Total Recall: Drug shows long-lasting boosts of memory in rats

An experimental drug completely regenerates parts of the brain crucial to forming memories, according to researchers who performed tests on rats. Moreover, the drug’s effects linger after it clears from a rat’s system, so it may lead to a convenient treatment for people with disease-related memory loss, they say.

As people reach age 30, the neural mechanisms that form memories begin to deteriorate. Some diseases accelerate that decline. One strategy to restore this capacity is to increase production of a protein called brain-derived neurotrophic factor (BDNF), which stabilizes the memory-making operation.

Studies of cells in the laboratory have shown that drugs called ampakines elevate production of BDNF. One ampakine is currently being tested in people with Alzheimer’s disease.

In the new study, researchers gave another ampakine, called CX929, to 8-to-10-month-old rats whose memory mechanisms had totally deteriorated with age, reports Julie Lauterborn of the University of California, Irvine.

Some of the rats received two daily doses of the ampakine for 4 days, while others received no treatments. About 18 hours after the rats’ final treatments, an analysis of tissue from the hippocampus, the brain’s memory hub, showed that the treated rats had twice as much BDNF in their brains as the untreated rats did, Lauterborn and her colleagues report in the August Journal of Neurophysiology.

The study is the first to show that ampakines can increase BDNF concentrations, the researchers say.

Moreover, tests showed that the treated rats’ memory functions had returned to “100 percent of what the normal young animal would be,” Lauterborn says.

The drug stays in the rats’ systems for only about an hour, so seeing its effect 18 hours later was “really surprising,” Lauterborn notes. If CX929 is developed into a drug for people, “you may only need to take one pill a day, and you can have carryover effects for the next day for memory mechanisms,” she suggests. Most memory-recovery drugs now in use must be taken several times a day.

The experimental drug shows great promise for treating diseases that impair memory, including Parkinson’s and Huntington’s, says coauthor Gary Rogers, a researcher at Cortex Pharmaceuticals in Irvine, Calif., which is developing the drug.

“Now, for Alzheimer’s, [drugs] barely treat symptoms. CX929 would perhaps actually modify the outcome of the disease,” he says.

The company, which contributed the drug for the rat study but did not fund it, is performing a trial of a different, less powerful ampakine in people. Such clinical testing should begin next year on the ampakine used in the new study, Rogers says.

The data from the rat study look as good as one could hope for, says neural scientist David M. Katz of Case Western Reserve University in Cleveland.

“The fact that they can reverse this age-related decline in hippocampal function, that in and of itself is important,” Katz says. “That they can do it using a drug that has promise for clinical efficacy in humans is very exciting.”