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Down syndrome reversed in newborn mice with single injection

Down syndrome reversed in newborn mice with single injection 1

US researchers have found a way to reverse Down syndrome in newborn lab mice by injecting an experimental compound that causes the brain to grow normally.

The study, published in the Science Translational Medicine journal, offers no direct link to a treatment for humans but scientists are hopeful it may offer a path towards future breakthroughs.

There is no cure for Down syndrome, which is caused by the presence of an additional chromosome and results in intellectual disabilities, distinctive facial features and other health problems.

The team at Johns Hopkins University of Medicine, in Baltimore, used lab mice that were genetically engineered to have extra copies of about half the genes found on human chromosome 21, leading to Down syndrome-like conditions such as smaller brains and difficulty learning to navigate a maze.

On the day the mice were born, scientists injected them with a small molecule known as a sonic hedgehog pathway agonist.

‘Unexpected benefits’ in learning and memory

The compound, which has not been proven safe for use in humans, is designed to boost normal growth of the brain and body via a gene known as SHH.

The gene provides instructions for making a protein called sonic hedgehog, which is essential for development.

We were able to completely normalize growth of the cerebellum through adulthood with that single injection

Roger Reeves, Johns Hopkins University School of Medicine

“It worked beautifully,” said Roger Reeves of the Johns Hopkins University School of Medicine.

“Most people with Down syndrome have a cerebellum that’s about 60 per cent of the normal size,” he said.

“We were able to completely normalise growth of the cerebellum through adulthood with that single injection.”

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The injection also led to unexpected benefits in learning and memory, normally handled by a different part of the brain known as the hippocampus.

Researchers found that the treated mice did as well as normal mice on a test of locating a water platform while in a swimming maze.

However, adjusting the treatment for human use would be complicated, since altering the growth of the brain could lead to unintended consequences, such as triggering cancer.

“Down syndrome is very complex and nobody thinks there’s going to be a silver bullet that normalises cognition,” Dr Reeves said.

“Multiple approaches will be needed.”

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