Project Description

Study Title:  A Monocentric, Prospective, Longitudinal and Observational Natural History Study for patients with Angelman Syndrome in the United Kingdom: NatHis – FAST UK

Chief Investigator: Professor Laurent Servais

Sponsor: University of Oxford

Funders: Foundation for Angelman Syndrome Therapeutics (FAST) UK F. Hoffmann-La Roche Ltd

More than 20 compounds from more than 13 companies and institutions are currently in the pipeline of Angelman Syndrome (AS) therapeutics, with some of them already at clinical trial stage. Nevertheless, clinical trial readiness is still largely immature; this study aims to prepare the NHS for upcoming clinical trials and help the healthcare community to obtain a better understanding of AS and its natural history.

The proposed research study is a four-year natural history study for AS patients in the United Kingdom (UK); more specifically, this includes: six to eight months of recruitment, two years of follow-up, and one year of data analysis. We plan to include 40 participants of different ages and genetic backgrounds and to follow-up with each participant every six months for two years.

We plan to obtain a holistic view of AS by collecting retrospective and prospective relevant clinical data, by using scales and questionnaires for the assessment of motor function and global development based on age, as well as by collecting sleep and seizure diaries. Via proteomic analysis and EEG recordings, we will try to identify biomarkers associated with disease outcome. We will attempt to get a better understanding of the disease burden for families and patients, as well as of the associated healthcare cost. In addition, we plan to collect real-life motor function data using a watch-like device for continuous monitoring of movement and to validate objective outcome measures that can act as endpoints in future clinical trials. We previously showed that collecting these data are feasible for AS patients in an uncontrolled environment, and we identified quantifiable parameters (e.g. number of falls, walking perimeter, or stride regularity) that are very different to those of age-matched controls.

We aim to connect with experienced research centres around the world working with biomarkers, EEG data, outcome measures and clinical scales for AS patients.  The ultimate aim of this study is to alter the culture in the conduct of clinical trials and to contribute to the design of clinical trials that help specialists make safer and quicker clinical decisions on the efficacy of treatments for AS patients.