WASHINGTON (Reuters) - Researchers said they have partially reversed in mice a common cause of autism and mental retardation, and said it might be possible to design a drug that would do the same thing for people.
They found that by blocking a normal enzyme, they could reverse some of the brain abnormalities associated with the inherited condition, called Fragile X Syndrome, and correct some of the symptoms in the mice.
“This is the first case where the reversal of Fragile X Syndrome (has been) demonstrated in the animal model, not only at the level of behavior but also in the underlying cellular mechanisms,” said Susumu Tonegawa, a senior neuroscientist at the Massachusetts Institute of Technology who led the research.
Fragile X Syndrome is the most common hereditary cause of mental retardation and autism. The one in 4,000 boys and one in 6,000 girls who are affected often have developmental delays and hyperactivity, and engage in aimless, repetitive behaviors.
It is caused by a mutated gene on the X chromosome that affects dendritic spines — the long, thin structures that allow brain cells to communicate with each other. They become too numerous, as well as too long and thin, weakening these electrical signals.
“This has been thought to be the major underlying reason why these patients show behavioral abnormalities,” said Tonegawa, who worked with researchers in India and South Korea.
The researchers noticed that when they blocked the action of another nerve cell-shaping enzyme called P21-activated kinase, or PAK, in the brains of otherwise normal mice, they could produce the opposite effect: the dendritic spines in these mice were short and thick, and fewer were formed.
The mice also had abnormally low levels of electrical signaling, according to the report, published in this week’s issue of the Proceedings of the National Academy of Sciences.
So the scientists bred mice with both the Fragile X gene mutation and a version of PAK that was programmed to fail.
This inactive form of PAK only kicked in a month after the mice were born. And once it did, the researchers found that symptoms of Fragile X, which include excessive movement and difficulty completing memory tasks, were greatly reduced in the mice.
When they looked at their brains, the dendritic spines looked fairly normal.
While such genetic manipulation would be difficult to recreate in human children, a chemical compound that can directly inhibit the protein may make an effective drug, Tonegawa said.