Brain Defect Helps Drive Fragile X Syndrome
THURSDAY, Sept. 20 -- A newly discovered brain defect might be a target for the treatment of the inherited mental disorder known as fragile X syndrome, researchers report.
The discovery in rats provides an understanding of how the gene mutation responsible for the condition changes the way brain cells communicate, according to the report in this week's issue of the Proceedings of the National Academy of Sciences.
"Fragile X syndrome is the most common form of inherited mental retardation," explained co-author Gary J. Bassell, a professor of cell biology at Emory University in Atlanta. "It has strong links to autism and epilepsy."
Fragile X syndrome occurs in approximately one in 4,000 males and one in 8,000 females, Bassell noted.
Working with rat brain cells, the team found that synapses between brain cells in the part of the brain called the hippocampus are defective in animals with fragile X, Bassell said.
"We discovered what the specific underlying defect is," he said. "It is actually a defect in the mGluR5 receptor, which is on the surface of neurons. The defect is that there is excessive signaling."
Children with fragile X have difficulty in processing information, because these receptors allow too much signaling and change the function of other receptors, Bassell theorized.
When his team treated the receptor with an mGluR5 antagonist called MPEP, they were able to reverse the effects of the mutation. "When you quiet down this receptor, it corrects the defects that occur in other receptors as well," he noted.
Bassell stressed that MPEP is not a suitable drug for humans. However, the discovery should help researchers find other drugs that do the same thing safely.
Any drug that targets the receptor will not be a cure for fragile X, Bassell cautioned. "These children have a permanent defect in their DNA," he said. "The goal here is to improve the quality of life for these children. We are going to decrease the severity of episodes to help them focus better on learning tasks and help with the behavior problems and improve their cognitive function," he said.
One expert hailed the finding.
"This is a very important paper," said Dr. Randi Hagerman, a professor of pediatrics and medical director of the M.I.N.D. Institute at the University of California, Davis. "It proves that mGluR5 antagonists will be helpful in kids with fragile X syndrome," she added. "We are looking forward to a new age of treatment in fragile X syndrome."
Hagerman noted that trials with mGluR5 antagonists on adults with fragile X syndrome will be starting this fall. "If things go well with adults, then we will move to pediatric trials," she said.
"This is a very hopeful message," Hagerman said. "This means that there will be very specific treatments that will have an impact in the very near future."
Another expert agreed that the discovery should lead to new treatments for children with fragile X.
"This is a very exciting paper, which is a powerful confirmation of the mGluR theory of fragile X," said Dr. Michael Tranfaglia, medical director of the FRAXA Research Foundation. "Since FRAXA Research Foundation is currently working with several pharmaceutical companies to bring mGluR5 antagonists into clinical trials for fragile X, we are delighted to see this elegant proof of the therapeutic potential of this class of drugs."
For more information on fragile X syndrome, visit the Fragile X Research Foundation.
Posted: September 2007