Common Antibiotic Relieves Anxiety and Boosts Attention in Fragile X Syndrome PatientsA common antibiotic often prescribed to treat adolescent acne has been found to decrease anxiety and also increase attention spans and communication skills in patients with fragile X syndrome, according to a new survey study by the University of California-Davis MIND Institute.

Fragile X is the most commonly inherited type of mental impairment.  One third of all children with this syndrome will develop autism, and about five percent of children with an autism spectrum disorder have fragile X.   Fragile X is estimated to affect 1 in 3,600 males and 1 in 4,000 females.

The syndrome presents itself in a variety of disabilities, from learning disorders to mild to severe intellectual impairment (mental retardation) as well as in emotional and behavioral problems. It may also include certain physical characteristics, such as having larger ears or more flexible finger joints, with symptoms usually more severe in boys.

For the study, a total of 53 participants (three of these dropped out after a few days because of side effects), ranging in age from 4 months to 25 years,  took minocycline between two weeks and 20 months, with dosages of 25 to 200 milligrams per day.  Parents recorded their children’s overall responses to the drug.

After the participants were treated with minocycline for an average of three months, parents reported improvements in the children’s use of language, attention levels and behavior, all while having mostly mild side effects.  Results included the following:   Fifty-four percent reported improvements in language use, 50 percent reported an improvement in attention span, 44 percent reported an improvement in social communication and 30 percent reported a decrease in anxiety levels.   Most parents said their children experienced mild side effects, such as an upset stomach.

In anecdotal reports, some parents said their children were “becoming more conversational, articulate and talkative.” Parents also reported that their children were more focused and “had longer attention spans when playing, doing homework or participating in another activity.”

The team believes that the study is very promising. The results led to a placebo-controlled clinical trial of treating people with fragile X with minocycline, funded by the National Fragile X Foundation.

“This preliminary survey demonstrated improvements in participants, however, a controlled clinical trial is needed to compare the efficacy of treating patients with minocycline to treatment with a placebo,” said Randi Hagerman, Fragile X Endowed Chair, medical director of the UC-Davis MIND Institute and one of the world’s leading experts on fragile X syndrome.

Minocycline is one of the most commonly prescribed medications for adolescent acne and has been in use since the 1960s. The drug has been found to have neuroprotective actions and has been shown to improve neurodegenerative diseases like Parkinson’s and Huntington’s in animal studies.

Interest in its use in human patients with fragile X surged when a 2009 study reported that minocycline improved cognition in mice genetically engineered to have fragile X. That study’s senior author was Iryna M. Ethell of  the University of California-Riverside, who also is an author with Hagerman of the current research.

Ethell’s 2009 team discovered that minocycline lowers the levels of matrix metalloproteinase 9 (MMP9), an enzyme whose levels and activity are overabundant in the fragile X mouse. MMP9 inhibits development of dendritic spines, small mushroom-like projections at the ends of synapses that allow neural cells to communicate. Lowering the levels of MMP9 strengthens dendritic spines and improves communication circuits in the brain.

“It’s really exciting to see applications like this of our mouse-model research,” said Ethell.

The study was conducted in collaboration with lead author Agustini Utari, a fellow at the UC-Davis MIND Institute from the Center for Biomedical Research, Diponegoro University, Indonesia, where the prevalence of fragile X syndrome appears to be high.

“I am very excited about the opportunity to bring a study of minocycline and fragile X to Indonesia,” Utari said.

Other study authors include Weerasak Chonchaiya, Susan M. Rivera and Andrea Schneider of the UC-Davis MIND Institute; Sultana M.H. Faradz of the Center for Biomedical Research, Diponegoro University, Indonesia; and Danh V. Nguyen, Department of Public Health Sciences, UC-Davis.

“Minocycline Treatment in Patients with Fragile X Syndrome and Exploration of Outcome Measures” is published in the September 2010 issue of the American Journal of Intellectual and Developmental Disabilities.

UC Davis Mind Institute