Effectiveness of add-on acetazolamide in children with drug-resistant CHD2-related epilepsy and in a zebrafish CHD2 model.

Autor: Melikishvili G; MediClubGeorgia Medical Center, Tbilisi, Georgia., Striano P; IRCCS Istituto Giannina Gaslini', Genova, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genoa, Italy., Shojeinia E; Centre for Molecular Medicine Norway (NCMM), University of Oslo, Oslo, Norway.; Institute for Orphan Drug Discovery, Bremerhaven, Germany., Gachechiladze T; MediClubGeorgia Medical Center, Tbilisi, Georgia., Kurua E; MediClubGeorgia Medical Center, Tbilisi, Georgia., Tabatadze N; MediClubGeorgia Medical Center, Tbilisi, Georgia., Melikishvili M; MediClubGeorgia Medical Center, Tbilisi, Georgia., Koniashvili O; MediClubGeorgia Medical Center, Tbilisi, Georgia., Khachiashvili G; MediClubGeorgia Medical Center, Tbilisi, Georgia., Epitashvili N; Epilepsy Center, Medical Center, University of Freiburg, Freiburg, Germany., Rimma G; Kazan Federal University, Kazan, Russia., Belyaev O; Department of Neurology, Institute of Continuous Medical Education, Volgograd State Medical University, Volgograd, Russia., Tomenko T; Ural Federal University, Ekaterinburg, Russia., Kharytonov V; Clinical Hospital 'Psychiatry', Kiev, Ukraine., Guliyeva U; MediClub Hospital, Baku, Azerbaijan., Esguerra CV; Centre for Molecular Medicine Norway (NCMM), University of Oslo, Oslo, Norway., Crawford AD; Institute for Orphan Drug Discovery, Bremerhaven, Germany., Dulac O; AdPueriVitam, Antony, France.
Jazyk: angličtina
Zdroj: Epilepsia open [Epilepsia Open] 2024 Oct; Vol. 9 (5), pp. 1972-1980. Date of Electronic Publication: 2024 Aug 24.
DOI: 10.1002/epi4.13034
Abstrakt: CHD2-related epilepsy is characterized by early-onset photosensitive myoclonic epilepsy with developmental delay and a high rate of pharmacoresistance. We sought to evaluate the efficacy of acetazolamide (ACZ) in CHD2-related epilepsy, due to ACZ's unexpected efficacy in our first patient harboring a pathogenic CHD2 variant. We collected patients from different Eastern European countries with drug-resistant CHD2-related epilepsy who were then treated with ACZ. Patients underwent video EEG before and during ACZ treatment. In a zebrafish model of CHD2-related epilepsy, ictal-like events were recorded 5 days post-fertilization after overnight ACZ exposure. Developmental delay preceded the onset of seizures in 10 of the 12 patients. Four had ataxia, and 6 exhibited autistic features. Seizures, primarily myoclonic, began at an average age of 3.4 years and were photosensitive in all 12 patients. Add-on ACZ treatment controlled photosensitive seizures in all patients: 6 became seizure-free, and in the remaining 6, seizure frequency decreased by over 75%. Four patients transitioned to ACZ monotherapy. The median follow-up was 13 months. In the zebrafish model, ACZ exposure reduced ictal-like events by 72%. ACZ, a well-tolerated and cost-effective medication, could be a good option for CHD2-related epilepsy, predominantly manifesting with myoclonic seizures and photosensitivity. PLAIN LANGUAGE SUMMARY: Epilepsy associated with CHD2 mutations is often pharmacoresistant and associated with developmental delay and eventually ataxia. There are several generalized seizure types, including generalized tonic-clonic seizures, but the most characteristic are jerks triggered by light stimulation. We collected 12 patients who received acetazolamide, a drug usually given as a diuretic and registered as a mild antiseizure medication. All jerks triggered by light disappeared while the frequency of spontaneous seizures decreased by over 75%. Further studies are needed to confirm this promising finding and identify the mechanism by which an old compound seems to have such a specific antiseizure effect.
(© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
Externí odkaz: