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Epilepsia 2019-Nov

Personalized medicine: Vinpocetine to reverse effects of GABRB3 mutation.

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Santoshi Billakota
J Andresen
Bryant Gay
Gregory Stewart
Nikolai Fedorov
Aaron Gerlach
Orrin Devinsky

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Abstracto

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.

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