Investigating that notion, Bear's team created mutant mice that lacked both the FMRP gene and had a 50 percent reduction in their production of mGluR5. They reduced rather than eliminated the activity of mGluR5, so that they could mimic what might happen if a drug treatment for fragile X was used in humans.
The mouse tests showed that the reduction in the mGluR5 gene could stop many of the abnormalities caused by the absence of FMRP. The double-mutant mice showed an improvement in their brain structure and function, in their brains' ability to make key proteins, as well as in memory and body growth.
Animals without the FMRP gene did produce an overgrowth of the spinal neurons called dendritic spines. However, the accompanying 50 percent reduction in mGluR5 allowed mice to maintain normal spine density.
In addition, the double mutant mice had substantial reductions in epileptic seizures, the researchers found.
Based on these results, human trials focused on mGluR5 should begin next year, Bear said. "I am cautiously optimistic that we will be able to correct some of the symptoms of the disease," he said.
One expert believes that mGluR5 could be a powerful target for correcting fragile X syndrome.
"This is a very important paper that demonstrates a remarkable rescue of fragile X features when the knockout mouse is crossed with a mGluR5-deficient mouse," said Dr. Randi Hagerman, a professor of pediatrics and medical director of the M.I.N.D. Institute at the University of California, Davis.
This is "wonderful" support for the therapeutic use of drugs known as mGluR5 antagonists in the treatment of fragile X syndrome, Hagerman said.
"Although there was good evidence for this treatment in the trial of mGluR5 antagonists in the knockout mouse [lacking FMRP] and other animal models of fragile X, th
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