Ganaxolone Fragile X Clinical Trial Showed Disappointing Results

Dr. Randi Hagerman, at the University of California at Davis, along with Dr. Frank Kooy and Dr. Anke Van Dijck of Antwerp University, completed a phase 2 trial of the drug ganaxolone to treat Fragile X syndrome in children.

The trial enrolled 59 participants between 6 – 17 years old exhibiting a diverse range and severity of symptoms. The study did not show overall significant changes on the primary or secondary scales chosen to measure behavior. While one rating measure did suggest that children with particularly high anxiety levels experienced significant improvements in anxiety, attention, and hyperactivity, another rating scale did not.

Ganaxolone showed no serious side effects in the study. The most commonly reported side effects were sleepiness, fatigue, and dizziness. However, most participants recovered before the end of the trial.

The Ganaxolone Study Design

The study enrolled 59 children at two sites: the University of California at Davis, under the direction of Dr. Randi Hagerman, and at Antwerp University, Belgium, under the direction of Dr. Kooy and Dr. Van Dijck. Participants were randomly assigned to one of two conditions: one group first received placebo and then ganaxolone; and the other group received ganaxolone first, followed by placebo. Each treatment was administered for 4 weeks (3 weeks in Belgium) with 2 weeks in between to serve as a washout period.

How Ganaxolone Works

In the brain, excitatory neurons and inhibitory neurons work together to balance emotions and behaviors. In FXS, there is an excess of mGluR activity, which excites the brain, and a dysfunction of its counterpart GABA, which should be balancing this excitement. This overstimulation is believed to be the cause of many behaviors associated with FXS, including anxiety, attention deficits, and hyperactivity. Ganaxolone mimics a brain chemical which makes GABA receptors more receptive, increasing the effects of GABA already present in the central nervous system and therefore balancing neuron activity.

Ganaxolone has Limited Potential as a Treatment for Fragile X

Although the trial employed a range of rating scales to measure many aspects of FXS-associated behavior, researchers did not find significant improvements on any of the scales. The only significant results in this study were found in post hoc analysis, and not in any of the scales chosen for the trial. The study suggests that, in general, ganaxolone is not an effective treatment for FXS. While this is disappointing, it does offer useful guidance for families confronted with dozens of potential medications addressing various symptoms of Fragile X. Unfortunately that is how research works – if every drug brought a good result these trials wouldn’t be needed.

However, ganaxolone might have potential for several subgroups of FXS children. One rating measure suggested that children with particularly high anxiety levels experienced improvements in anxiety, attention, and hyperactivity. Similar results were found in children with low IQs. Ganaxolone may also provide other benefits, as it has shown positive effects in reducing seizures in children, a common symptom of FXS. It has been shown to be a safe medication for young children.

Researchers concluded that more research is warranted in ganaxolone to treat children with FXS, and this research has provided useful insights into the subgroups that may be most responsive.

Published Paper

J Neurodev Disord. 2017 Aug 2;9(1):26. doi: 10.1186/s11689-017-9207-8.
A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with Fragile X syndrome.
Ligsay A 1,2, Van Dijck A 3,4, Nguyen DV 5,6, Lozano R 1,7,8, Chen Y 6, Bickel ES 1,8, Hessl D 1,9, Schneider A 1,8, Angkustsiri K 1,8, Tassone F 1,10, Ceulemans B 4, Kooy RF 3, Hagerman RJ 11,12.


Explore Current Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.

Share via
Copy link