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Cancer Drug May Fight Memory Loss of Early Alzheimer's

A drug now used to treat cancer may also be able to restore day-to-day memory in Alzheimer’s patients, according to research findings published in the Journal of Alzheimer's Disease.

Day-to-day memories are often the first elements of the mind to slip away in Alzheimer’s, making the discovery of HDAC inhibitors’ effectiveness by Columbia University scientists all the more significant. HDAC inhibitors – or histone deacetylase inhibitors – are a class of compounds that interfere with the function of enzymes by influencing a person’s DNA.

 

"People often joke that they must have Alzheimer's because they can't remember where they put their keys, but for a person with the disease, this type of short-term memory loss is extremely debilitating," said the study's lead author, Ottavio Arancio, PhD, associate professor at the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center in New York.

 

Arancio said the Alzheimer’s benefit was uncovered by using the cancer drug to targets a previously unknown defect in the brains of mice with Alzheimer's.

 

He said it appears the memory improves with HDAC inhibitors because they affect the way the brain records new memories. To create new memories, the neurons in the brain must manufacture new proteins. The first step is to open up and read the DNA, which contains instructions for making the proteins.

 

Study co-author Yitsak Francis, PhD, said the neuron attaches a chemical reactive group to the spool around which DNA is tightly wound in order to read the DNA. "These groups, called acetyls, unwind the DNA to make it more accessible," said Francis, a postdoctoral research scientist at Columbia. "It's like unwinding knitting wool from its spool."

 

The scientists found that this unwrapping step is impaired in mice with a form of Alzheimer's. The study mice with Alzheimer's attached about half as many acetyls to DNA as normal mice and had poorer memory.

 

The Columbia team then discovered that they could improve memory in the Alzheimer's-afflicted mice by applying the HDAC inhibitors, which actually increase the DNA's spool acetylation and gene transcription. In the end, the drug improved memory performance to the level found in normal mice.

 

"Because this type of drug has already been approved for some cancer patients," said co-author Mauro Fà, Ph.D., associate research scientist at the Taub Institute, "we hope that clinical trials for Alzheimer's disease can start in about three to four years."

 

"For making memories, you need transcription and protein synthesis at the cellular level. If you don't have that, you don't have memory," Francis emphasized.

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