New Drug Found to Improve Memory

WASHINGTON — For the first time, an experimental drug has been shown to dramatically improve human memory and will be tested early next year on patients suffering from Alzheimer’s disease, researchers from UC Irvine announced Sunday.

The drug arises from a new class of biochemicals called ampakines, invented by UC Irvine neuroscientist Gary Lynch and his colleagues. They are believed to work directly on the mind’s machinery of memory by enhancing communication among brain cells.

Preliminary research suggests to some scientists that these substances may help treat a variety of mental disorders, such as Alzheimer’s and schizophrenia, in which the high-speed electrical signals that link the brain’s complex neural circuits are failing. It could even help offset some of the mental effects of normal aging.

Reporting the results of the drug’s first trials on human beings, Lynch on Sunday said ampakine significantly enhanced performance on simple memory tests.

There were no serious side effects, and the improvement appeared to be greatest among elderly test subjects.

The results of the three limited human studies, which will be published next year in the Journal of Experimental Neurology, were made public here at the annual meeting of the Society for Neuroscience.

The UC Irvine researchers conducted the tests in collaboration with the Karolinska Hospital in Stockholm, Sweden, and Cortex Pharmaceuticals Inc., a biotechnology company in Irvine that licenses the drug from the University of California.

“We are extremely optimistic about this,” Lynch said. “People who had the ampakine did better.

“The results with the patients between 65 and 70 years old were particularly striking. At the highest doses we used, the older people scored within the range of the young people. That was rather exciting.”

Other experts on the human brain and its diseases greeted Sunday’s announcement cautiously.

Dr. Donald Price, a respected neurologist at Johns Hopkins University in Baltimore, called the work “very preliminary.”

Price questioned whether the drug could be a useful way to improve memory among healthy people or to alleviate the kinds of memory loss associated with normal aging. He noted that its effects are temporary and that there so far is no information to indicate it will help anyone with Alzheimer’s disease.

“It is intriguing. It is innovative. It is worth pursuing. But is it a breakthrough?” he said. “It is too early for me to be enthusiastic. I would like to see a lot more studies of what it does in cells, in animals and what it does to humans in bigger clinical trials.”

Human tests have proceeded slowly and the scientists have worked with only very small doses of the new chemical in order to minimize its effects until its impact on normal human thought processes is better understood.

“It is hard to emphasize enough how we are moving into uncharted territory here,” Lynch said. “There is no analogous drug” that acts so directly on the fundamental biochemistry of mental activity. “We are terrified of side effects.”

Cortex President Vincent F. Simmon said the company signed an agreement Friday with the National Institutes of Health for a clinical evaluation of the drug’s effects on 16 people with moderate Alzheimer’s disease--the first in what researchers hope will be a series of clinical trials.

So far, the drug has been tested on only 54 people, ranging in age from 21 to 73. Their memories were tested before and after taking the drug, using an array of word games, mazes, photograph-identification tests and other mental exercises.

On average, Lynch said, people using the drug scored twice as well as those who did not. The effect was rapid and short-lived, preliminary tests and brain scans showed.

Gary A. Rogers, vice president of medicinal chemistry at Cortex, said Sunday that the company has already developed new ampakine compounds “1,000 times more potent and with a better safety profile” than the version used in the preliminary human tests. The drug, which has the trade name Ampalex, can be taken as a pill.

If subsequent tests of the drug bear out its preliminary success, it will offer a way to deal with the memory loss that is a devastating symptom caused by Alzheimer’s.

The number of people diagnosed with Alzheimer’s is expected to triple to 15 million during the next 25 years because the elderly are the fastest-growing segment of the U.S. population. It is estimated to strike 7% of people older than 65 and 40% of those older than 80.

The exact nature of the memory problems caused by the disease is still unknown. Researchers are still trying to learn whether the disease interferes with the brain’s ability to retrieve memories or whether it disrupts the brain’s ability to encode and store memories.

Zaven Khachaturian, director of the Alzheimer’s Assn.’s Ronald and Nancy Reagan Research Institute in Chicago, said he was impressed with the drug’s apparent ability to improve the performance of the brain’s neurons, but he emphasized that memory difficulties were only one of the debilitating effects of Alzheimer’s disease.

“Any effort that is going to slow, prevent or reverse the loss of memory is going to be a major contribution to Alzheimer’s patients and their families,” he said. However, “we all know that many of these promising compounds do not finally make it through the regulatory system.

“So far we have been frustrated by the fact that we catch the disease only after large numbers of neurons have been destroyed.”