Increased activity of TrkB in synapses ipsilateral to the amygdala within the hippocampus was "fleeting," he emphasized, peaking at 6-24 hours and no longer present after a week following status epilepticus (J. Neurosci. 2010;30:6188-96).
The identification of a "critical period" for molecular events setting the stage for future seizures raises the enticing possibility of designing a brief intervention to halt the process, Dr. McNamara said.
Dr. McNamara and his team put this theory to the test by introducing a TrkB inhibitor to genetically engineered mice soon after they had experienced an episode of status epilepticus. This prevented subsequent seizures or sharply reduced their frequency.
"Can we identify a drug – a.k.a. ‘magic bullet’ – to inhibit TrkB or causal downstream signaling pathway [in humans]? I think that globally in this field there is progress that invites optimism," Dr. McNamara said.
Such an intervention could potentially prevent development of a life-altering form of epilepsy using a short-term strategy.
"Limiting drug treatment to a week or two following status epilepticus minimizes unwanted effects inherent in lifelong drug exposure," he noted.
How early would one need to intervene following status epilepticus?
"That is an incredibly important question," he said in response to an audience query about timing. "We hope that [the National Institute for Neurological Disorders and Stroke] will continue its support so we can answer that."
Dr. Berkovic reported receiving honoraria from UCB Pharma and Wolters Kluwer. Dr. McNamara disclosed that he is a consultant for Pappas Ventures and founder and member of the board of directors of NeurOp.
Courtesy Dr. Samuel F. Berkovic
Dr. Samuel F. Berkovic