Patients of Alzheimer's take heart, `smart gene' is on the way
REUTERS

Washington, June 20: Genetic engineering has produced a strain of super-smart mice and may point to a way to help patients with Alzheimer's, mental retardation and perhaps even the annoying "senior moments" that come with ageing, researchers said on Monday.

The protein, GAP-43, has long been associated with learning. Mice that got extra boosts of the GAP-43 gene did much better in mouse mazes used to test rodent intelligence, Aryeh Routtenberg at Northwestern University and colleagues found.

What they do not have, Routtenberg stresses, is a "smart pill." "Is this a smart drug? Of course it's a gene, so you can't take it," he said in a telephone interview.

But he thinks it may be possible to manipulate brain cells so that they produce more GAP-43 when necessary.

"The important point here is that we have the first good evidence that this protein actually regulates learning," Routtenberg, who reported his findings in the proceedings of the National Academy of Sciences, said.

He said GAP-43 is found early in the development of all animals, when neurons are deciding where and how to grow. It is found in high concentrations in, for example, one-day old mice and he believes the combination of stimulation -- such as exploring a new environment -- and having high levels of the protein helps an animal learn.

"It maintains the juvenile character ... the childlike appreciation of things," he said.

"It's the same molecule in rodents, monkeys and in man," he added. "It looks like it is regulated in more or less the same way."

Routtenberg's team used mice genetically engineered to produce extra levels of GAP-43. He said a Swiss team created the mice, using both the GAP-43 gene and a related bit of DNA called a promoter.

The mice were much quicker to learn than "wild-type" mice. But the gene had to work just right. Tweaking it to produce a very slight mutation ruined the effect.

"The protein by itself is not active unless it has phosphate group on it," Routtenberg said. That process of adding a phosphate molecule, called phosphorylation, is key to activating many genes.

If researchers could find a way to phosphorylate GAP-43 in humans, it might be a way to help learning without resorting to genetic engineering, he said.

Years of research were needed, but Routtenberg said something as simple as salad oil, with its content of certain fatty acids such as linoleic and oleic acid, might do the trick.

"We injected olive oil into the brains of rats and found we could facilitate GAP-43 phosphorylation," he said. "In dietary studies, corn oil was especially useful in facilitating memory."

Strains of mice exist that are naturally more intelligent and Routtenberg found that those mice had high levels of GAP-43. That convinced him that he was on the right track.

He said he and other researchers also found natural cycles in GAP-43, for example in ovulating rats.

"We probably endogenously have those moments. You surely have had times when listening to something when it is all clicking and the next day you just remember it," he said.

Routtenberg said he would oppose moves to create a designer drug for people who want to be smarter, or who want their children to have an advantage in school. "You get into ethical questions," he said.

"But I think that we are moving ever closer to finding an agent that will facilitate when we are learning."

Legitimate uses, in his opinion, would be in treating people with Alzheimer's, some with mental retardation and perhaps people suffering from age-related memory loss.

He said there was evidence that GAP-43 was produced in lower amounts as people aged.

Copyright © 2000 Indian Express Newspapers (Bombay) Ltd.