The First Clinical Evidence that the Drug Mavoglurant Improves Responsiveness in Fragile X Syndrome (FXS)

Results of a study reported in PLOS ONE that was conducted by a team of scientists indicate that the experimental drug mavoglurant improves responsiveness and eye gaze for patients with the rare disorder fragile X syndrome.

About the Fragile X Syndrome (FXS)

Fragile X Syndrome is an X chromosome-linked genetic condition and it is characterized by symptoms which range from mental disabilities to epilepsy and autism.  It is one of the most common forms of inherited intellectual disability. Additionally, it affects physical features and creates high rates of anxiety and social withdrawal, inattention, impulsivity, hyperactivity, aggression, and self-injury.

According to an article by Regina Dahlhaus of the Institute of Biochemistry, University of Erlangen-Nuremberg, Germany, FXS is caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1. FXS occurs in approximately one in 4,000 males and one in 8,000 females.

About the Study

Aided by an infrared binocular eye tracker, and prior to the onset of the blind study, the researchers collected data of gaze patterns from fifty-seven FXS patients between the ages of 12 and 45 with IQs below 70. Gaze avoidance is a characteristic of FXS. Patients also show greater response to the emotions displayed by others.

This phase was followed by three months of treatment where a group of patients received mavoglurant at either 25 mg., 50 mg., or 100 mg. doses, which was compared alongside a placebo group.

Results of the Study

The researchers discovered that mavoglurant, known as a mGluR5 negative modulator, could be a promising drug and it may impact a core behavioral feature in people with fragile X syndrome (FXS).

The study shows patients had improvements in pupil dilation. This is a positive sign of response to faces and it occurred post mavoglurant treatment as opposed to the preclinical baseline and to the placebo.

David Hessl, clinical professor in the Department of Psychiatry and Behavioral Sciences and a researcher at the MIND Institute, emphasizes the importance of the study results since the larger trials did not show any drug benefit over a placebo.

“These objective indicators serve as biomarkers that appear to be sensitive to the treatment.” – Dr. David Hessl

Hessl believes that researchers will see the possibility that mGluR will still be an effective therapeutic target for individuals with FXS. He hopes that these clinical results may encourage researchers to examine other trial designs.

Dr. Elizabeth Berry-Kravis, a pediatric neurologist at Rush University Medical Center and senior author of the study, reports that drugs in the same category as mavoglurant have produced improvements in over 40 scientific papers on the fragile X mouse, rat and fly models.  However, until now, the findings have not been understood in relation to human trials.

Future FXS Trials

A study led by Berry-Kravis to evaluate mavoglurant’s effect on language learning in three to six-year-olds with FXS is currently underway.  This large-scale clinical trial of Novartis AFQ056 (a mGluR5 antagonist) is provided through the NeuroNext network and is funded by the National Institute of Health. One of the goals of the study is to change the development process of drugs designed for Fragile X and for developmental disabilities in general.

Berry-Kravis comments that the eye tracking data gives support to the NeuroNext study by evaluating the effect of the drug on learning in children who have a greater potential for seeing improvements compared to older age groups.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

Share this post

Share on facebook
Share on twitter
Share on linkedin
Share on pinterest
Share on print
Share on email