Synaptic GABAA receptor (GABAAR) internalization contributes to the
drug resistant nature of super-refractory
status epilepticus (SRSE).
Ganaxolone is a 3β-methylated synthetic analog of the endogenous
neuroactive steroid,
allopregnanolone, that has positive allosteric modulatory activity on synaptic and extrasynaptic GABAA receptors.
Ganaxolone is currently in clinical trials to treat rare pediatric
seizure disorders and established and refractory SE. Two pediatric patients with SRSE (age 17 and age 7) were treated under emergency
investigational new drug (E-IND) applications with intravenous (IV)
ganaxolone administered as an initial bolus and a maintenance infusion for up to 4.5 days with intermittent IV boluses as-needed followed by taper on day 5 and transitioned to chronic treatment using
ganaxolone suspension. Adjunctive
ganaxolone was effective in terminating SRSE in both patients, safely permitting IV
anesthetics to be weaned. Seizure control has been maintained after transitioning to enteric
ganaxolone. Further investigation of
ganaxolone as a safe and effective treatment for SRSE is warranted.