DS is a rare, severe, pediatric-onset genetic epileptic encephalopathy characterized by developmental delay and multiple types of difficult-to-treat seizures. In particular, convulsive seizures associated with DS are debilitating, prolonged, frequent, and drug-resistant in many cases, and they exacerbate the risk of missing developmental milestones. In addition, most children with DS exhibit comorbid cognitive, behavioral, motor, and sleep issues by the age of six, severely impacting both patient and caregiver quality of life.
Today, treatment selection in DS is largely trial and error, driven by a patient’s seizure phenotype and the neurologist’s perception of the optimal mix of AEDs to address those seizures. However, despite the availability of a wide array of AEDs—off-label and approved, branded and generic—that are prescribed adjunctively, a significant percentage of DS patients are refractory to current therapies. Consequently, new and improved AED / anti-seizure medications are needed; a range are in development for DS (and other rare epilepsy disorders) in various stages of development. Also, sorely needed are drugs that impact the underlying pathology of DS (i.e., DMTs); in partricular, experts believe that early intervention with a DMT, before a patients’ developmental delay is too severe, will be game changing. Most DMTs are in early-phase development and aim to address the SCN1A mutation, the underlying cause of the disease for ~80% of DS patients.