AS Research & Development Update, Part 2

Quick Overview

This update provides information on the progress of research and development for Angelman Syndrome (AS). The panel discusses various topics including the definition of IND (Investigational New Drug Application), the genetic subclasses targeted, the age groups to be included in the trials, the expected benefits of the treatments, the administration of the therapeutics, the selection of study participants, the timeline for clinical trials, the collaboration on outcome measures, the collection of natural history study data, and the cost of the therapies. The panel emphasizes the importance of collaboration between researchers, caregivers, and advocacy groups, and encourages the community to stay informed and engaged in the research process.


In this update, we will be addressing some of the questions that have been submitted in advance, as well as questions from the wider community. We will cover topics such as the genetic subclasses being targeted, the ages that will be targeted in the trials, the expected benefits of the treatments, the administration of the therapeutics, and the timeline for the clinical trials. We will also discuss the importance of collaboration and the collection of natural history study data. Finally, we will touch on the cost of the therapies and the challenges of acquiring structured and unstructured data in a developmentally disabled population.

Genetic Subclasses and Targeted Ages

The first question we will address is what genetic subclasses will be targeted in the trials. Matt During mentioned that they will be targeting all the different genetic subclasses. Eugene and Jodi also confirmed that they will be targeting all genotypes of Angelman Syndrome.

In terms of the ages that will be targeted, Matt mentioned that their initial trial will involve individuals aged 16 and above, with plans to move into a younger population later on. The goal is to eventually include individuals of all ages in the clinical trials.

Benefits in Children and Adults

The next question is whether the treatments are anticipated to work only in children or also be beneficial to adults. Eugene mentioned that there are some aspects of the disease that may be more responsive in younger populations, but it is possible that UBE3A restitution or correction could address significant impairments in adults as well. However, more research is needed to determine the exact effects of the treatments in different age groups.

Jodi and Matt also agreed that it is difficult to predict whether the treatments will be more effective in young or old individuals. They emphasized the importance of early intervention and the potential for greater long-term gain in younger children.

Benefits in Different Genetic Subclasses

The question of whether there are any benefits specific to the UPD group or other genetic subclasses was raised. Eugene mentioned that in theory, there may be some differences in response among different genotypes, but it is difficult to predict at this stage. Jodi added that the animal models used in their studies reflect UV mutations, not deletions or UPD, so there may be some differences in response to the treatments.

Study Participants and Endpoints

The question of what is expected of study participants was also addressed. Matt mentioned that there will be a commitment required from participants, including regular visits to the centers and follow-up appointments. The exact number of visits and time frames will depend on the specific trial design.

The selection of study participants will be based on the eligibility criteria outlined in the study protocol. Phase 1 studies are usually more restrictive, focusing on a specific subset of patients to assess safety. The investigators at each site will have a thorough understanding of the protocol and will be able to determine whether an individual qualifies for the trial.

Administration of Therapeutics

The question of how the therapeutics will be administered was also raised. Matt mentioned that Gaboxadol is an orally active drug, so it will be administered in pill form. Eugene and Jodi mentioned that their approaches will likely involve intrathecal injections, similar to an epidural procedure. These injections will need to be done by trained neurologists or anesthesiologists in a hospital setting.

Lifelong Monitoring and Side Effects

The question of whether the treatments will need to be taken and monitored for a lifetime was raised. Eugene mentioned that it is difficult to predict at this stage, but it is possible that the treatments may not need to be administered for a lifetime, especially in younger individuals. However, more research is needed to determine the long-term effects of the treatments.

In terms of side effects, Matt mentioned that all drugs have side effects to some extent. The goal is to minimize side effects and monitor them closely. The side effect profile of Gaboxadol has been favorable so far, with manageable reactions such as headaches and back pain. The side effects of the other treatments are still being studied.

Timeline for Clinical Trials

The question of the timeline for clinical trials was also addressed. The timeline will depend on various factors, including the approval of the Investigational New Drug (IND) application. Once the IND is approved, the trials can begin, with the initial Phase 1 study lasting around one to two years. The timeline for Phase 2 and Phase 3 trials will depend on the outcomes of the Phase 1 study. Overall, the process from filing the IND to approval of a drug can take several years.

Collaboration on Outcome Measures

The importance of collaboration on outcome measures was emphasized. It is crucial to work together to identify and develop meaningful outcome measures that capture the real value of the treatments. Collaboration with patient advocacy groups, clinicians, and foundations can help in refining and validating these measures.

Collection of Natural History Study Data

The question of the collection of natural history study data was also raised. It was agreed that collecting additional longitudinal data and conducting surveys can be valuable in preparing for clinical trials. This data can help in developing outcome measures and providing a baseline for comparison in future trials.

Assessing Research Findings

The question of how parents and caregivers can assess the value and credibility of research findings was also addressed. It was recommended to gather information from trusted sources such as foundations, clinicians, and advocacy groups. These sources can provide a more digestible and reliable interpretation of complex scientific data.

Future Programs

The question of whether there are other programs that will be advancing in the clinic in the near future was raised. It was mentioned that there are a lot of programs in the pipeline, but many of them are still at an early stage and not ready for clinical trials. However, there is a lot of interest and progress in exploring potential targets and compounds for future therapies.


Overall, this update provided valuable insights into the ongoing research and development in Angelman Syndrome. The collaboration between researchers, clinicians, foundations, and patient advocacy groups is crucial in advancing the field and developing effective treatments. While there are still challenges to overcome, there is hope for significant progress in the coming years.

Talk details

  • Title: AS Research & Development Update, Part 2
  • Author(s): Dan Harvey, Matt During, Eugene Schneider, Jodi Cook
  • Author(s)’ affiliation: Dart NeuroScience; Ovid Therapeutics; Ionis Pharmaceutical; Agilis Biotherapeutics
  • Publication date: 2015-08-21
  • Collection: 2015 ASF Family Conference