Rationale Fenfluramine (FFA) provides clinically significant reductions in convulsive seizure frequency and improved executive function in patients with Dravet syndrome (DS). FFA also reduces sudden unexpected death in epilepsy (SUDEP) in mouse models of DS. We investigated FFA effects upon survival, myelination, and neuroinflammation in a mouse model of DS.

Methods scn1a+/- mice (DS mice) were treated subcutaneously with FFA. FFPE sagittal brain sections were immunostained with D-MBP antibody for degenerated myelin and CD11b antibody for inflamma- tory microglia.

Results In animals receiving FFA, the mortality rate was reduced to 24% (P< 0.01; Figure 1). Degenerated myelin was enriched in DS mouse cortex and hippocampus compared to wild-type controls. FFA treatment reduced degenerated myelin.

Conclusion This is the first report of increased survival and reductions in myelin degeneration and neuro- inflammation in DS mice treated with FFA. Improved survival and reduced myelin damage and neuroin- flammation demonstrates the claim that FFA exhibits disease-modifying effects in animal models of DS.