Pharmacotherapeutic management of seizures in patients with Angleman Syndrome

ABSTRACT

Introduction

Approximately 80–90% of patients with Angelman syndrome (AS) develop childhood-onset intractable seizures with major negative impact on the quality of life. Thus adequate management of seizures is the most critical priority to improve health-related quality of life in children with AS.

Areas covered

The primary focus of the review is on pharmacotherapeutic management of seizures. To better comprehend pharmacotherapeutic decision-making, the first section of the paper briefly examines epileptogenesis and polymorphic seizure morphologies related to AS. Next, the review explores individual antiseizure medications (ASMs) and their potential therapeutic utility. Lastly, some future and emerging treatment options are discussed that can transform the management of seizures in patients with AS.

Expert Opinion

Evidence for treating seizures in AS mainly derives from low-quality studies. Levetiracetam and clobazam are the most commonly used ASMs. Although the potential utility of several other ASMs(valproate, topiramate, lamotrigine, ethosuximide, clonazepam) has been well documented for some time, the treatment landscape may rapidly evolve due to the availability of newer and better tolerated ASMs(cannabidiol oil, brivaracetam, perampanel). In addition, a better understanding of the underlying pathogenesis and the development of molecular therapeutics offer hope for precision therapies for seizures.

KEYWORDS:

• Angelman syndrome
• UBE3A
• epilepsy
• seizures
• medicine
• gene
• molecular therapy

Article highlights

• Approximately 80-90% of patients with Angelman syndrome(AS) develop childhood-onset intractable seizures

• Levetiracetam and clobazam are the first-line antiseizure medications(ASMs) for AS-associated seizures.

• Several other ASMs(valproate, topiramate, lamotrigine, ethosuximide, clonazepam) can be effective in seizure management.

• Although certain newer ASMs (cannabidiol oil, brivaracetam, and perampanel) may have better side-effect profile, clinical evidence is currently insufficient.

• More than 15 different precision(restoration of nonfunctional UBE3A protein) or downstream(repair molecular and synaptic abnormalities by using small molecule drugs) therapeutic approaches are in the preclinical and early clinical developmental stages.

Declaration of interest

The author has no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.