Anti-Cancer Drugs, Histone deacetylase inhibitors (HDACis), Help Improve Memory

From Dale Bredesen:

A chemotherapy drug was found to enhance memory by improving communication between neurons as a result of supporting brain cells’ ability to read the genes that are important for synaptic plasticity.

Clinical trials are currently underway to determine the improvement of memory in Alzheimer’s patients. It is good to see research expanding beyond the Amyloid Hypothesis, but treating the root cause contributors of decline will likely prove to be necessary for best outcomes.

Details from write-up:

EPFL scientists have discovered how an anti-cancer drug could be repurposed to improve memory. It does so by supporting the cell’s ability to read the very genes that are important for learning. The epigenetic mechanism of the drug is shown in mice.

Two clinical trials in Europe are currently underway, one with the goal to enhance the unlearning of fear of spiders, the other to improve memory in Alzheimer’s patients.

Full Research Paper:

The HDAC inhibitor CI-994 acts as a molecular memory aid by facilitating synaptic and intracellular communication after learning

Over recent years, multiple studies have indicated the potential of HDAC inhibitors (HDACis) as cognitive enhancers, but their mode of action is not fully understood. Here, we tested whether HDACi treatment improves memory formation via “cognitive epigenetic priming,” stipulating that HDACis—without inherent target specificity—specifically enhance naturally occurring plasticity processes. We found that combining HDACis with fear learning, but not either treatment alone, enhances synaptic plasticity as well as memory-promoting transcriptional signaling in the hippocampus, a brain area recruited by fear learning, but not in unrelated areas. These results lend experimental support to the theory of cognitive epigenetic priming.

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Another potential drug for memory improvement / Alz. / Dementia:

“There is a lot of inhibition in a healthy brain,” Gallagher says. “There are neurons that suppress others so there isn’t too much noise in the brain. Greater activation can make the brain work less efficiently.”

Moreover, Gallagher hypothesized, this increased activity was pushing tau and amyloid to move throughout the brain, further accelerating the spread of plaques and tangles. Gallagher began looking for a drug that could quiet this activity. After extensive research, she identified a compound, levetiracetam, that calms these hyperactive brain episodes. Levetiracetam has been approved by the Food and Drug Administration to treat seizures in epilepsy patients, when used in conjunction with other medications.

For more than a dozen years, Gallagher has been leading the laborious process of testing levetiracetam for this new use. First, she spearheaded a study that showed that levetiracetam calmed hyperactivity in the hippocampi of elderly rats with memory impairment. Then in 2008 she received a $1.3 million grant from the National Institutes of Health to test the drug on human subjects. That study, published in Neuron in 2012, showed that levetiracetam quieted overactive neurons of people with mild memory loss, helped improve their performance on cognitive tasks, and caused no major side effects. The study also showed that levetiracetam had no effect on people who do not have Alzheimer’s. In other words, it’s not a magic pill that would provide memory superpowers to those who do not have the disease.

Another memory related development:


The book also touches on broader lifestyle advice. Recently, research from the Lancet’s commission on dementia suggested up to 40% of Alzheimer’s cases could be prevented or delayed – much like heart disease and many cancers – by limiting 12 risk factors, from smoking to obesity and heavy drinking.

Restak advises his patients to quit alcohol by 70 at the latest. Over 65, he writes, you typically have fewer brain neurons than when you were younger, so why risk them? “Alcohol is a very, very weak neurotoxin – it’s not good for nerve cells.”

Related… a Cognition study: