagnostic workflows holds the potential to bridge this gap, facilitating more accurate diagnoses and personalized treatments.

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.

4. Precision Therapy: A Paradigm Shift

Precision therapy aims to tailor medical interventions to the unique genetic and molecular characteristics of epileptic and developmental encephalopathies (EDEs) [22]. This strategy offers a transformative approach, moving beyond conventional seizure control to directly address the underlying causes of these disorders. The implementation of precision therapy leverages a variety of innovative mechanisms and approaches, including:
  • Gene-Specific Targeting: Approaches such as sodium channel modulators for SCN2A mutations, antisense oligonucleotides (ASOs) for Angelman Syndrome, and CRISPR-based gene editing for mutation correction exemplify how genetic insights can directly inform therapeutic strategies [23].
  • Pathway-Specific Interventions: Examples include mTOR inhibitors for tuberous sclerosis complex (TSC) [24], AMPA receptor modulators for GRIN2A-related encephalopathies [25]. These interventions target disrupted molecular pathways to restore cellular function. Additionally, pyridoxine (Vitamin B6) is a cornerstone therapy for pyridoxine-dependent epilepsy (PDE), effectively reducing seizures by addressing the metabolic defect caused by ALDH7A1 mutations. Similarly, the ketogenic diet, a high-fat, low-carbohydrate regimen, is a precision therapy for GLUT1 Deficiency Syndrome (GLUT1-DS), providing an alternative energy source (ketones) for the brain and mitigating seizures caused by impaired glucose transport.
  • Early Diagnosis and Intervention: Early identification of genetic mutations through newborn screening programs facilitates the timely initiation of treatments during critical neurodevelopmental periods, potentially mitigating irreversible damage. For instance, recognizing ALDH7A1 mutations in PDE [26] or SLC2A1 mutations in GLUT1-DS allows for the immediate application of therapies like pyridoxine or the ketogenic diet, which are most effective when initiated early.
  • Biomarker-Driven Outcomes: Biomarkers, such as CSF neurofilament light chain levels and EEG patterns, enable real-time monitoring of disease progression and treatment efficacy, providing valuable feedback for optimizing interventions [27].
  • Multidisciplinary Care: Precision therapy necessitates collaboration among geneticists, neurologists, metabolic specialists, and dieticians to develop and implement comprehensive care plans that address both the genetic and metabolic needs of patients [28].
Although these advancements represent a paradigm shift, significant challenges remain in implementing precision therapy on a broader scale. The cost of gene-specific treatments, limited availability of advanced diagnostic tools, and the need for robust clinical evidence to validate emerging therapies hinder their widespread adoption. Moreover, even precision therapies like pyridoxine for PDE or the ketogenic diet for GLUT1-DS, while impactful, do not fully mitigate the neurological and developmental challenges posed by these conditions, highlighting the need for ongoing innovation and refinement.

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:
  • 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 ALDH7A1 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].
  • 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.
  • 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.
  • 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. These programs should include case-based learning and real-world applications to equip clinicians with the tools to personalize care effectively. The following table, Table 1, provides a concise summary of key aspects discussed in this paper, highlighting the tools, interventions, and strategies integral to advancing precision therapy in pediatric epileptic and developmental encephalopathies (EDEs).

