The researchers at University of Michigan have done a proof-of-concept study by using fruit fly models of brain dysfuction which was published in the journal called ‘elife' on Wednesday.
They have shown the association with the disorder can prevent the wild overgrowth of neuron endings by giving leukemia drugs nilotinib or bafetinib to fly larvae which is equal to Fragile X. Meanwhile, the drugs -- both tyrosine-kinase inhibitors - have not adversely affected the neuronal growth in healthy flies.
"This study proposed a potential therapeutic method for treating brain disorders which was seen in both Down syndrome and Fragile X syndrome are associated with dysregulated expression of the Dscam protein", said Mr Bing Ye, Graduate student, Ms Gabriella Sterne, and Mr Jung Hwan Kim, post-doctoral fellow, are co-first authors of the papers.
Down syndrome and Fragile X are the most prevalent genetic causes of intellectual disabilities. Down syndrome is caused by an extra copy of chromosome 21, and Fragile X is caused by a mutation in a single gene. Recent studies by the Ye lab and by the researchers from the other institutions, have pointed to a possible link between these two circumstances.
During early the development, neurons has produced high levels of the proteins which is encoded by a gene called Down Syndrome Cell-Adhesion Molecule (DSCAM). DSCAM has undergone an intense period of extension and has branched to connect with the other neurons. But the problem could arise when DSCAM levels don't go down.
In flies, when DSCAM levels goes high, it branches off of the ends of their neurons which grows too long and make faulty connections with the neighboring neurons. In humans, whose nervous systems and brains are far more complicated, the downstream impacts of DSCAM dysregulation have not been completely identified.
"Although there has been an amazing amount of similarity between flies and humans, more study was needed before we would know if this could be a safe and effective treatment for the people, and this study was also an example of the model organism utility" said Mr Ye, Assistant Professor, Cell and Developmental Biology Department, U-M Medical School. He continued, "Fruit flies grew and developed rapidly -- and although the behaviors of flies and humans are very different, neurons of humans grew as much in the same way, and the genes which were controlling this process were usually similar."
This work was supported by grants from the National Institutes of Health, the Protein Folding Disease Initiative, University of Michigan and the Pew Scholars Program in the Biological Sciences. University of Michigan has a patent application based on this discovery and is looking for a commercial partner to develop it into treatments.
