{
  "abstract": "Background: Developmental and epileptic encephalopathies (DEEs) and neurodevelopmental disorders with epilepsy (NDD-E) are etiologically heterogeneous conditions historically treated with syndrome-based, symptomatic approaches. Advances in genomic sequencing have identified monogenic causes across more than 900 genes, creating opportunities for mechanism-informed and disease-modifying precision therapies. Methods: For this narrative review, PubMed/MEDLINE and ClinicalTrials.gov were searched through September 2026 using disorder-, gene-, mechanism-, and therapeutic-modality-specific terms to identify mechanism-informed and disease-modifying therapies for monogenic DEEs and NDD-E. Results: Pathogenic mechanisms include gain- or loss-of-function ion-channel abnormalities, altered neurotransmitter receptor/transporter function, impaired synaptic signaling, dysregulated intracellular pathways, metabolic deficiencies, protein misfolding, and transcriptional or epigenetic dysregulation. Across genes such as SCN1A, SCN2A, SCN8A, KCNQ2, KCNT1, KCNA2, CACNA1A, GABA-receptor subunits, SLC6A1, GRIN genes, SYNGAP1, STXBP1, DNM1, SHANK3, TSC1/TSC2, GNAO1, UBE3A, MECP2, and TCF4, therapeutic strategies range from repurposed and mechanism-targeted pharmacologic agents (e.g., sodium- and potassium-channel modulators, mTOR inhibitors) to antisense oligonucleotides, RNA interference, gene replacement or augmentation, transcriptional activation, and genome editing. Several programs have advanced from preclinical proof of concept into early- and late-phase human trials, with variant-specific functional classification increasingly guiding therapy selection, particularly distinguishing gain-of-function from loss-of-function disease. Conclusions: Precision therapeutics are shifting the treatment paradigm for monogenic DEEs and NDD-E from empiric seizure control toward mechanism-based targeting of dysregulated molecular pathways and gene-based disease-modifying therapies. Realizing this potential will require functional variant classification, delivery technologies capable of durable and cell-appropriate target engagement, and trial designs incorporating developmental and biomarker outcomes beyond seizure frequency alone to demonstrate genuine disease modification.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, 1 Children’s Way, Little Rock, AR 72202, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Debopam Samanta",
      "orcid": "0000-0002-5154-8717"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/946k176xjkt01.bib",
  "cited_by": 0,
  "doi": "10.3390/jcm15207886",
  "fulltext_url": null,
  "id": "946k176xjkt01",
  "issns": [
    "2077-0383"
  ],
  "landing_url": "https://www.mdpi.com/2077-0383/15/20/7886",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2738|Epilepsy research and treatment"
    ]
  ],
  "openalex": "W7221652069",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/946k176xjkt01.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:00Z",
      "native_id": "10.3390/jcm15207886",
      "source": "crossref",
      "url": "https://www.mdpi.com/2077-0383/15/20/7886"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Epilepsy research and treatment",
      "subfield": "psychiatry"
    }
  ],
  "title": "Precision Therapeutics for Monogenic Epilepsies: From Molecular Mechanisms to Disease Modification in Developmental and Epileptic Encephalopathies and Neurodevelopmental Disorders with Epilepsy",
  "title_text": "Precision Therapeutics for Monogenic Epilepsies: From Molecular Mechanisms to Disease Modification in Developmental and Epileptic Encephalopathies and Neurodevelopmental Disorders with Epilepsy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:00Z",
  "url": "https://research.draconitic.com/paper/946k176xjkt01",
  "venue": "Journal of Clinical Medicine",
  "versions": []
}