De novo loss-of-function mutations in SCN1A are the main cause of Dravet syndrome, a catastrophic encephalopathy characterized by recurrent early-life febrile seizures, a number of other afebrile seizure types that are often refractory to treatment, and behavioral abnormalities including social deficits, motor dysfunction, and cognitive impairment. This research team previously demonstrated that the reversible acetylcholinesterase inhibitor, Huperzine A, increases seizure resistance in Scn1a mutants.
In the present study, the team evaluated the therapeutic potential of donepezil, a reversible acetylcholinesterase inhibitor approved by the FDA, in a mouse model of Dravet syndrome (Scn1a +/-). The team found that donepezil conferred robust protection against induced seizures in Scn1a +/- mutants.