Personalized medicine: Vinpocetine to reverse effects of GABRB3 mutation.
Adult
Dose-Response Relationship, Drug
Electroencephalography
/ drug effects
Female
HEK293 Cells
Humans
Lennox Gastaut Syndrome
/ diagnosis
Mutation
/ genetics
Neuroprotective Agents
/ pharmacology
Precision Medicine
/ methods
Receptors, GABA-A
/ genetics
Vinca Alkaloids
/ pharmacology
gamma-Aminobutyric Acid
/ pharmacology
Lennox-Gastaut
epilepsy
precision medicine
refractory
vinpocetine
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
26
09
2019
revised:
25
10
2019
accepted:
28
10
2019
pubmed:
23
11
2019
medline:
16
4
2020
entrez:
23
11
2019
Statut:
ppublish
Résumé
To screen a library of potential therapeutic compounds for a woman with Lennox-Gastaut syndrome due to a Y302C GABRB3 (c.905A>G) mutation. We compared the electrophysiological properties of cells with wild-type or the pathogenic GABRB3 mutation. Among 1320 compounds, multiple candidates enhanced GABRB3 channel conductance in cell models. Vinpocetine, an alkaloid derived from the periwinkle plant with anti-inflammatory properties and the ability to modulate sodium and channel channels, was the lead candidate based on efficacy and safety profile. Vinpocetine was administered as a dietary supplement over 6 months, reaching a dosage of 20 mg three times per day, and resulted in a sustained, dose-dependent reduction in spike-wave discharge frequency on electroencephalograms. Improved language and behavior were reported by family, and improvements in global impression of change surveys were observed by therapists blinded to intervention. Vinpocetine has potential efficacy in treating patients with this mutation and possibly other GABRB3 mutations or other forms of epilepsy. Additional studies on pharmacokinetics, potential drug interactions, and safety are needed.
Identifiants
pubmed: 31755996
doi: 10.1111/epi.16394
pmc: PMC7004153
doi:
Substances chimiques
GABRB3 protein, human
0
Neuroprotective Agents
0
Receptors, GABA-A
0
Vinca Alkaloids
0
vinpocetine
543512OBTC
gamma-Aminobutyric Acid
56-12-2
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2459-2465Informations de copyright
© 2019 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
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