The new findings are published in the November issue of Current Biology.

"Learning disabilities and mental retardation each affect five percent of the world population," says Dr. Alcino Silva, professor of neurobiology, psychiatry and psychology at the David Geffen School of Medicine at UCLA. "Currently, there are no treatment options for these people. That's why our findings are so exciting from a clinical perspective."

Dr. Silva and colleagues focused their research on the most common genetic cause for learning disabilities: Neurofibromatosis type I (NF1) in the hope that through understanding this particular learning disability, which is caused by a single defective gene, development of effective and sustainable treatments might become possible.

Researchers then could use their findings to tackle the general class of learning and memory problems.

Because of the difficulties and limitations of studying mechanisms of memory in human patients, the researchers decided to study NF1 in mice.

Ras Molecule

In earlier research, mice with the mutations that cause NF1 in human patients were found to possess many of the features of this complex disorder, including deficits in spatial learning, attention and motor coordination.

Studies of these mutant mice showed that the learning deficits were caused by the overactivity of a molecule called Ras, causing an imbalance between signals that activate brain cells and those that inhibit them.

"The act of learning creates physical changes in the brain, like grooves on a record," explains Dr. Silva. "But surplus Ras tips the balance between switching signals on and off in the brain. This interrupts the delicate cell communication needed by the brain to record learned information."

The work reported by Dr. Silva and colleagues this week demonstrates that Lovastatin can reverse the overactivity of Ras, decrease inhibition, repair the cell-cell communication deficits, and cure the learning disabilities of the adult Nf1 mutant mice.

Complete Rescue?

These findings suggest that the disabling learning deficits associated with NF1 -- a disorder that affects one in three thousand people worldwide -- could be cured with a class of relatively safe drugs (statins) that millions of people have taken to lower cholesterol for extended periods of time over the last 20 years.

The findings also demonstrate that -- contrary to popular belief -- the cognitive deficits associated with this disorder are not irreversible, since a limited treatment in adult mice effectively reversed the condition. Because the mechanisms of NF1 function are similar in mice and men, these findings suggest that statins will be an effective strategy to treat NF1 in humans.

"This is mind-blowing -- we think we have a real fundamental reason to be optimistic," says Dr. Silva. "Here is a drug that affects a key learning and memory pathway, and completely rescues the most common genetic cause for learning disabilities. We don't have to do extensive clinical trials for toxicity or safety --these were already completed for other uses."

The results proved so hopeful that the Food and Drug Administration approved the use of the drugs in three clinical trials currently under review to test the effect of statins in children and adults born with NF1. The findings could help the estimated 35 million Americans who struggle with learning disabilities.