Potential new targeted treatment improves language, cognition, parents say
One of the antibiotics most commonly prescribed to treat adolescent acne can increase attention spans and communication and decrease anxiety in patients with fragile X syndrome, the most common inherited cause of mental impairment, according to a new survey study that is the first published on parents' reports of their children's responses to treatment with the medication.
Led by researchers at the UC Davis MIND Institute, the study examined parents' observations of their children's responses to minocycline - not the efficacy of treating patients with the drug. However, the researchers said that the study results are extremely promising. They led to a placebo-controlled clinical trial of treating people with fragile X with minocycline, funded by the National Fragile X Foundation.
"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. In the study, parents relate that after being treated for an average of three months, their children showed improvements in their use of language, attention levels and behavior, while experiencing mostly mild side effects.
"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.
Fragile X syndrome is a genetic disorder, the result of a defect on the X chromosome. It is estimated to affect 1 in 3,600 males and 1 in 4,000 females. One-third of all children with fragile X syndrome develop autism and approximately 5 percent of children with an autism-spectrum disorder have fragile X.
The condition causes a range of disabilities, from learning disorders to mild-to-severe intellectual impairment (mental retardation) and behavioral and emotional problems. It also is associated with certain physical characteristics, including prominent ears and flexible finger joints. The symptoms typically are more severe in boys than in girls.
Minocycline is one of the most commonly prescribed medications for adolescent acne and has been in use since its introduction in the 1960s. The drug also has been found to have neuroprotective qualities and in animal models improves neurodegenerative diseases like Parkinson's and Huntington's. Interest in its use in human patients with fragile X surged after a 2009 study found that minocycline improved cognition in mice genetically engineered to have fragile X. That study's senior author was Iryna M. Ethell of UC Riverside, who also is an author with Hagerman of the current research.
Ethell and her colleagues in 2009 found that minocycline lowers the levels of matrix metalloproteinase 9 (MMP9), an enzyme present in the normal brain whose levels and activity are over-expressed in the fragile X mouse. MMP9 inhibits development of structures called dendritic spines, tiny mushroom-like projections at the ends of synapses that allow neural cells to communicate. Lowering the amount and activity of MMP9 strengthens the dendritic spines and improves the establishment and maintenance of circuits in the brain.
"It's really exciting to see applications like this of our mouse-model research," Ethell said.