Fragile X is linked to over-activity in the brain

There is currently no treatment for fragile X syndrome, also linked to epilepsy and abnormal body growth, but the new work raises hopes of progress.

A Massachusetts team were able to trigger big improvements in mice by tweaking just one gene.

The results of the study are published in the journal Neuron.

These findings have major therapeutic implications for fragile X syndrome and autism

Dr Mark Bear

Picower Institute for Learning and Memory

Fragile X is caused by the loss of a gene called FMRP which produces a protein which acts as a brake on protein synthesis in specific areas of brain circuitry.

The theory is that this allows another protein - mGluR5 - which stimulates this process to function unchecked, resulting in over-activity in the brain.

The researchers, from the Picower Institute for Learning and Memory at Massachusetts Institute of Technology, examined mice which lack the FMRP gene, and show many of the symptoms associated with fragile X.

They also created mice that not only lacked FMRP, but also had a 50% reduction in mGluR5.

Fewer abnormalities

This second group of mice showed fewer symptoms of fragile X, fewer signs of abnormalities in the brain, and fewer signs of abnormal body growth.

FRAGILE X SYNDROME Boys usually more severely affected Main problem is mental impairment Other symptoms include hyperactivity, attention deficit disorder, emotional and behavioural problems, anxiety and mood swings There may also be characteristic facial features, such as a long face and large ears Other physical features include flat feet and hyperextensible joints

For example, loss of the FMRP gene produces overgrowth of connections between nerve cells called dendritic spines.

However, when coupled with a 50% reduction in mGluR5, spine density was completely normal.

The 'double mutant' mice also showed substantial reduction in epileptic seizures.

Lead researcher Dr Mark Bear said: "These findings have major therapeutic implications for fragile X syndrome and autism."

Dr Mark Hirst, scientific adviser to UK Fragile X Society, said: "Whilst we know that many proteins are regulated by the fragile X protein, and are therefore disrupted in fragile X individuals, mGluR5 seems to be one of the most important."

However, he stressed that the mice in the study had benefited from reduced levels of mGluR5 throughout their development - something it would be not be able to replicate in a human drug treatment.

He added: "We must not take our eye off the other proteins that are mis-regulated, as the basis of fragile X syndrome is likely to be more complex and involve other pathways."