Scientists find clues in search for dementia drugs
LONDON (Reuters) - Scientists have identified changes in mouse brains that impair learning, and say the findings mean drugs being developed for some cancers may also help fight age-related diseases like dementia and Alzheimer's.
German researchers studying mice at difference ages found that older mice had changes in proteins regulating the genes in their brains -- specifically in a process called histone H4K12 acetylation -- which slowed their ability to learn.
The discovery suggests that, over time, changes in the way our genes are expressed can lead to impaired memory and learning -- and that sudden deregulation of H4K12 acetylation could be an early warning sign of a brain starting to decline.
Medicines that help regulate such changes, known as histone deacetylase (HDAC) inhibitors, are already being developed by drugmakers such as Merck & Co for the treatment of some types of cancer.
Andre Fischer of the European Neuroscience Institute in Goettingen, Germany, who worked on the mouse study, said he now thinks more targeted versions of such medicines can be developed to treat patients with dementia or Alzheimer's.
"We have finished the first phase -- the pre-clinical phase -- and now it's time for the pharmaceutical industry to really try and drive it into application," he told Reuters in a telephone interview.
Dementia affects some 35 million people around the world and the number is set to balloon as populations age. Experts commenting on this study said it could have big implications.
Despite decades of research, doctors still have few effective weapons against dementia and Alzheimer's, which is the most common form of the brain-wasting disease.
Alzheimer's Disease International predicts the number of dementia sufferers globally will almost double every 20 years -- to 66 million in 2030 and more than 115 million in 2050.
DRUG RESTORED ABILITY TO LEARN IN MICE
In their study, Fischer and his colleagues gave various learning tasks to groups of mice aged 3 months, 8 months and 16 months to see when age starts to hamper mental ability.
After identifying the 16-month-old mice as the slowest learners, the researchers studied their brains and found their H4K12 acetylation function had failed.
As a result the 16-month-old mice were unable to properly regulate levels of genes associated with learning and memory, they found, and were unable to use the same key brain functions as the younger mice did to learn things.
When scientists gave the mice a drug which restored H4K12 acetylation and enabled the learning genes to be switched on again, the 16-month-old mice were able to learn and store memories once more.
Commenting on the study, which was published in the journal Science, David Sweatt of the neurobiology department at the University of Alabama, Birmingham, in the U.S., said scientists may now be "one step closer to understanding age-related memory loss and to developing a drug that might help boost memory".
"It's a real proof of concept," he said. "Studies in our lab and elsewhere strongly suggested that these drugs could potentially reverse ageing-associated memory dysfunction."
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