A pill to make you smarter

The researchers’ work, done on rodents, builds on findings that all mammals, including humans, make brain cells throughout their lives. Most of these die, but this drug helps more of the baby cells survive and grow to become functioning brain cells.

"We make new neurons every day in our brain," Andrew Pieper of the University of Texas Southwestern Medical Center in Dallas who worked on the study, said in a telephone interview. "What our compound does in allow more of them to survive."

The compound is called P7C3 for now, and the researchers have already started tweaking it to make it more effective. They said it seems safe and appears to work even when taken as a pill.

The compound is similar to Medivation Inc and Pfizer Inc’s experimental Alzheimer’s drug, Dimebon, and may provide ways to improve its effects, Pieper and colleagues reported in the journal Cell.

It is also similar to some compounds owned by Serono, the researchers said.
Dimebon, originally a Russian-made antihistamine also known as latrepirdine, failed in a clinical trial for Alzheimer’s disease in March.

“For the sake of patients suffering from Alzheimer’s disease, it is hoped that the apparently marginal clinical utility of Dimebon might be enhanced by improvements in both its potency and ceiling of proneurogenic, neuroprotective efficacy,” the researchers wrote.

“If so, our work offers concrete assays for the development of improved versions of these neuroprotective drugs.”

Alzheimer’s gradually destroys the brain and affects 26 million people globally. Drugs, such as Pfizer’s Aricept, improve symptoms only minimally. 

The researchers went through 1,000 representative compounds from 300,000 chemicals, pooled them and administered them to mice. They then dissected the brains to see whether any of the mice had made new cells in the hippocampus, a region of the brain associated with learning and memory.

Old rats, new tricks

They eventually narrowed the field to P7C3. When they gave it to old rats for two months, the elderly rodents did far better than other old rats in learning their way around a water maze. When dissected, the treated rats turned out to have three times the usual number of newborn neurons in a brain region called the dentate gyrus.
They made a derivative of P7C3 called A20 that worked even better.

When the researchers tested Dimebon and the Serono compounds, they found these drugs also stimulated the growth of new brain cells. Being able to target their effects could lead to better drugs to treat Alzheimer's and perhaps other diseases that destroy brain cells like strokes and amyotrophic lateral sclerosis, also know as ALS or Lou Gehrig’s disease.

“This striking demonstration of a treatment that stems age-related cognitive decline in living animals points the way to potential development of the first cures that will address the core illness process in Alzheimer’s disease,” said Thomas Insel, director of the National Institute on Mental Health, which helped pay for the study.