If it works in humans, it could be the first drug to alleviate mental retardation
and learning disabilities, the researchers said.
The Nov. 8 issue of the research journal Current Biology reports the
findings.
The researchers bred mice bred to develop the disease, called neurofibromatosis 1
(NF1), which affects an estimated one in 3,000 people.
The results proved so hopeful, they said, that the U.S. Food and Drug Administration approved the use of the drugs in three clinical trials currently under review to test their effect in
people with
NF1.
If scientists understand this learning
disability, they may be able to use the information to tackle a wide range of learning and memory
problems, the researchers said.
“Learning disabilities and mental retardation each affect five percent of the world population,” said Alcino
Silva of the University of California, Los Angeles, lead author of the study. “Currently, there are no treatment options for these people. That’s why our findings are so exciting.”
At least one condition that can cause learning
difficulties, Attention Deficit Hyperactivity Disorder, is already treatable.
But doctors generally classify it as a problem with attention or behavior rather
than a learning disability itself.
Silva and his colleagues had previously linked NF1’s learning problems to a
molecule called Ras, a protein that regulates how brain cells talk to each other
so that learning to take place.
The NF1 mutation creates hyperactive Ras
molecules, the researchers said. This disrupts cellular conversation and undermines the learning process.
“Learning creates physical changes in the brain, like grooves on a record,” said Silva.
Overactive 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.”
A popular class of drugs called Statins, which lower levels of artery-clogging
cholesterol in the blood, work by blocking the effects of certain fats.
Because Ras requires fat to function, less fat results in less
Ras, allowing normal learning to take
place, Silva said.
“NF1 interrupts how cells talk to each other, which results in learning deficits,”
he explained. “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 bred with the NF1 mutation. They
displayed the same symptoms as people with NF1: attention deficits, learning problems and poor coordination.
The NF1 mice on statins showed a 30 percent improvement in their ability to pay attention, outperforming normal mice,
the researchers said. The treated mice also beat normal mice on a maze test.
“Here is a drug that affects a key learning and memory pathway, and completely rescues the most common genetic cause for learning
disabilities,” Silva said. “We don’t have to do extensive clinical trials for toxicity or safety – these were already completed for other uses.”
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