Precision Therapeutics in Lennox–Gastaut Syndrome: Targeting Molecular Pathophysiology in a Developmental and Epileptic Encephalopathy

Children, Journal Year: 2025, Volume and Issue: 12(4), P. 481 - 481

Published: April 8, 2025

Lennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, distinctive electroencephalographic patterns. Current treatments primarily focus on symptom management through antiseizure medications (ASMs), dietary therapy, epilepsy surgery, neuromodulation, but often fail to address the underlying pathophysiology or improve outcomes. As genetic causes are identified in 30-40% of LGS cases, precision therapeutics targeting specific molecular mechanisms emerging as promising disease-modifying approaches. This narrative review explores therapeutic strategies for based pathophysiology, including channelopathies (SCN2A, SCN8A, KCNQ2, KCNA2, KCNT1, CACNA1A), receptor ligand dysfunction (GABA/glutamate systems), cell signaling abnormalities (mTOR pathway), synaptopathies (STXBP1, IQSEC2, DNM1), epigenetic dysregulation (CHD2), CDKL5 deficiency disorder. Treatment modalities discussed include traditional ASMs, targeted pharmacotherapy, antisense oligonucleotides, gene repurposing existing with mechanism-specific effects. Early intervention may not only control could also potentially prevent progression susceptible populations. Future directions developing computable phenotypes accurate diagnosis, refining subgrouping, enhancing drug development, advancing gene-based therapies, personalizing implementing adaptive clinical trial designs, ensuring equitable access While significant challenges remain, integrating biological insights innovative offers new hope transforming treatment from symptomatic disease modification.

Language: Английский

Current and Emerging Precision Therapies for Developmental and Epileptic Encephalopathies

Pediatric Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский