Intresting article

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Intresting article about autsim symtoms being reversed in mice.

http://news./s/afp/20070627/hl_afp/ushealthautism

CHICAGO (AFP) - US researchers have reversed the symptoms of mental

retardation and autism in mice by inhibiting an enzyme that affects

the connections between brain cells, researchers said Wednesday.

In a series of experiments on mice, the MIT investigators showed that

they could undo the brain damage seen in a condition called Fragile X

syndrome by inhibiting a key brain chemical called PAK.

In humans, Fragile X syndrome (FXS) is the leading cause of mental

retardation and the most common genetic cause of autism -- the

complex and devastating developmental disorder that is now being

diagnosed in increasing numbers of children.

The study raises the intriguing possibility that the brain damage

seen in children with the condition can be rolled back and identifies

a specific target for potential drug therapies.

" It opens up a new avenue for drug research to treat this condition, "

said Susumu Tonegawa, a neuroscientist at the Massachusetts Institute

of Technology in Cambridge, Massachusetts, and lead author of the

paper.

MIT researchers began by creating a batch of mice that had been

genetically modified to have Fragile X, a condition in which the

neurons of the brain are structurally abnormal and functionally

impaired compared to regular nerve cells.

These transgenic mice had many of the behavioral problems seen in

kids with the condition: hyperactivity, attention deficits,

repetitive behaviors and poor social skills.

The investigators then cross-bred these mice with another batch of

mice that had been genetically modified to inhibit the activity of

the PAK (p21-activated kinase) enzyme which is instrumental in

shaping the formation of neuronal connections in the brain.

The researchers knew that when PAK was inactivated, the mice

developed neurons that had short, fat dendritic spines, with a higher-

than-usual capacity for relaying the electrical impulses that pass

between brain cells.

In other words, the shape and function of the dendritic spines in the

PAK mice was just the reverse of those seen in the brain cells of the

mice with Fragile X syndrome.

The researchers gambled that the two abnormalities would cancel each

other out, and that's exactly what the experiment showed.

The cross-bred mice had been genetically engineered so that the

inactivation of the PAK enzyme began two weeks into the mouse's life

cycle, which in human terms would be several years after birth.

Tests and autopsies showed that the PAK-blocking action restored

electrical communication between neurons in the brains of the double

mutant mice, correcting their behavioral abnormalities in the process.

" This is very exciting because it suggests that PAK inhibitors could

be used for therapeutic purposes to reverse already established

mental impairments in fragile X children, " said Klann, a

professor at New York University's Center for Neural Science.

The study was conducted by Tonegawa and a postdoctoral student at

MIT's Picower Institute for Learning and Memory and appears in this

week's edition of the Proceedings of the National Academy of Sciences.