A team of researchers including an India scientist have considerably reduced a wide range of abnormalities due to fragile X syndrome in mice by altering only a single gene.
Fragile X syndrome is known to be caused by loss of the gene for "fragile X mental retardation protein" (FMRP), which is believed to act as a brake on protein synthesis in specific areas of brain circuitry.
The study was conducted by a group of international researchers including Shankaranarayana Rao, B.S., Department of Neurophysiology, National Institute of Mental Health and Neuroscience, Bangalore, India.
The researchers said that their achievement offers the potential for treatment of the disorder, the most common form of inherited mental retardation and a leading identified genetic cause of autism.
Currently, there is no treatment or therapy for fragile X syndrome, whose symptoms include mental retardation, epilepsy, and abnormal body growth.
The researchers' idea was that loss of the 'brake' would allow another protein that stimulates this process, called metabotropic glutamate receptor 5 (mGluR5), to function unchecked.
In their study, in order to test the idea, they studied mice that produce many of the characteristic pathologies of fragile X in humans due to a loss of the FMRP gene.
Though, the critical test was when they also created double mutant mice that lacked both the FMRP gene and had a 50 percent reduction in mGluR5.
They chose only to reduce the activity of the metabotropic glutamate receptor gene, rather than eliminate it, in order to reflect what might be achieved using drug treatment for fragile X in humans.
The scientists' tests on the double mutant mice revealed that the mGluR5 gene reduction greatly alleviated many abnormalities produced by loss of FMRP. The double mutant mice showed a rescue of abnormalities in brain structure and function, brain protein synthesis, memory, and body growth.
For example, loss of the FMRP gene produces overgrowth of the connections among neurons called dendritic spines. However, the additional 50 percent reduction in mGluR5 gene produced mice with completely normal spine density.
The scientists found that the double mutants showed substantial reduction in epileptic seizures caused by lack of FMRP.
They concluded that "it is remarkable that by reducing mGluR5 gene dosage by 50 percent, we were able to bring multiple, widely varied fragile X phenotypes significantly closer to normal."
They also concluded that "these findings have major therapeutic implications for fragile X syndrome and autism."
The study is published in the journal Neuron.