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. 2022 Jun 6;4(3):fcac144. doi: 10.1093/braincomms/fcac144

Figure 8.

Figure 8

4-Phenylbutyrate acid (PBA) alone reduced seizures in mutation knockin mice. (A) Schematic depiction of experimental paradigm for EEG recordings and PBA treatment. (B) Representative EEG recordings show that the heterozygous SLC6A1+/S295L (het) KI mice had frequent absence like spike wave discharges (SWDs) and some myoclonic jerks during baseline recordings. (C) Comparison of EEG traces recorded after the vehicle (normal saline 100 µL) treated or after treatment with PBA (100 mg/kg, i.p., single dose, daily) for 7 days. (D) Graph showing the total number of 5–7 Hz SWDs calculated by Seizure Pro during 48 h recordings after vehicle or PBA treatment. PBA treatment (100 mg/kg, i.p., single dose, daily) for 7 days reduced seizure activity. **P < 0.01; versus vehicle treated, paired t test, N = 6 animals. Values were expressed as mean ± SEM. (E, F) Graph showing the percentage of seizure remaining (E) and seizure reduction (F) in each mouse after PBA treatment (N = 6 animals, paired t test). (G) We propose a dual therapy as a feasible approach for treating SLC6A1 variants and other genetic disorders by boosting the wildtype allele, removing the mutant allele and ER stress with PBA.