Down syndrome and Fragile X syndrome are the most prevalent causes of genetic intellectual disability. Searching for and finding ways to treat the genetic anomalies that cause Down syndrome and Fragile X may very well be the best way to eradicate these diseases. Albeit it early, researchers at the University of Michigan Life Sciences Institute have received some very promising results in this search using
FDA-approved cancer drugs.
The researchers' proof-of-concept study using fruit fly models of brain dysfunction was published today in the journal eLife. They show that giving the leukemia drugs nilotinib or bafetinib to fly larvae with the equivalent of Fragile X prevented the wild overgrowth of neuron endings associated with the disorder. Meanwhile, the drugs--both tyrosine-kinase inhibitors--did not adversely affect the development or neuronal growth in healthy flies.
"This study proposes a potential therapeutic approach for treating brain disorders associated with dysregulated expression of the Dscam protein, which is seen in both Down syndrome and Fragile X syndrome," said senior study author Bing Ye, whose lab is in the LSI. Graduate student Gabriella Sterne and postdoctoral fellow Jung Hwan Kim are co-first authors of the paper.
The paper can be found
here. This is just one of the first steps towards very promising treatments for these
genetic disorders.
"Although there's an amazing amount of similarity between flies and humans, more study is needed before we'll know if this could be a safe and effective treatment for human patients," said Ye, who is also an assistant professor in the Department of Cell and Developmental Biology at the U-M Medical School.
The next step would be to test the approach in mouse models of these brain disorders. Collaborations with oncologists and pharmaceutical companies will also be essential to ensure Abl inhibitors are safe to use in this context, Ye said.