New clues to memory loss could advance Alzheimer's research

Researchers from Edinburgh University have published a study demonstrating the abiliy of a new experimental compound to actually restore the memories of mature mice, which could lead eventually to improved quality of life for normal elderly people as well as the development of treatments for memory related diseases such as Alzheimer's.

The typical symptoms of age related memory loss, such as forgetting people’s names or the whereabouts of car keys are generally accepted as being due to high levels of 'stress' steroid hormones known as glucocorticoids. An enzyme called 11beta-HSD1 is involved in making these hormones and has been shown to be more active in the brain during ageing.

In a study published today in the Journal of Neuroscience , the team relates how the administration of a new synthetic compound selectively blocks 11beta-HSD1 on mice which are then subjected to the Y maze memory task.

“Normal old mice often have marked deficits in learning and memory just like some elderly people,” explained Professor Jonathan Seckl from the University of Edinburgh, who discovered the role of 11beta-HSD1 in the brain.

“We found that life-long partial deficiency of 11beta-HSD1 prevented memory decline with ageing. But we were very surprised to find that the blocking compound works quickly over a few days to improve memory in old mice suggesting it might be a good treatment for the already elderly.”

In fact the study reports that positive effects were discernable after only 10 days.

Leading the drug development are Professor Brian Walker and Dr Scott Webster from the University of Edinburgh.

“These results provide proof-of-concept that this class of drugs could be useful to treat age-related decline in memory,” Professor Walker said.

“We previously showed that carbenoxolone, an old drug that blocks multiple enzymes including 11beta-HSD1, improves memory in healthy elderly men and in patients with type 2 diabetes after just a month of treatment, so we are optimistic that our new compounds will be effective in humans. The next step is to conduct further studies with our preclinical candidate to prove that the compound is safe to take into clinical trials, hopefully within a year.”

The Edinburgh team has also been responsible for establishing links between the 11 beta-HSD1 enzyme and metabolic diseases such as diabetes and obesity, with similar drugs designed to block its activity outside of the brain currently under investigation.

The study was supported by the Wellcome Trust and the Medical Research Council (MRC). The drug development programme in Edinburgh is supported by a Seeding Drug Discovery award from the Wellcome Trust.

Dr Rick Davis of the Wellcome Trust commented: “Developing drugs that can selectively inhibit this enzyme has been a challenge to the pharmaceutical industry for nearly ten years. Advancing this compound towards clinical trials takes us a step closer to finding a drug that could have far reaching implications as the population ages.”