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Recreating 'Flowers for Algernon' with a happy ending

"We thought, 'Wouldn't it be nice to find a drug that is already FDA-approved, safe for lifetime use and could be tested in mice and humans with NF1?' Fortunately, our optimism was rewarded."

It took a medical student in Silva's lab to identify the drug and connect it with NF1. Steve Kushner, a scholar in UCLA's MD/PhD program, learned in a clinical rotation about statins, the drugs already prescribed to millions of people worldwide to lower cholesterol.

"Steve raced into my lab and shared what he'd learned: statins work on the Ras protein that is altered by NF1 and play a key role in learning and memory," recalled Silva. "It was the researcher's equivalent of finding a suitcase stuffed with a million dollars."

Statin drugs lower cholesterol by blocking the effects of certain fats. Because Ras requires fat to function, less fat results in less Ras. With reduced Ras activity, the brain cells are able to communicate properly in mice with NF1, allowing normal learning to take place.

"NF1 interrupts how cells talk to each other, which results in learning deficits," said Silva. "Statins act on the root of the problem and reverse these deficits. This enables the process of learning to physically change the brain and create memory."

Silva's lab tested the effects of statins on mice that were bred with the NF1 mutation. The animals displayed the same symptoms as people with NF1: attention deficits, learning problems and poor physical coordination.

First author Weidong Lee, a UCLA postdoctoral fellow, ran three tests to compare the behavior of NF1 mice treated with statins to NF1 mice who received a placebo. Then he compared both groups to normal mice.

First, he trained the mice to follow a blinking light in order to find a food reward. The NF1 mice on statins showed a 30 percent improvement in their ability to pay attention, outperforming the normal mice.

Second, he trained the mice t
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Source:University of California - Los Angeles


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