An estimated one in every 800 babies is born with Down syndrome in the United States, according to huffingtonpost.com, and now scientists are one step closer to finding a cure. It is still a long way off before we will be capable of preventing Down syndrome in humans, but scientists have found a way to stop some of the effects of the genetic disorder in affected mice.
Down syndrome in humans is a condition in which the individual has three copies of chromosome 21 instead of the typical two, according to sciencedaily.com. Some of the effects include intellectual disabilities, distinctive facial features, potential heart problems and sleep apnea. The negative physical afflictions decrease quality of life, and attempting to find a cure to prevent Down syndrome would be a great thing for future generations.
One of the scientists behind the research, a professor at Johns Hopkins University in Baltimore, Dr. Robert H. Reeves said, “Most people with Down syndrome have a cerebellum that’s about 60 percent of the normal size.” The same was seen in the genetically engineered Down syndrome-like mice. In the experiment, the mice were genetically engineered to have Down syndrome, which meant they had about half of the extra genes on human chromosome 21, according to ABC News, and this led to a brain size much smaller than their normal counterparts. The affected mice also had difficulty navigating through a maze and showed little sign of remembering the maze after having gone through it before.
In an attempt to cure the mice of their Down syndrome, on the day of their birth they were injected with a single-dose treatment which “appear[ed] to enable the cerebellum of the rodents’ brains to grow to a normal size,” according to Johns Hopkins Medicine. The organic molecule that is injected into the mice is known as a Sonic Hedgehog pathway agonist and is “designed to boost normal growth of the brain and body via the gene known as Sonic Hedgehog (SHH),” according to ABC News.
The organic molecule was injected on the day of their birth because the cerebellum was still developing, so the drug does not cure an already developed Down syndrome cerebellum but appears to promote healthy growth when the cerebellum is still in its developmental stage.
“We were able to completely normalize growth of the cerebellum through adulthood with that single injection,” Reeves said, according to the Huffington Post.
It is not exactly a complete cure for Down syndrome in mice, but it did in fact make the cerebellum grow to correct size instead of the 60 percent size normally seen in the cerebellum of Down syndrome individuals. These experiments on mice will hopefully help scientists one day create a similar treatment for humans.
The experiment also had promising results which the scientists did not anticipate.
“What we didn’t expect were the effects on learning and memory, which are generally controlled by the hippocampus, not the cerebellum,” Reeves said, according to Johns Hopkins Medicine. It was also observed that after being treated, the mice performed as well as normal mice on the maze tests, according to ABC News.
The extra chromosome 21 has more than three hundred genes coded on it, which makes it particularly difficult to cure Down syndrome. “Since the condition involves so many genes, developing treatments for it is a formidable challenge,” Reeves said.
Scientists are hesitant to make larger strides for a human cure because of all the unknown factors. They cannot even fully understand the reason behind the success of this experiment. The hippocampus was not expected to be affected in the way that it was. The examination of the cells in the hippocampus appeared unchanged, although they did in fact improve learning and memory in the mice, typically associated with the hippocampus. This is part of the reason that Reeves says much further research is needed to learn why the treatment works, according to Johns Hopkins Medicine.
According to ABC News, “Adjusting the treatment for human use would be complicated, since altering the growth of the brain could lead to unintended consequences.” There are unavoidable limitations when doing research on animals. The brains of humans and animals are not the same so there will come a point when a drug will need to be given to a human and we will only know the true effects of it after the fact. It is hard to say now but it is most likely that the injection, if one is ever created, will have to be given to a child upon birth, and when that day comes it will be dependent upon mothers willing to let their child be a tester for a new drug.
If a single-dose injection could be used on the day of birth of a child born with Down syndrome, it could potentially continue the normal development of the cerebellum to a normal size instead of the stunted size. But we are far away from that happening, and at this point, it is impossible to even talk about hypothetical situations of using a similar drug on humans as was used on the mice. According to ABC News, “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.”
Although we are far from figuring out the hard wirings of Down syndrome, this experiment is a step in the right direction.
Avery Twible can be reached at avery.twible@spartans.ut.edu
