Undoing Learning Disability

Treatment with a commonly prescribed cholesterol-lowering drug reverses learning disability in a mouse model of the disorder, according to researchers at the University of California, Los Angeles (Curr. Biol. 2005, 15, 1961). “This is mind-blowing,” declares neurobiologist Alcino J. Silva. The drug “completely rescues the most common genetic cause for learning disabilities.”

Silva, along with postdoc Weidong Li and colleagues, worked with a mouse model of neurofibromatosis type 1 (NF1). The disorder results from mutations in the gene for neurofibromin. Neurofibromin helps regulate Ras. This protein, which requires fat to function, is involved in communication between brain cells. The mutations associated with NF1 increase Ras activity and interfere with this intercellular communication, leading to learning difficulties.

Aware that Ras had been suggested as a therapeutic target for treating NF1 and that lovastatin can inhibit Ras activity, the UCLA researchers put the two ideas together and tested the drug in NF1 mice. They found that lovastatin reversed the cognitive deficits of the mice to such a degree that some of the treated animals performed better than normal mice. The results showed that, contrary to popular belief, “these deficits are not due to irreversible developmental changes,” the team notes.

Kathryn North, a University of Sydney neurologist and geneticist who has written about NF1, says the work shows that lovastatin is “an exciting potential therapy for patients with NF1, the main limitation being that we do not know whether the cognitive phenotype seen in the mouse truly represents what we see in humans.”

The utility of statins in humans will become clearer because the Food & Drug Administration has approved clinical trials of the drugs in children and adults born with NF1.