Perampanel as precision therapy in rare genetic epilepsies

Media type: E-Article
Title: Perampanel as precision therapy in rare genetic epilepsies
Contributor: Nissenkorn, Andreea; Kluger, Gerhard; Schubert‐Bast, Susanne; Bayat, Allan; Bobylova, Marya; Bonanni, Paolo; Ceulemans, Berten; Coppola, Antonietta; Di Bonaventura, Carlo; Feucht, Martha; Fuchs, Anne; Gröppel, Gudrun; Heimer, Gali; Herdt, Brigitte; Kulikova, Sviatlana; Mukhin, Konstantin; Nicassio, Stefania; Orsini, Alessandro; Panagiotou, Maria; Pringsheim, Milka; Puest, Burkhard; Pylaeva, Olga; Ramantani, Georgia; Tsekoura, Maria; [...]
Published: Wiley, 2023
Published in: Epilepsia, 64 (2023) 4, Seite 866-874
Language: English
DOI: 10.1111/epi.17530
ISSN: 0013-9580; 1528-1167
Origination:
Footnote:
Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Perampanel, an antiseizure drug with α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ‐aminobutyric acid inhibition (e.g., <jats:italic>SCN1A</jats:italic>), overactive excitatory neurons (e.g., <jats:italic>SCN2A</jats:italic>, <jats:italic>SCN8A</jats:italic>), and variants in glutamate receptors (e.g., <jats:italic>GRIN2A</jats:italic>) hold special interest. We aimed to collect data from a large rare genetic epilepsy cohort treated with perampanel, to detect possible subgroups with high efficacy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This multicenter project was based on the framework of NETRE (Network for Therapy in Rare Epilepsies), a web of pediatric neurologists treating rare epilepsies. Retrospective data from patients with genetic epilepsies treated with perampanel were collected. Outcome measures were responder rate (50% seizure reduction), and percentage of seizure reduction after 3 months of treatment. Subgroups of etiologies with high efficacy were identified.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 137 patients with 79 different etiologies, aged 2 months to 61 years (mean = 15.48 ± 9.9 years), were enrolled. The mean dosage was 6.45 ± 2.47 mg, and treatment period was 2.0 ± 1.78 years (1.5 months–8 years). Sixty‐two patients (44.9%) were treated for >2 years. Ninety‐eight patients (71%) were responders, and 93 (67.4%) chose to continue therapy. The mean reduction in seizure frequency was 56.61% ± 34.36%. Sixty patients (43.5%) sustained >75% reduction in seizure frequency, including 38 (27.5%) with >90% reduction in seizure frequency. The following genes showed high treatment efficacy: <jats:italic>SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, POLG1, POLG2</jats:italic>, and <jats:italic>NEU1</jats:italic>. Eleven of 17 (64.7%) patients with Dravet syndrome due to an <jats:italic>SCN1A</jats:italic> pathogenic variant were responders to perampanel treatment; 35.3% of them had >90% seizure reduction. Other etiologies remarkable for >90% reduction in seizures were <jats:italic>GNAO1</jats:italic> and <jats:italic>PIGA</jats:italic>. Fourteen patients had a continuous spike and wave during sleep electroencephalographic pattern, and in six subjects perampanel reduced epileptiform activity.</jats:p></jats:sec><jats:sec><jats:title>Significance</jats:title><jats:p>Perampanel demonstrated high safety and efficacy in patients with rare genetic epilepsies, especially in <jats:italic>SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, CDKL5, NEU1</jats:italic>, and <jats:italic>POLG</jats:italic>, suggesting a targeted effect related to glutamate transmission.</jats:p></jats:sec>
Access State: Open Access

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