The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome

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Glucagon-like peptide-1 (GLP-1) is a hormone that is secreted from intestinal cells after food ingestion, stimulates insulin secretion, and helps regulate blood sugar levels. It also binds to receptors in the brain and promotes satiety, thereby reducing food intake. For these reasons, GLP-1 analogs have become popular as second-line drugs to treat type 2 diabetes (ex. – Victoza, Byetta, Trulicity, Ozempic). With such popular use, GLP-1 has become anecdotally linked to improvements in various conditions, including Parkinson’s, Alzheimer’s, and MS. The current study asked whether any effect could be observed with respect to Dravet syndrome.

Heterozygous Dravet mice were created by knocking out one of the Scn1a genes, and they were treated with liraglutide (Victoza). At the cellular level, treatment increased the expression of the remaining Scn1a gene. At the functional level, liraglutide reduced seizure susceptibility and severity, and improved cognitive performance.

Further, it was found that treatment was neuroprotective and reduced the occurrence of apoptosis. Apoptosis is a process leading to neuronal cell death, that can become a vicious cycle – seizures can cause apoptosis, which in turn can promote the progression of epilepsy. The authors note that part of the neuroprotective effect was due to repressing the mTOR signaling pathway, which can be abnormally increased in epilepsy models and can mediate apoptosis.

Liu, S. et al. The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome. Front Pharmacol. 2020 Feb 28 [Epub ahead of print]. DOI: 10.3389/fphar.2020.00136.
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