A complex systems view on the current hypotheses of epilepsy pharmacoresistance

Author(s)

Servilha-Menezes, Gabriel ; Garcia-Cairasco, Norberto

• Document type: Journal article
• Source: EPILEPSIA OPEN; v. N/A, p. 15-pg., 2022-03-11.

Abstract

Drug-resistant epilepsy remains to this day as a highly prevalent condition affecting around one-third of patients with epilepsy, despite all the research and the development of several new antiseizure medications (ASMs) over the last decades. Epilepsies are multifactorial complex diseases, commonly associated with psychiatric, neurological, and somatic comorbidities. Thus, to solve the puzzling problem of pharmacoresistance, the diagnosis and modeling of epilepsy and comorbidities need to change toward a complex system approach. In this review, we have summarized the sequence of events for the definition of epilepsies and comorbidities, the search for mechanisms, and the major hypotheses of pharmacoresistance, drawing attention to some of the many converging aspects between the proposed mechanisms, their supporting evidence, and comorbidities-related alterations. The use of systems biology applied to epileptology may lead to the discovery of new targets and the development of new ASMs, as may advance our understanding of the epilepsies and their comorbidities, providing much deeper insight on multidrug pharmacoresistance. (AU)

• FAPESP's process: 19/02787-4 - Effects of cannabidiol vehiculated in nanoemulsion in rats submitted to the chemical model of temporal lobe epilepsy
• Grantee: Gabriel Servilha Menezes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/05957-8 - Epilepsies and neuropsyquiatric comorbidities: characterization of the effects of the treatment with cannabidiol and HUF-101 in in vivo and in vitro experimental models
• Grantee: Norberto Garcia Cairasco
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50891-1 - INCT 2014: Translational Medicine
• Grantee: Jaime Eduardo Cecilio Hallak
• Support Opportunities: Research Projects - Thematic Grants