Fig. 3: Re-expression of Scn1a gene after symptoms onset rescues seizures in DS mice.

a Schematics depicting the experimental timeline, with Scn1a^Stop/+ mice undergoing PHP.eB-Ctrl or PHP.eB-Cre tail vein injection at P30, followed by EEG transmitter implantation at P45, two weeks of EEG recordings and, seizure thermal induction at P60. Created with BioRender.com. b Survival of Scn1a^Stop/+ (n = 23), Scn1a^Stop/+ -Cre (n = 11) monitored out to 90 days (**p = 0.0018; Log-rank Mantel-Cox test). c Raster plot showing all generalized tonic-clonic seizures (Racine scale stages 4 and 5) in 8 Scn1a^Stop/+-Ctrl injected mice and 9 Scn1a^Stop/+-Cre mice subjected to video-EEG recordings. d Pie chart (right panel) showing the proportion of Ctrl- and PHP.eB-Cre-injected Scn1a^Stop/+ mice with or without spontaneous seizures (p = 0.0004; Fisher’s exact test). e Cumulative seizure number (left), average daily seizure frequency in two weeks of recordings (middle) and average seizure duration (right), in Scn1a^Stop/+ -Ctrl (n = 8) and -Cre (n = 9) injected mice. (****p < 0.0001, two-tailed unpaired test). Data are shown as mean ± SEM, with dots representing individual mice. f Left, schematic of electrode placement in left (L) and right (R) cortical hemispheres for EEG recordings (from bregma AP -1; ML ± 1). Right, Representative traces of EEG recordings of Scn1a^Stop/+ -Ctrl injected during an ictal episode and Scn1a^Stop/+ -Cre injected. g Percentage of Scn1a^Stop/+ -Ctrl and Scn1a^Stop/+ -Cre mice remaining seizure-free after thermal induction (left) (n = 8 Scn1a^Stop/+-Ctrl and n = 9 for for Scn1a^Stop/+ -Cre (****p < 0.0001; Mantel-Cox log-rank test). h Pie charts showing the percentage of Scn1a^Stop/+-Ctrl and for Scn1a^Stop/+ -Cre mice with or without induced thermal seizures (p = 0.0004; two-sided Fisher’s exact test). Source data are provided as a Source Data file.