A novel approach of targeting refractory epilepsy: Need of an hour

New Trends and Most Promising Therapeutic Strategies for Epilepsy Treatment

“…P-glycoproteins are the final encoded product of the human multi-drug resistance-1 ( MDR-1 ) gene, and play a role in treatment response possibly inducing MDR ( 57 , 58 ). The increased activity of P-gps reduces clinically effective concentrations of ASMs despite adequate serum concentrations, reversing the anti-seizure effects on epileptogenic areas in the parenchyma of the brain ( 3 ).…”

“…Following the general rule that the higher the lipophilicity of a drug, the faster the entrance into the brain ( 59 ), available ASMs are very lipophilic, but more than one-third of the patients do not respond to treatment. The possible reason may be ASMs serve as P-gps substrates; secondly, the P-gps levels are higher ( 3 ). Different clinical studies had shown poor prognoses associated with MDR1 gene products, which gave rise to extensive experimental research on the P-gps ( 3 ).…”

“…The possible reason may be ASMs serve as P-gps substrates; secondly, the P-gps levels are higher ( 3 ). Different clinical studies had shown poor prognoses associated with MDR1 gene products, which gave rise to extensive experimental research on the P-gps ( 3 ). The adjunctive use of a P-gps inhibitor might counteract drug resistance and efficiently decrease seizure frequency.…”

“…Third-generation inhibitors have more advantages such as high specificity for P-gp, lack of non-specific cytotoxicity, relatively long duration of action with reversibility, and good oral bioavailability. However, despite their selectivity and potency, also this last generation of MDR modulators is far from being perfect and further studies will be needed to outline their effectiveness and safely overcome drug resistance ( 3 , 60 ). As pertains to clinical research, Iannetti et al ( 62 ) first demonstrated the action of verapamil in a case of prolonged refractory SE and then, subsequently on small series of other types of drug-resistant epilepsies ( 63 , 64 ).…”

“…Over 50 million people worldwide are affected by epilepsy and its causes remain partially elusive, leaving physicians, and patients an unclear insight into the etiology of the disease and the best treatment approach ( 2 ). Over than 30% of individuals do not respond to common anti-seizure medications (ASMs) and are addressed to as “drug-resistant,” a term which the International League Against Epilepsy (ILAE) applies to those patients who do not respond to the combination of two appropriately chosen and administered ASMs ( 3 , 4 ). Hence, a great deal of responsibility laid upon the research and development of innovative pharmacological and non-pharmacological approaches given a targeted approach, aiming at improving the symptoms of patients and their quality of life (QoL), together with that of the caregivers.…”