Current and emerging treatment options for Angelman syndrome

ABSTRACTIntroduction Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, limited expressive language, epilepsy, and motor impairment. Angelman syndrome is caused by haploinsufficiency of the UBE3A gene on the maternal copy of chromosome 15. There have been ongoing advances in the understanding of neurological, behavioral, and sleep-based problems and associated treatments for patients with AS. These results along with gene-based therapies entering into clinical development prompted this review. Areas covered The authors summarize the research basis describing phenomenology of epilepsy and behavioral concerns such as hyperactivity behavior, aggression, self-injury, repetitive behavior, and sleep disorder. The evidence for recent treatment advances in these target symptom domains of concern is reviewed, and the potential for emerging gene therapy treatments is considered.Expert opinion The prospect for emerging gene therapies means that increasing efforts should be directed toward the early identification of AS implemented equitably. Recent studies emphasize the important role of behavioral therapy in addressing mental health concerns such as aggression and disordered sleep.Keywords: Angelman SyndromeTreatmentBehaviorSleep DisorderEpilepsyAntisense oligonucleotide therapy Article highlights Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, limited expressive language, epilepsy, sleep disorder, motor impairment, and behavioral challenges.The treatment of epilepsy in AS includes first-line treatment with clobazam or levetiracetam with the consideration of dietary therapy including LGIT or the ketogenic diet for those with insufficient response.Speech therapy and behavioral interventions that improve communication and address attention seeking behaviors may help reduce aggression and self-injury in patients with AS.Treatments for anxiety including buspirone, clonazepam, and propranolol may reduce aggressive behaviors, and atypical antipsychotics may be considered in severe cases.Behavioral therapy can be effective for the treatment of sleep disorder in AS by addressing separation challenges at bedtime.Recent research highlights the promise of Antisense Oligonucleotide Therapies (ASOs) in treating the underlying genetic deficit in AS and early phase trials are currently underway to explore their benefits and risks.Declaration of interestCJ Keary declares receiving research funding from Maplight Therapeutics and has serviced on the scientific advisory committees of Ionis/Biogen Idec. CJ McDougle, meanwhile, has served as a consultant for Acadia Pharmaceuticals and Sage Therapeutics and has received royalties from Oxford University Press and Springer Publishing. The authors have 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.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis work was supported by the Angelman Syndrome Foundation and the Nancy Lurie Marks Family Foundation.