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Experimental treatment reverses Down syndrome in lab mice

Posted on September 5, 2013

WASHINGTON, (PNA/Xinhua) — U.S. researchers said Wednesday that they have identified a compound that appears to reverse the learning deficits associated with Down syndrome in lab mice.

While use of the compound, a small molecule known as a sonic hedgehog pathway agonist, has not been proven safe to try in people with Down syndrome, the researchers said their experiments hold promise for developing drugs like it.

Down syndrome is one of the most common chromosomal abnormalities in children, and a leading cause of intellectual disability. It occurs when people have three, rather than the usual two, copies of chromosome 21. As a result of this “trisomy,” people with Down syndrome have extra copies of more than 300 genes, leading to intellectual disabilities, distinctive facial features and sometimes heart problems and other health effects.

In their study, researchers from the Johns Hopkins University and the U.S. National Institutes of Health genetically modified mice to give them extra copies of about half of the genes found on human chromosome 21, leading to similar characteristics to humans with Down syndrome, including relatively small cerebellums and difficulty in learning and remembering how to navigate through a familiar space.

The researchers injected the mice the compound right after their birth and found that single injection enabled the cerebellum of the rodents’ brains to grow to a normal size.

“Most people with Down syndrome have a cerebellum that’s about 60 percent of the normal size,” said lead author Roger Reeves of the Johns Hopkins University School of Medicine.

“We treated the Down syndrome-like mice with a compound we thought might normalize the cerebellum’s growth, and it worked beautifully,” Reeves said.

“What we didn’t expect were the effects on learning and memory, which are generally controlled by the hippocampus, not the cerebellum,” he said.

The team tested the treated mice against untreated Down syndrome-like mice and normal mice in a variety of ways, and found that the treated mice did just as well as the normal ones on a test of locating a platform while swimming in a so-called water maze.

Further research, however, is needed to know why exactly the treatment works and if it can be altered for human use, the researchers wrote in the journal Science Translational Medicine.

“Down syndrome is very complex, and nobody thinks there’s going to be a silver bullet that normalizes cognition,” Reeves said. ” Multiple approaches will be needed.”

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