Learning & Memory

Existing cancer drug boosts brain genes to improve memory and learning

Existing cancer drug boosts brain genes to improve memory and learning
New research has shown that an existing cancer drug can help improve memory by boosting the expression of certain genes
New research has shown that an existing cancer drug can help improve memory by boosting the expression of certain genes
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New research has shown that an existing cancer drug can help improve memory by boosting the expression of certain genes
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New research has shown that an existing cancer drug can help improve memory by boosting the expression of certain genes

Researchers at EPFL have found that an existing drug used to treat cancer, among other things, also seems to improve memory. Intriguingly, tests in mice show that the drug works by switching on genes associated with brain plasticity.

The drug in question belongs to a class known as HDAC inhibitors (HDACis), which are used for a variety of purposes. This particular one is called CI-994, and it’s administered as a chemotherapy adjuvant, improving the efficacy of the treatment against cancer. Other studies have suggested that the drug also seems to act as a cognitive enhancer in animals, but how it worked in that regard remained unknown.

For the new study, the EPFL scientists investigated just that. In a common test for associative memory, the team used a contextual fear conditioning method to teach mice to fear a certain trigger. When the mice were given CI-994, they doubled their memory capacity for the task as compared to mice that learned without the drug.

But how did it work? The team examined a hypothesis that the HDACis were operating through a process called epigenetic priming – essentially, changing the expression of certain genes. In this case, the affected genes are related to learning and memory.

And sure enough, RNA sequencing techniques showed that the drug was acting on specific genes that control synaptic plasticity, the process that allows neurons to form stronger connections to facilitate memory and learning. On these key genes, the drug was making DNA packages called chromatin more accessible, easing their expression.

“The drug supports very specific genes, the ones that are already engaged in learning, and it doesn’t affect much other genes, for example genes that could have unwanted side-effects,” said Johannes Gräff, lead author of the study.

Understanding how these HDACis function is important for potentially putting them to work on improving memory and learning in humans. Thankfully they’ve already been approved for use in humans and shown to be safe, which speeds up the process of adapting them for new purposes. Two other clinical trials are already underway, exploring the use of the drug in improving memory in Alzheimer’s patients, and to help unlearn a fear of spiders.

The research was published in the journal PNAS.

Source: EPFL

4 comments
4 comments
guzmanchinky
The levels of advancement keep getting faster. I'm 51 and my mother died of dementia at 80, so I'll be keeping an eye on this...
Ralf Biernacki
Until human trials, we will never know what the side effects really are. Perhaps the increased plasticity "enhances" forgetting as well as forming new memories. Perhaps it does something else. The mice won't tell you. But if plasticity genes are naturally suppressed in adults, probably there is a good reason---good enough to offset its evolutionary advantages. Even so, this discovery is important enough to warrant further research---on subjects who can _describe_ their cognitive experience.
Username
@Ralf. the drug is already used on humans to treat cancer.
Karmudjun
Yes, this adjuvant drug shows promise. I would like to see it in human trials for optimal brain plasticity response and for tolerance information. Using something to enhance a chemotherapy regimen doesn't give you enough usage information to recommend joining a study, much less prescribing CI-994 in the real world. Two studies - one with an alzheimer's cohort and another with an arachnophobia cohort - will these provide the detail for dosing and for the highest tolerated dosages? Are they planning on Functional MRI studies to further tease out all of the brain areas affected by this drug sans chemo? Great write up Michael, thanks!