Current Treatments in AS and Efficacy

Quick Overview

The panel discussed the challenges of conducting clinical trials for rare diseases like Angelman syndrome. They highlighted the need for comparators, such as placebo controls or natural history controls, and the importance of outcome measures and biomarkers. They also emphasized the importance of supportive care and the potential benefits of participating in clinical trials, such as frequent follow-up and access to experts. The panel also discussed the challenges of proving the efficacy of targeted interventions and the need for long-term trials and disease-specific outcome measures. They mentioned the potential use of CBD as an additional treatment option, but noted that more research is needed. Overall, the panel stressed the importance of collaboration between researchers, clinicians, and families to advance the understanding and treatment of Angelman syndrome.


In this talk, we will discuss the current treatments available for Angelman Syndrome (AS) and their efficacy. We will also touch upon the challenges faced in conducting clinical trials for AS and the importance of participating in these trials. The information presented here is based on the discussions and presentations at the 2019 ASF Family Conference.

Older Treatment Trials

Before delving into the current treatments, it is important to understand some of the older treatment trials that have been conducted. These trials aimed to explore the effectiveness of various interventions in improving the symptoms and abilities of individuals with AS.

One such trial focused on methylation, which involved the use of folate and betaine to increase UBE3A production. The trial did not show significant improvements in outcome measures such as growth, exams, EEG, and language skills. However, there was a statistically significant difference in the reduction of hypermotoric behavior in the treatment group.

Another trial explored the use of multiple methylating agents, including folate, betaine, creatine, and vitamin B12. This trial also did not show significant improvements in outcome measures compared to a control group.

Current Treatments in Place

Dr. Duis and Dr. Thibert discussed the current treatments being used in their clinics. These treatments are based on best practice medical care and aim to provide supportive treatment for individuals with AS. They focus on managing symptoms such as seizures, sleep problems, anxiety, and gastrointestinal concerns.

For seizures, various medications such as Keppra, Onfi, and lamictal have been found to be effective. Dietary therapies, such as the ketogenic diet, have also shown positive results in managing seizures.

Sleep problems can be addressed through behavioral interventions, such as sleep training, and the use of medications like melatonin and clonidine.

Anxiety can be managed through behavior therapies, identifying triggers, and modifying daily routines. Medications such as Buspar and clonidine can also be used to alleviate anxiety symptoms.

Gastrointestinal concerns, including reflux, constipation, and hyperphagia, can be addressed through dietary modifications, medications, and behavioral interventions.

Challenges in Conducting Clinical Trials

Conducting clinical trials for AS presents several challenges. One of the main challenges is finding an appropriate comparator for the trial. This can involve using a waitlist control, placebo control, or natural history control, depending on the specific trial requirements.

Another challenge is the lack of established outcome measures for AS. Existing measures may not accurately capture the range of symptoms and abilities in individuals with AS. Developing disease-specific outcome measures is crucial for conducting effective trials.

There is also the issue of placebo effects and variability in responses to treatments. It is important to maintain an objective attitude and provide honest ratings during trials to avoid bias and inaccurate results.

Importance of Participating in Clinical Trials

Participating in clinical trials is crucial for advancing research and developing new treatments for AS. By participating, individuals with AS and their families contribute to the knowledge and understanding of the condition. They also have the opportunity to receive frequent follow-up, connect with experts in the field, and access assessments and evaluations that can be used for school and medical purposes.

However, it is important to remember that participating in a trial does not guarantee a positive outcome. Trials are conducted to test the efficacy and safety of interventions, and the results may vary for each individual.


Current treatments for AS focus on providing supportive care and managing symptoms such as seizures, sleep problems, anxiety, and gastrointestinal concerns. Conducting clinical trials for AS presents challenges, but they are essential for developing targeted treatments and improving the quality of life for individuals with AS. Participating in trials allows individuals and families to contribute to research and gain access to expert care and assessments.

Talk details

  • Title: Current Treatments in AS and Efficacy
  • Author(s): Jessica Duis, Mark Nespeca, Elizabeth Berry-Kravis, Ron Thibert
  • Author(s)’ affiliation: Vanderbilt University School of Medicine; UCSD; Rush University Medical Center; Massachusetts General Hospital
  • Publication date: 2019-09-06
  • Collection: 2019 ASF Family Conference