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Cholesterol Drug May Help Learning Disabilities

Posted on: Thursday, 10 November 2005, 06:00 CST

By Thomas H. Maugh II

Lovastatin, a widely used cholesterol-lowering drug, reverses common learning disabilities in mice, offering the first hope for a treatment of the problem in humans, University of California, Los Angeles researchers reported Monday

Three separate human trials in both children and adults will begin at UCLA and other U.S. and European locations within weeks, said Dr. Alcino J. Silva, a neurobiologist at UCLA and the lead author of a paper appearing in the journal Current Biology.

"Currently, there are no treatment options for these people," Silva said. "That's why our findings are so exciting from a clinical perspective."

Lovastatin, trade-named Mevacor, is one of a family of drugs known collectively as statins that have revolutionized the treatment of high cholesterol. The drugs, first introduced in the 1990s, are taken daily by millions of people at risk for heart disease and other problems, and have been widely recognized as safe.

The learning problems studied by the researchers were caused by a genetic defect called neurofibromatosis 1, the most common genetic cause of learning disabilities. It affects one in every 3,000 to 4,000 people.

The learning disabilities include poor attention spans, difficulties in carrying out tasks involving spatial abilities, and problems learning new tasks.

The treatment also may be useful in a much larger group of people because the underlying molecular disorders in other types of learning disabilities may be similar, Silva said. As much as 5 percent of the population is learning disabled, and lovastatin may be useful in treating many of them, he said.

"We cannot demonstrate it rigorously, but we have many reasons to believe that it is very promising for these other categories as well," he said.

The key to the discovery is a protein called Ras, which regulates how brain cells communicate.

Silva and his colleagues had previously shown that the genetic mutations associated with neurofibromatosis 1 lead to an excess production of Ras, which inhibits the brain's ability to record newly-learned information.

The team searched for a drug that could interfere with the excess Ras, but had little success, Silva said. Then one of his ex- students, Steve Kushner, learned during a medical school rotation that statins can interfere with Ras.

"He came back into my office late at night and said, I think I have something that might work,' " Silva said.

Statins interfere with Ras by reducing the level of fats found in blood, known as lipids, which are required by Ras to carry out its function.

Postdoctoral fellow Weidong Li in Silva's lab tested the theory using specially bred rats that have the neurofibromatosis 1 mutation and have previously been shown to have learning problems similar to those seen in humans with the disorder.

In one test, he trained adult mice with the mutation to follow a blinking light to obtain a food reward. After the animals received the drug, their performance improved 30 percent so that they outperformed normal mice. Two other tests provided similar results.

"This is mind-blowing," Silva said. "We think we have a real, fundamental reason to be optimistic. ... Now we are ready to go and treat the human disorder."

Source: Cincinnati Post

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