Kiwis close in on drug for Alzheimer's

Professor Matthew During at work in an Auckland Medical School laboratory. Picture / Martin Sykes

Auckland scientists have successfully blocked age-associated memory loss in rats and hope it will be possible to stop memory decline in humans, thereby preventing conditions such as Alzheimer's.

The solution, according to Professor Matt During's study, lies in the protein CREB, widely recognised as significant in the formation and use of long-term memory in mammals.

"There's plenty of it when we're born, and as we get older we lose this protein, so the levels drop. If you maintain the levels of the protein, you can actually prevent the degeneration," said Dr During.

He and his Auckland University colleagues observed improved memory and learning ability in elderly rats when the protein's "expression" was doubled in the hippocampus, the part of the brain that plays a part in memory and navigation.

But the higher protein levels had no effect on the same animals when they were younger. The findings have been published in the US journal Proceedings of the National Academy of Sciences.

"The critical thing with this paper is that until now, people have been interested in this specific protein with memory but no one's ever demonstrated that it's a cause, or that maintaining it could actually prevent the decline of memory with ageing."

To obtain their findings, the researchers injected viral particles laced with genetically engineered CREB into the dorsal hippocampus of 8-week-old rats to achieve long-term "expression" of the protein in the hippocampi. After the gene therapy, the animals were tested at three and 15 months in a variety of behavioural tasks.

At three months, the researchers found the animals performed similar to age-matched rats which did not undergo the treatment. But at 15 months, the injected rats performed considerably better in passive-avoidance tests, and in the Barnes circular table test, where the animals must remember where to find an escape hole.

In the latter test, the CREB-boosted animals found sanctuary faster than the control litter mates.

Dr During said the discovery gave new ways of fighting age-related memory loss in humans; either through a direct injection to the brain, or less invasively through ingested drugs that increase CREB levels.

He and his team hope to explore the less invasive option further, and to see if increasing CREB levels can help reverse or alleviate the late stages of profound memory deficit. Preliminary data from another of Dr During's studies suggests that it could be protective against Alzheimer's as well.

Dr During was involved in a breakthrough operation at Auckland Hospital in 1996 in which surgeons implanted synthetic genes in the brains of two American infants suffering Canavan disease, a rare and fatal brain disorder.

FAMOUS SUFFERERS

* Children's author Enid Blyton.
* Former US President and actor Ronald Reagan.
* Writer Iris Murdoch.
* Actor James Doohan (Scotty in Star Trek).
* Abstract expressionist painter Willem de Kooning.