A class of drugs normally used to treat cancer has shown early success in fruit-fly models at minimizing the expression of Down syndrome and Fragile X syndrome, a new study reports.
Though still in their initial stages, the experiments suggest a novel approach to studying intellectual disorders. According to the Centers for Disease Control and Prevention, Down syndrome occurs in roughly one in 700 children, with both life span and prevalence increasing in recent years. Though scientists are learning more about how to manage life with the disorder, which arises from an extra copy of chromosome 21, they still have yet to find a way to stop it at the source.
The research hinges on the expression of a protein known as DSCAM, the Down syndrome cell-adhesion molecule. During development, brain cells rely on an overproduction of DSCAM to join with other neurons. But at some point DSCAM has to stop adding length to the neurons’ arms, otherwise they’ll make faulty connections with neighboring cells. It’s thought disorders of the brain, including Down syndrome and Fragile X, that arise when DSCAM production fails to quit.
“This study proposes a potential therapeutic approach for treating brain disorders associated with dysregulated expression of the DSCAM protein,” said senior study author Bing Ye, of the University of Michigan Life Sciences Institute, in a statement.
Ye and his colleagues rigged an experiment in genetically modified fruit flies in which the DSCAM overproduction also led to an overproduction of a protein called Abelson tyrosine kinase (Abl). By checking the relative levels of Abl after giving the flies drugs for leukemia, the team could also measure how long or short the ends of the neurons grew. If they were shorter than average, the drugs were working.
In one experiment, the flies made to overexpress DSCAM had neuron ends that were 50 percent longer than average. But in delivering the cancer drugs, the ends only developed to 15 percent longer than flies with normal amounts of DSCAM. In another experiment, this time focusing on a model for Fragile X, the length reduced from 33 percent longer to just three percent.
To Ye and the other investigators, this suggested dramatic implications for controlling the development of young brains with drugs normally reserved for adult forms of cancer. It also validated the patterns between human gene expression and that of others species. At the risk of overextending the claims, however, as a next-step point of inquiry they must first elucidate the differences between human brains and mouse brains.
“Although there’s an amazing amount of similarity between flies and humans,” Ye said, “more study is needed before we’ll know if this could be a safe and effective treatment for human patients.”