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Statins aid slow learners

November 8, 2005 By Roxanne Khamsi This article courtesy of Nature News.

Cholesterol-busting drugs help mice with learning disability.

There's a new lesson to be learned about statins, a class of widely prescribed drugs that lower cholesterol. A study in mice suggests that this type of medication could reverse a learning disorder known as neurofibromatosis.

The disorder, also called NF1, affects about 1 in every 4,000 children and can cause learning disabilities, coordination problems and benign tumours that grow on nerve tissue.

Researchers have found that mutations in a single gene are to blame for NF1. The affected gene fails to produce a protein called neurofibromin, which normally keeps another protein, Ras, in check. Evidence from mouse studies suggests that an overabundance of active Ras results in abnormal nerve-cell responses in the brain.

He came to my lab at one in the morning and said 'I think I have a solution'.
Alcino Silva
University of California Los Angeles
Ras also requires cholesterol compounds to function, and this led medical student Steven Kushner to wonder whether cholesterol-busting drugs could keep Ras in check, should neurofibromin not be up to the task.

Kushner stumbled on the idea after learning about statins while on a clinical rotation. "He came to my lab at one in the morning and said 'I think I have a solution'," says his supervisor, Alcino Silva of the University of California, Los Angeles.

Silva's group went on to test the idea in mice, and report the encouraging results in Current Biology this week1.

Seeing the light

Mice genetically engineered to have the same defect as NF1 humans have a hard time focusing their attention on a task. In one test, for example, mice are exposed to a blinking light that appears consistently either to their left or right. If the mice learn to look in the right direction, they are rewarded for spotting the blinking light with food.

Mice with NF1 only learn to watch the right spot 50% of the time. But those given statins up their learning rate to about 65% of the time. That's a 30% improvement in their ability to pay attention, the team reports.

Similarly, NF1 mice trained to find a dry platform in a water maze were 4 seconds faster on their fifth day of training if they had received a dose of statins.

Trial runs

The results of the recent experiment "strongly suggest that this pharmacologic approach may be an effective way to treat the learning disabilities in children with NF1", says David Gutmann, director of the Neurofibromatosis Center at Washington University in St Louis, Missouri. But he stresses that other drugs currently in trials for the treatment of NF1-associated tumours may also be useful for improving cognitive function in these people.

Silva points out that statins offer one distinct advantage over other drug options: people have taken these tablets for nearly two decades without toxic side effects. "We know these drugs are sustainable," he says.

Researchers have received approval for three clinical trials to see if statins can reverse NF1-related learning disabilities in people. Two trials will start shortly in the United States, the third in the Netherlands. "We should know in one to two years if it works or not," says Silva.


  1. Li W., et al. Curr. Biol., 15. 1961 - 1967 Doi:10.1016/j.cub.2005.09.043 (2005).

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