Levodopa in Angelman Syndrome: Results of a Multicenter Randomized Controlled Trial
A multicentre randomised controlled trial was conducted to assess the effects of Levodopa in patients with Angelman Syndrome. The trial was conducted over several years and involved a large team of researchers. The study found that Levodopa is relatively safe, with no significant difference in side effects between the placebo and Levodopa groups. However, there was no statistically significant improvement in developmental outcomes in the Levodopa group. There was some indication of improvement in stereotypy and irritability in the Levodopa group, but no change in hyperactivity. The researchers concluded that based on their data, they would not recommend the use of Levodopa for Angelman Syndrome.
This talk discusses the results of a multicenter randomized controlled trial on the use of Levodopa in Angelman Syndrome. The trial was conducted a few years ago and involved a large team of dedicated professionals. The trial was initiated within a consortium formed as part of the NIH Rare Diseases Clinical Research Network.
The trial began in the early days of 2010-2011, building on the infrastructure already in place from previous studies. The trial started with a natural history study, which revealed significant phenotypic differences across various brain-driven subgroups. This data highlighted the need to consider subgroups when conducting clinical trials.
Previous Clinical Trials
Before embarking on the Levodopa trial, two previous clinical trials had been conducted within the consortium on Angelman syndrome. The first study showed no difference and the second study, despite involving a larger number of patients, also showed no clinical effect.
The Scientific Basis of the Trial
The scientific basis of the trial built upon Ed Weeber’s groundbreaking work published in 2007. He showed that excessive phosphorylation of a molecule called CAM kinase 2 in neurons could impact learning. This discovery provided a potential drug-able target for the first time.
The Levodopa Trial
The question raised was whether giving Levodopa to children with Angelman syndrome could reduce some of the excessive phosphorylation in CAM kinase 2, thereby rescuing the phenotype and improving development. The trial was conducted in a controlled setting to answer this question.
Results of the Trial
The trial took more than two and a half years to recruit 78 participants between the ages of four and 13. The results showed that Levodopa is relatively safe, but there was no statistically significant difference in developmental outcomes over the course of a year. However, there seemed to be some improvement in stereotypy and irritability in the Levodopa group compared to the placebo group.
Based on the data, the use of Levodopa would not be recommended. However, the trial highlighted the importance of having a placebo group and the need for better and more sensitive developmental measures. The trial also underscored the challenges of conducting clinical trials in rare diseases.
- Title: Levodopa in Angelman Syndrome: Results of a Multicenter Randomized Controlled Trial
- Author(s): Wen-Han Tann
- Author(s)’ affiliation: Boston’s Children Hospital
- Publication date: 2017-01-17
- Collection: 2016 ASF-Dup15q Scientific Symposium