Statins for Algernon: Cholesterol-lowering drug fights learning disability

In Daniel Keyes’ 1966 novel Flowers for Algernon (Harcourt), an experimental treatment gives a mouse and a learning-disabled man increased intellectual abilities. Real-life researchers, too, have strived to develop effective treatments for learning-disabled people. Now, a study in mice suggests that a drug for high cholesterol may reverse learning deficits caused by a common genetic disease.

The disease, known as neurofibromatosis type 1 (NF1), affects an estimated 1 in 3,000 people worldwide. Along with various physical symptoms, people with this disorder frequently have learning, memory, and attention problems. “Currently, there are no good treatment options for these people,” says Alcino Silva of the University of California, Los Angeles.

Research has shown that people with NF1 produce too much of a protein called Ras, which regulates how nerve cells communicate. Because the functioning of Ras requires fatty molecules called lipids, Silva and his colleagues wondered whether reducing blood-lipid concentrations might alleviate symptoms of NF1.

The team worked with adult mice, some normal and others genetically altered to develop NF1. The rodents all ate peanut butter pellets, some of which contained a dose of lovastatin, a commonly prescribed statin drug that lowers the blood concentration of the lipid known as cholesterol.

After several days of treatment, the researchers examined the animals’ brains. The NF1 mice that had received lovastatin showed brain concentrations of Ras comparable to those of the normal animals, with or without lovastatin treatment. NF1 mice that hadn’t received the drug had higher amounts of Ras in their brains than the other mice did.

Curious about whether lowering Ras in the NF1 mice could improve cognitive function, Silva’s team gave new groups of mice the same dosing regimens. After 3 months, the scientists subjected the animals to a bevy of cognitive tests.

While NF1 mice that received lovastatin functioned much as normal mice on both treatment regimens did, NF1 mice that didn’t receive the drug functioned far worse.

Silva and his colleagues report these findings in the Nov. 8 Current Biology.

The results imply “that we can rescue cognitive deficits … even in mature patients,” says study coauthor Robert Brown. “The thing we’re really excited about is that we think this will be applicable in people.”

However, David H. Gutmann of the Washington University School of Medicine in St. Louis urges caution before assuming that lovastatin would benefit people, especially children. Previous research found that Ras plays an important role in wiring the brain during development.

Lowering the Ras activity “could have a great impact on the developing brain over years or decades of treatment. We need to learn more about the effects of long-term treatment in children,” says Gutmann.