Fragile X Syndrome Fenobam Drug Evaluation

Author: Rush University Medical Center
Published: 7 Jan 2009 - Updated: 1 Nov 2026

Table of Contents:
Synopsis - Definition - Overview - Related Content

Synopsis

Findings by researchers could lead to a new drug for treating Fragile X Syndrome inherited disorder.

Topic Definition

Fragile X Syndrome

Fragile X Syndrome is defined as a genetically inherited form of mental retardation. The syndrome occurs when there is a change or mutation in a single gene, referred to as the 'Fragile X Mental Retardation 1 (FMR1) Gene.' The gene usually produces a protein a person's body requires for their body to develop; however, when there is a change in this gene, the person's body has only a tiny amount of the protein or none of it. This can cause symptoms of Fragile X. Fragile X may be passed from a parent to a child. Parents may have children with the syndrome, even if the parents themselves do not have the syndrome.

Overview

Initial findings by researchers at Rush University Medical Center and the University of California, Davis, could lead to a new approach for treating Fragile X Syndrome inherited disorder.

A pilot trial of an oral drug therapy called fenobam has shown promising initial results. It could be a potential new treatment option for adult patients with Fragile X syndrome (FXS). Findings of the open-label, single-dose study by researchers at Rush University Medical Center and the University of California, Davis, Medical Center are to be published in the January issue of the Journal of Medical Genetics.

Results of an initial evaluation of the safety of fenobam, a mGluR5 antagonist, in adult males and females with Fragile X syndrome showed no adverse side effects from the medication.

"This is the first study assessing the safety and pharmacokinetic metabolism of a mGluR5 antagonist in humans with Fragile X syndrome," said Dr. Elizabeth Berry-Kravis, a pediatric neurologist at Rush and principal investigator of the study. "Also, some patients showed calmed behavior and rapid reduction in hyperactivity and anxiety, similar to effects of the drug in mouse models."

Fragile X syndrome is the most common inherited cause of mental impairment and the most common known cause of autism. Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and ethnic groups (source: Centers for Disease Control (CDC)). About 1 in 259 women carry fragile X and could pass it to their children. About 1 in 800 men carry fragile X; their daughters will also be carriers. Symptoms of Fragile X syndrome include mental impairment such as learning disabilities, attention deficit, hyperactivity, autistic-like behaviors, and anxiety and unstable mood.

Fragile X syndrome is caused by a lack of activity of the FMR1 gene, which is responsible for a protein called FMRP. Without FMRP, activation of cell pathways by a brain receptor protein called mGluR5 goes unchecked, and it has been theorized that this plays an important part in Fragile X syndrome.

To test this theory, past researchers have used laboratory mice without an active FMR1 gene, like in Fragile X syndrome, but with a reduced amount of mGluR5 protein. The mice improved their brain structure and function, their brains' ability to make key proteins, and memory and body growth. This shows that the over-activation of mGluR5 is very important in Fragile X syndrome and suggests a path for drug development to treat the syndrome.

In the current study, twelve participants recruited by Rush and the University of California, Davis, received a single oral dose of 50-to-150 mg of fenobam. Prepulse inhibition (PPI) and continuous performance test (CPT) were obtained before and after dosing to explore the effects of fenobam on sensory gating, attention, and inhibition measures. In six of the 12 individuals, there was a 20 percent improvement.

"Currently, there are no therapies on the market to treat cognitive deficits associated with Fragile X syndrome," said Berry-Kravis. "This pilot study has identified the potential beneficial clinical effects of fenobam, but further research is needed."

References

The Fragile X Syndrome clinic at Rush is dedicated to the care of children with Fragile X syndrome, an X-chromosome-linked condition that is the most common inherited cause of mental retardation. The clinic is the only one of its kind in Chicago and among a few in the Midwest. The fragile X clinic at Rush was started in 1991 to serve the unique needs of the fragile X population. The clinic maintains affiliations with specialists in pediatrics, neurology, genetics, optometry, child psychology, special education/education psychology, speech and language, occupational therapy, and dentistry who have experience working with individuals with fragile X syndrome.

Related Information

• Study Shows Promise for New Drug to Treat Fragile X
• Defining Fragile X Syndrome
• Could Fragile X Be Key to Autism Puzzle?
• Fragile X Syndrome: Genetic Clues Found
• Fragile X Study Provides Hope for Autism Treatment
• New Registry to Accelerate Research on Fragile X Syndrome

Attribution/Source(s): This quality-reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally issued as a press release by Rush University Medical Center and published on 7 Jan 2009. Last updated on 1 Nov 2026. This content may have been edited for style, clarity, or brevity.