OtherMolecular autism2022

Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K).

Stefania Beretta, Laura Gritti, Luisa Ponzoni and 5 others

PMID 34980259

WHAT IT FOUND

Deleting the eEF2K gene or inhibiting it with a drug reduced seizures and improved memory and motor skills in mice with Dravet syndrome.

This is preclinical work in mice, so it does not yet show whether these treatments work in children.

Key findings

01Genetic deletion of eEF2K in Dravet syndrome mice normalized EEG spike counts to levels seen in healthy control mice.

02Pharmacological inhibition of eEF2K with A484954 reduced EEG spikes and improved episodic memory in Dravet syndrome mice.

03eEF2K deletion rescued motor coordination deficits, stereotyped grooming, and spatial memory impairments in Dravet syndrome mice.

STILL TO COME

How it was doneWhat they found

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What it does not show

This is a preclinical study in mice, so findings do not directly translate to human patients. The molecular mechanism causing increased eEF2 phosphorylation in Dravet syndrome was not determined. The pharmacological study was short (10 days) and did not assess whether the drug restores inhibitory synaptic transmission or addresses all behavioral deficits. The study did not investigate long-term side effects of eEF2K inhibition.

Declared interests

Funding was provided by Fondazione Telethon, Fondation Jérôme Lejeune, and Regione Lombardia. No specific conflicts of interest were declared by the authors.

The easy way to misread this

Do not interpret these results as evidence that eEF2K inhibitors are a ready clinical treatment for Dravet syndrome. The study was conducted in mice, and the pharmacological intervention used a specific implant delivery system not yet tested in humans.

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The study

Participants
26 mice for EEG; 190 mice for behavioral analyses
Certainty of evidence
Low

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    Cite

    Stefania Beretta, Laura Gritti, Luisa Ponzoni, et al. Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K). Molecular autism. 2022.

    Read the original