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Alzheimer's memory loss due to gene blockade reversed in mice

5 March 2012
Appeared in BioNews 647

An enzyme associated with memory loss can be blocked to reverse symptoms of Alzheimer's disease in mice, a study has shown.

The enzyme, called histone deacetylase 2 (HDAC2), is overproduced in people with the disease. The researchers, based at Massachusetts Institute of Technology (MIT), suggest that a drug to inhibit HDAC2 could be developed to help Alzheimer's patients.

HDAC2 affects genes responsible for learning and forming new memories. HDAC2 doesn't directly inhibit the genes, but instead interferes with gene expression epigenetically. It does this by causing the DNA strand to become more tightly wound, effectively hiding sections of DNA from the proteins that read and activate the genes.

'If your memory is everything that you know written in a book, then in order to have access, you have to open the book and to turn the pages', Dr Johannes Graff, the study's lead author, told US News. In Alzheimer's, 'this mechanism actually closes your memory book and makes the pages - the genes - inaccessible'.

Previous research suggests that a major cause of Alzheimer's disease is the formation of protein fragments called beta-amyloids, into solid plaques. These plaques clog up the space between brain cells and stop them functioning correctly.

This is not contradicted by the new findings. Indeed, the team at MIT suggests that beta-amyloids may actually trigger overproduction of HDAC2. However, reducing plaque formation would not reverse symptoms of Alzheimer's after HDAC2 had begun its work.

Although the current research identifies a new target for drug therapy in Alzheimer's disease, it may take a long time before an HDAC2 inhibitor becomes available. 'Clinical trials for a new drug may take as long as five years to begin', said Dr Li-Huei Tsai, the research group's team leader. 'If everything goes well, to become an approved drug would probably take at least ten years'.

Dr Brad Dickerson, associate professor of neurology at Harvard Medical School, who was not involved in the study told US News that 'the leap from animal studies to human clinical trials is a big one and always takes many years'. However, he mentioned that HDAC2 inhibitors are currently under investigation as cancer drugs. Those trials, he said, 'will provide an indication of their side effects and other important information'.

The Alzheimer's Society states that there are currently 750,000 people with Alzheimer's disease in the UK.

Alzheimer's-Like Memory Loss Reversed in Mice
US News |  29 February 2012
An epigenetic blockade of cognitive functions in the neurodegenerating brain
Nature |  29 February 2012
Inhibiting Alzheimer Enzyme Could Reverse Memory Loss
EmaxHealth |  03/12
Reversing Alzheimer's gene 'blockade' can restore memory, other cognitive functions
EurekAlert! |  29 February 2012
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