Novel and emerging therapeutics for genetic epilepsies

ABSTRACT

Introduction

Disease-specific treatments are available only for a minority of patients with genetic epilepsies, while the rest are treated with anticonvulsants, which are ineffective in almost one-third of patients.

Areas covered

Recently approved and the most effective emerging therapeutics under development for the treatment of genetic epilepsies are overviewed after systematic search and analysis of relevant literature.

Expert opinion

New and emerging drugs for genetic epilepsies exploit one of the two approaches: inhibiting hyperactive brain foci through blocking excitatory or augmenting inhibitory neurotransmission, or correcting the underlying genetic defect. The first is limited by insufficient selectivity of available compounds, and the second by imperfection of currently used vectors of genetic material, unselective and transient transgene expression. Besides, the treatment may come too late, after structural abnormalities and epilepsy deterioration takes place. However, with recent improvements, we can expect to see soon gradual decline in the number of patients with therapy-resistant genetic epilepsies.

KEYWORDS:

• Genetic epilepsy
• anticonvulsants
• efficacy
• safety
• drug development

Article highlights

• New and emerging drugs for genetic epilepsies exploit one of the two approaches: inhibiting hyperactive brain foci through blocking excitatory or augmenting inhibitory neurotransmission, or correcting underlying genetic defect.

• Causal relationship between certain genetic defect and seizure or epilepsy type is not always clear.

• Several genetic defects could be found in a patient with certain epilepsy type, and vice versa, the same genetic defect could be associated with various epilepsy types.

• There is a number of drugs recently approved for treatment of genetic epilepsies, and many more in various phases of preclinical or clinical development.

• Principles of precision medicine are increasingly employed in development of new drugs for genetic epilepsies.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This review was partially supported financially by Grant No 175007 from the Ministry of Education, Science and Technological Development, Republic of Serbia.