Epilepsy: key experimental therapeutics in early clinical development

Area of Science:

• Neurology
• Pharmacology
• Epileptology

Background:

• Current antiseizure medications (ASMs) are not etiology-specific and control seizures in only two-thirds of epilepsy cases.
• Existing ASMs target focal or generalized epilepsies irrespective of cause.
• Investigational ASMs are increasingly targeting rare or orphan epilepsy syndromes.

Purpose of the Study:

• To review ASMs in clinical development.
• To discuss novel drug targets and mechanisms of action.
• To outline therapies with potential disease-modifying effects.

Main Methods:

• Identified investigational drugs using the Epilepsy Foundation pipeline tracker.
• Reviewed conference proceedings from recent epilepsy drug conferences (XV AEDD, XIV EILAT).
• Analyzed drugs targeting GABA, T-type calcium channels, 5-HT, and potassium channels, as well as those with unknown/multiple mechanisms.

Main Results:

• ASMs in development target novel receptors (e.g., GABA, T-type calcium channels) and epileptogenesis.
• Investigational drugs include those with unknown/multiple mechanisms (cannabinoids, carisbamate, cenobamate).
• Disease-modifying therapies in development include gene-targeted treatments, mTOR inhibitors, and inflammation-targeted treatments.

Conclusions:

• Novel ASMs targeting specific mechanisms offer promise for seizure control and preventing epileptogenesis.
• Assessing disease-modifying agents may require novel clinical trial designs.
• Precision medicine for genetic epilepsies holds potential for seizure control and brain health restoration.