6. The Path Forward

To fully harness the transformative potential of precision therapy, a multifaceted approach is necessary. Addressing current barriers requires a comprehensive framework that integrates genetic insights into clinical workflows, drives innovation in treatment modalities, and fosters collaboration across global networks. These strategies must be complemented by robust educational initiatives and patient-centered approaches to ensure meaningful and equitable implementation. The key elements include:
  • Integration of Genetic Testing: Establishing genetic testing as a diagnostic standard is particularly critical in pediatric care. For example, identifying a pathogenic KCNQ2 mutation in an infant presenting with neonatal seizures can facilitate targeted treatment strategies, such as the use of sodium channel modulators, significantly improving developmental outcomes and reducing seizure burden [33]. Early genetic insights also help avoid ineffective or harmful therapies, enabling a precision-guided approach from the outset of care.
  • Studies on the impact of commonly used anti-epileptic drugs on gene expression: There are a few studies in the Literature on the impact of commonly used anti-epileptic drugs on the expression of genes linked to epiepileptogenesis. For example, in human embryonic stem cell based targeted to neural differentiation, valproic acid and carbamazepine exposure during differentiation determinate concentration-dependent reduced expression of βIII-tubulin, Neurogin1 and Reelin. Valproate caused an increased gene expression of Map2 and Mapt which is possibly related to the neural protective effect [34]. Of interest, Levetiracetam, one of the most widely used and safest anti-epileptic drugs, seems modular, in mice model, epileptogenesis by acting on the adenosine pathway with an increasing gene expression of A1Rs and Kir3.2 in the brain and a reduction in the gene expression of ENT1 central nervous system [35]. Over the past two decades, drug repositioning strategies have become increasingly significant due to their lower failure rates and reduced economic costs. Drugs with comparable side effect profiles may act through a shared mechanism, allowing them to be applied to the treatment of other diseases [36]. This knowledge is particularly important for countries with limited resources where ‘old’ drugs can be used for ‘new’ therapeutic targets, representing a variety of precision medicine.
  • Therapeutic Innovation: Expanding pipelines for gene-specific therapies is particularly impactful in pediatric care. For example, in the context of epileptic disorders, therapies targeting SCN1A mutations in Dravet Syndrome have shown transformative potential [37]. Precision treatments such as fenfluramine have demonstrated efficacy in significantly reducing seizure frequency and improving quality of life in affected children [38]. These innovations underscore the critical role of tailoring interventions to the genetic basis of pediatric epileptic conditions, fostering both better seizure management and enhanced developmental outcomes.
  • Global Collaboration: Enhancing data sharing and standardizing guidelines is vital in addressing rare pediatric epileptic disorders. For example, global initiatives like the International League Against Epilepsy’s (ILAE) collaborative networks enable clinicians and researchers worldwide to pool genetic data, share clinical insights, and standardize treatment protocols [39]. This collective approach ensures that even children in resource-limited settings can benefit from the latest advancements in precision therapies, improving diagnostic and therapeutic outcomes across diverse healthcare systems.
  • Education and Advocacy: Empowering healthcare providers and patients through education is critical for the effective implementation of precision medicine [40]. For instance, in pediatric epilepsy, equipping clinicians with genomic knowledge allows them to recognize actionable mutations such as SCN1A in Dravet Syndrome, enabling timely and appropriate treatment adjustments. Additionally, educating families about genetic findings fosters informed decision-making and engagement in innovative therapies, ensuring the child receives optimal care.
  • Patient and Family Empowerment: Involving families in therapeutic decision-making and research is particularly impactful in pediatric epilepsy [41]. For instance, educating parents about the potential benefits of genetic testing can lead to earlier identification of mutations such as SCN1A, allowing them to advocate for targeted therapies like fenfluramine for Dravet Syndrome. Additionally, involving families in clinical trials fosters a deeper understanding of available treatments and enhances engagement in the child’s care plan, ultimately improving outcomes and quality of life.
  • Strategies to increase affordability and improve equitable access: To increase the affordability and improve equitable access to precision medicine and therapy, global collaborations could play a pivotal role. By fostering partnerships between governments, healthcare providers, pharmaceutical companies, and research institutions, the cost burden of developing and implementing precision therapies can be shared. Such collaborations could enable pooled resources for research and development, making therapies more affordable and widely accessible, particularly in low- and middle-income countries. Through shared knowledge, economies of scale, and harmonized policies, these global efforts could address disparities in access, ensuring that the benefits of precision medicine reach diverse populations around the world.

