Mice get all the bum luck, don’t they? Not only do they live filthy little lives when they’re out in the open, but anytime somebody actually wants one, it’s either to feed a snake or to do medical experiments on it. (That’ll teach the little bastard not to get into my peanut butter sandwich while I’m eating it.) Researchers from Johns Hopkins and the National Institutes of Health have genetically engineered mice to pass on Down syndrome-like symptoms through their offspring. The good news is, they have also developed a compound that effectively cures their afflictions when injected into them on the same day as their birth.
The compound is called a “sonic hedgehog pathway agonist,” and it has nothing to do with Sega or Knuckles. “Most people with Down syndrome have a cerebellum that’s about 60 percent of the normal size,” says professor Roger Reeves, Ph.D., of the McKusick-Nathans Institute of Genetic Medicine at 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.” Because it was such a labor-intensive and time-consuming project, it would have been foolish to just accept these results as they were without testing how else the mice were affected.
The initial test mice, who were modified to have duplicates of half of the genes whose mutations are responsible for Down’s in humans, had been placed in a water maze to see how quickly they could remember how to navigate their way to a platform. When other modified mice were born, they were injected with the compound as their brains were still growing. Once they were far enough along, these mice were then given the water maze test, and the scientists were shocked to find that they were just as successful as the normal mice in remembering their way around the maze.
“What we didn’t expect were the effects on learning and memory, which are generally controlled by the hippocampus, not the cerebellum.” While more work will need to be done to figure out why the treatment is effective in this way. It’s thought that perhaps the communication between these two areas of the brain is strengthened by this procedure, but time will tell.
Unfortunately, much like the genetically modified mice with extended lifespans, there is no plan to try this treatment on humans for quite a while. It isn’t clear how the agonist would change human brain growth, and there is always the chance that it could cause mutations in other areas, resulting in cancer. Now the focus becomes keeping the injection’s activity within the cerebellum itself.
“Down syndrome is very complex,” Reeves says, “and nobody thinks there’s going to be a silver bullet that normalizes cognition. Multiple approaches will be needed.” And if it’s anything like other medical advancements of late, 3D printing and stem cells will be involved.