Computational approaches for innovative antiepileptic drug discovery

ABSTRACT

Introduction: Despite the approval of a large number of antiepileptic agents over the past 25 years, there has been no significant improvement in efficacy of treatments, with one third of patients suffering from intractable epilepsy. This scenario has prompted the search for innovative drug discovery solutions. While network pharmacology and explanations of the drug resistance phenomena have been proposed to drive the search for more efficacious therapeutic solutions, such alternative approaches have not fully taken hold within the antiepileptic drug discovery community so far.

Areas covered: Herein, the author discusses the impact that network pharmacology and the current hypotheses of refractory epilepsy and drug repurposing could have if integrated with anti-epileptic computer-aided discovery.

Expert opinion: With many complex diseases, the advancement in the understanding of disorder pathophysiology in addition to the contribution of systems biology have rapidly translated into the discovery of novel drug candidates. However, antiepileptic drug developers have fallen a little behind in this regard, with fewer examples of computer-aided antiepileptic drug design and network-based approximations appearing in scientific literature. New generation single-target agents have so far shown limited success in terms of enhanced efficacy; in contrast, multi-target agents could possibly demonstrate improved safety and efficacy.

KEYWORDS:

• Epilepsy
• refractory epilepsy
• network pharmacology
• systems biology
• multi-target agents
• hybrid molecules
• phenotypic screening
• QSAR
• drug repurposing
• drug design

Article highlights

• Last generation antiepileptic drugs have failed to meet the expectations regarding improved efficacy in the treatment of refractory patients.

• Novel strategies towards the development of new antiepileptic agents are required.

• Modern approaches (e.g. multi-target drugs, computer-guided drug design) that have been widely used to discover new treatments for other diseases of complex etiology have been underexplored in the case of epilepsy.

• Knowledge on the hypothetic causes of drug resistant epilepsy should be translated to the antiepileptic drug discovery field.

• Target-driven approaches towards antiepileptic drug discovery should be complemented with phenotypic-based approximations in line with the network pharmacology perspective.

• Systematic drug repurposing poses excellent opportunities for the antiepileptic drug discovery community.

This box summarizes key points contained in the article.

Declaration of interest

This author is a member of the Argentinean National Council of Scientific and Technical Research Council (CONICET). He has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The author’s work is funded by the Argentinean National Council of Scientific and Technical Research Council (CONICET).