7. Conclusions

Precision medicine heralds a transformative era in managing pediatric epileptic and developmental encephalopathies (EDEs) by transcending phenotype-based approaches and addressing the root causes of these disorders. By integrating genetic and molecular insights into diagnostic and therapeutic workflows, precision therapies have the potential to significantly improve clinical outcomes and quality of life for affected individuals. Despite its promise, the path to widespread implementation of precision therapy remains fraught with challenges. Diagnostic delays, therapeutic accessibility, limited clinical evidence, and knowledge gaps in genomic medicine continue to hinder progress. Furthermore, even established precision therapies, such as pyridoxine (Vitamin B6) for Pyridoxine-Dependent Epilepsy (PDE) and the ketogenic diet for GLUT1-Deficiency Syndrome (GLUT1-DS), highlight the limitations of current approaches [42], as they fail to completely mitigate the neurodevelopmental and neurological consequences of these conditions. Addressing these challenges requires a comprehensive, collaborative approach that includes standardizing genetic testing, expanding therapeutic innovation, fostering global collaboration, and equipping healthcare providers with genomic expertise. Equally important is the need to involve patients and families in every step of the diagnostic and therapeutic journey, empowering them to make informed decisions and participate actively in research and care. As the field of precision medicine continues to evolve, the focus must shift toward developing therapies that not only control symptoms, such as seizures, but also correct the underlying genetic or molecular defects. Achieving this vision will necessitate robust investment in research, policy reform, and international cooperation to ensure equitable access to these life-changing interventions. By embracing this paradigm shift, precision medicine can unlock new opportunities for individualized care, paving the way for a future where no patient is left behind.

Author Contributions

Conceptualization, methodology, writing—original draft preparation, R.F. and P.P.; writing—review and editing, V.S.; supervision, R.F. and P.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study.

Conflicts of Interest

The authors declare no conflicts of interest.

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Table 1. Precision Therapy for EDEs.
Table 1. Precision Therapy for EDEs.
CategoryExamplesImpact
Diagnostic ToolsNGS, WES, WGS, MRI spectroscopyEnhanced identification of genetic mutations and structural abnormalities
Gene-Specific TargetingSodium channel modulators (SCN2A), ASOs (Angelman), CRISPRAddressing underlying genetic causes
Pathway-Specific InterventionsmTOR inhibitors (TSC), AMPA modulators (GRIN2A), neuroprotective agents (POLG)Improved seizure control and neuroprotection
Metabolic InterventionsPyridoxine (Vitamin B6) for PDE, Ketogenic diet for GLUT1-DSReducing seizures and addressing metabolic dysfunctions
BiomarkersCSF neurofilament light chain, EEG patternsReal-time monitoring of disease progression and treatment efficacy
Therapeutic ChallengesLimited access, high costs, lack of RCTsHinder widespread adoption and equitable implementation
Future StrategiesGenetic testing standardization, global collaboration, educationAccelerating transition to precision medicine
NGS: next-generation sequencing; WES: whole-exome sequencing; WGS: whole-genome sequencing; MRI: Magnetic Resonance Imaging; SCN2A: sodium voltage-gated channel alpha subunit 2; ASOs: antisense oligonucleotides; CRISPR: clustered regularly interspaced short palindromic repeats; mTOR: mechanistic target of rapamycin; TSC: tuberous sclerosis complex; AMPA: α-Ammino-3-idrossi-5-Metil-4-isossazol-Propionic Acid; GRIN2A: glutamate ionotropic receptor NMDA type subunit 2A; POLG: DNA polymerase gamma; PDE: Pyridoxine-Dependent Epilepsy; GLUT1-DS: Glucose transporter type 1 deficiency syndrome; CSF: Cerebrospinal fluid; EEG: electroencephalogram; RCTs: Randomised controlled trials.
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Falsaperla, R.; Sortino, V.; Pavone, P. Is Precision Therapy in Infantile-Onset Epileptic Encephalopathies Still Too Far to Call Upon? Appl. Sci. 2025, 15, 2372. https://doi.org/10.3390/app15052372

AMA Style

Falsaperla R, Sortino V, Pavone P. Is Precision Therapy in Infantile-Onset Epileptic Encephalopathies Still Too Far to Call Upon? Applied Sciences. 2025; 15(5):2372. https://doi.org/10.3390/app15052372

Chicago/Turabian Style

Falsaperla, Raffaele, Vincenzo Sortino, and Piero Pavone. 2025. "Is Precision Therapy in Infantile-Onset Epileptic Encephalopathies Still Too Far to Call Upon?" Applied Sciences 15, no. 5: 2372. https://doi.org/10.3390/app15052372

APA Style

Falsaperla, R., Sortino, V., & Pavone, P. (2025). Is Precision Therapy in Infantile-Onset Epileptic Encephalopathies Still Too Far to Call Upon? Applied Sciences, 15(5), 2372. https://doi.org/10.3390/app15052372

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