Wednesday, October 5, 2022

Cancer Drugs Can Prevent Brain Disorders

Researchers from the University of Michigan Life Sciences Institute have found out that a specific type of cancer drug could help prevent issues with brain cell development. These brain cell development issues are commonly associated with disorders like Down Syndrome and Fragile X syndrome.

downs

Researchers used fruit fly models as part of the concept study, and the models showed the brain dysfunctions found in people. This research study was published in the journal of eLife. The study showed that when the fruit fly larvae that had the equivalent of Fragile X were given leukemia drugs such as nilotinib or bafetinib, it helped prevent the overgrowth of neuron endings that are found with the disorder. The cancer drugs are what is known as tyrosine-kinase inhibitors, and neither of them adversely affected the development of the neurological growth in the healthy flies.

The study shows that there possibly a therapeutic approach to help treat these types of brain disorders that are associated with a dysregulated Dscam protein expression. This dysregulation is seen in both Down syndrome and the Fragile X syndrome. The senior study author is Bing Ye, while graduate student Gabriella Sterne and postdoctoral fellow Jung Hwan Kim are co-first authors of the study. In terms of intellectual disabilities, Fragile X and Downs syndrome are the two most common genetic causes. When someone has Down syndrome they have an extra copy of Chromosome 21, and Fragile X is when there is just a single gene mutation. The Ye lab and other institutional researchers have found out that there is a possible link between the two conditions through various studies.

When a fetus is in early development, the neurons will end up producing a high amount of the protein which is encoded by the DSCAM gene, this is during the process when the neurons are undergoing branching to connect them to the other neurons. If you have never heard of DSCAM before, this is short for Down Syndrome Cell-Adhesion Molecule. When the Dscam levels do not go back down for whatever reason, this is when Downs syndrome can occur. When the Dscam levels stay high in the flies, it can end up making a faulty connection with the neurons next to it. Humans have a far more complex brain and nervous system, which then makes it more difficult to figure out how the Dscam dysregulation occurs.

There were a number of experiments done in this study, which the researchers were able to show how the Dscam protein activates and Abelson tyrosine kinase protein. The scientists were then able to genetically modify the flies that produced the higher levels of Dscam, and gave them the cancer drug. The cancer drug blocks the actions that are produced by the Abelson tyrosine kinase protein. One of the experiments showed that when the flies that had overexpressed Dscam were looked at, the neuron endings were about 50 percent longer than normal. In the flies that were treated with the cancer drugs, the neurons only increased about 15 percent. When the researchers looked at genetic models of Fragile X, they noticed that the presynaptic terminals on the flies were about a third longer than normal, but the flies with the drugs only had about a 3 percent more than normal growth in the terminals.

More studies will be needed however because even though flies and people are similar, it’s still unclear whether this type of treatment would be safe for humans. There is also still a lot of work to be done in figuring out how the dysregulation occurs in humans, so it’s not like the cancer drugs could be used anytime soon on people, although the hope is that more funding could be used towards getting clinical trials sometime in the future. Using mouse models would be the next step, then getting oncologists and pharmaceutical companies to collaborate on the project is also needed, and then possibly human trials could occur if the mouse models also show the same results. For now, it looks like researchers are getting one step closer to finding out how to prevent these neurological disorders.

Jeanne Rose
Jeanne Rose lives in Cincinnati, Ohio, and has been a freelance writer since 2010. She took Allied Health in vocational school where she earned her CNA/PCA, and worked in a hospital for 3 years. Jeanne enjoys writing about science, health, politics, business, and other topics as well.
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