Sonic the Hedgehog Reverses Down syndrome in Mice

Pictogram of headline

Last week, researchers reported reversing the effects of Down syndrome in the brains of genetically-engineered mice with a single injection. Already, the potential for future treatments based on this technique has been questioned. 

In a very helpful article, Robert Gonzalez writing at io9 breaks down the announcement that researchers had reversed Down syndrome in the genetically-engineered mice. The highlights:

• The mice have to be genetically-engineered to exhibit symptoms associated with Down syndrome because, for one fundamental reason, Down syndrome is caused in humans by a triplicate of the 21st Chromosome and mice only have 20 chromosomes.
• The mice are genetically-engineered with about half the genes over-expressed in Down syndrome.
• The injection of SAG, sonic hedgehog pathway agonis, activates the sonic hedgehog pathway.
• The sonic hedgehog pathway is critical for protein development. It gets its name from fruit flies that lack the protein growing spines like the SEGA video game character.
• The injection caused the cerebellum, typically smaller in the genetically-engineered mice, to grow to typical size with similar number of neurons.
• BUT, mice with the Down syndrome-type genes have a signalling problem in their cerebellum that was still present even in the mice treated with the SAG injection.
• The SAG-treated mice showed typical hippocampus development (another part of the brain) with positive results in learning and memory.
• BUT, no change was seen in the pre-frontal cortex, responsible for planning and decision-making.
• Lastly, while treatments typically begin in animal trials, people should remain cautious in expecting similar successes when those treatments are translated to human trials.

So, an injection in the brains of mice with some of the genes expressed in Down syndrome had mixed results and it is unknown if those results can be expected if humans received the same injection. But, a significant scientific development nonetheless in showing potential changes to brains. The full study is available at this link, but requires a subscription.

Tomorrow, general concerns about injecting SEGA video game character into the brain (with the most bizarre image yet to appear on this blog).