Yet despite these clear advances in our understanding of interneuronal biology and its importance to the stabilization of cortical circuits, the pool of epileptic patients appropriate for any interneuron-based cell therapeutic strategy might prove limited. First, a number of effective medical and surgical treatments for epilepsy are already available, such that a cell-based treatment approach would only be tenable for those patients substantially refractory to all currently approved therapeutic modalities. Second, the risk of interneuronal engraftment-associated changes in other cognitive and functional domains must be considered; the effects of interneuronal integration into existing – and already aberrant – mature neuronal networks has yet to be established in primates, much less humans. Moreover, such effects may prove both variable and unpredictable from patient to patient, depending on disease history and the local tissue environment. In light of these considerations - over and above the more generic risks of long-term intracerebral colonization with PSC-derivatives - the clinical translation of this approach to seizure management will likely be both slow and cautious. Nonetheless, its promise of ensuring durable seizure control in otherwise refractory, and often terribly disabled, patients is so attractive as to justify intense investigation of this emerging clinical opportunity.
