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Cancer drug being repurposed to treat Fragile X Syndrome

5.3.17 | WisBusiness.com | Alex Moe | Original Publication

Researchers at UW-Madison are trying to repurpose an antitumor drug to treat a common intellectual disability known as Fragile X Syndrome.

And Professor Xinyu Zhao, a professor of neuroscience at UW-Madison who’s heading up this research, says initial tests in rodents show promise for this experimental treatment option.

“This could be a new way to treat, at least, cognitive function in Fragile X patients — at least worth exploring,” Zhao said.

The Wisconsin Alumni Research Foundation is seeking commercial licensing partners for the patent, which covers the use of Nutlin-3, a candidate antitumor drug, to treat Fragile X Syndrome.

FXS is a genetic disorder characterized by irregularities in a protein called fragile X mental retardation protein, or FMRP. This protein is needed for brain development, and people with FXS don’t produce it at all.

The condition affects both males and females, though females often have less severe symptoms. Though exact rates of affliction are unclear, according to the Centers for Disease Control and Prevention, about 1 in 5,000 males is affected.

Some common signs of FXS in children are: developmental delays like not sitting up or walking at the same time as other kids; difficulties learning new skills; and social issues like failure to make eye contact, erratic movement and overactivity.

Autism Spectrum Disorders, or ASDs, are seen more frequently in people with FXS.

Though treatment with Nutlin-3 has been found to improve cognitive function in mice with FXS, this research is still in its preclinical stage, and a lot more work needs to be done to determine if it will have the same effect in humans, according to Zhao.

Ongoing research at UW-Madison’s Waisman Center is finding that, despite the significant biological differences between mice and people, certain behaviors can be observed that provide insight into how treatment would impact a patient.

To test spatial learning and cognitive recognition, researchers place two objects into an enclosure, and introduce mice into the space. They run around investigating the objects, forming memories about the environment based on spatial cues.

Researchers then take the mice out, shift the objects’ locations, and put them back in. The mice will remember the previous configuration and investigate the new locations; researchers then score the percentage of time spent in the new spots.

Normal mice mostly spend their time investigating the newly moved objects; mice with FXS don’t seem to remember there was a change.

“Spatial memory is really important; for example, you park your car in one corner of the lot, you have to remember that when you leave,” Zhao explained. “Temporary, but very important as it’s related to location.”

Nutlin-3 has been found to reduce some effects of FXS both in vitro and in mice models — that’s what makes it so attractive as a potential treatment option, Zhao said. She adds other cancer treatments could potentially be useful as well.

“Lots of cancer genes are actually also mutated, changed in autism and developmental disorders,” Zhao said. “They actually have lower rates of cancer, but the same genes that mutated in cancer, also mutated in developmental disorders. That’s why I think a lot of cancer treatments have great potential to be repurposed to treat neurological disorders.”