Common drug cures learning disability
* 17:00 07 November 2005
* NewScientist.com news service
* Gaia Vince
* Acino Silva’s lab at UCLA
* Neurofibromatosis Association, UK
* Current Biology
A cure for one of the most common forms of learning disability may be on the horizon, US researchers have revealed.
They reversed the condition in adult mice born with it, curing their learning disabilities by using a commonly prescribed drug. The researchers say the technique could potentially lead to treatments for other learning disabilities.
Neurofibromatosis type I (NF1) is a condition caused by a single gene defect that affects more than 1 in 3000 people. The defect is either inherited or caused by a spontaneous mutation, which can then be inherited.
NF1 causes developmental cognitive disabilities in up to half of those with the defective gene, including deficits in memory, motor coordination and spatial learning. It can also cause attention-deficit hyperactivity disorder (ADHD).
Previous mouse studies show the cognitive deficits result from the mutant gene causing over-production of a molecule called p21Ras. This leads to an imbalance between the signals that activate brain cells and those that inhibit them, creating problems in the cell-to-cell communication needed for learning.
Neurobiologist Alcino Silva and colleagues at the University of California, Los Angeles, US, tried a commonly prescribed cholesterol-lowering statin drug – called lovastatin – on adult mice with the NF1 mutation. In a series of experiments to test their cognitive functions, the team showed that the drug reversed the learning disabilities and brought the cognitive functions of the mice up to normal levels.
Silva says finding the drug “was the researcher’s equivalent of finding a suitcase stuffed with a million dollars”. Lovastatin actually reversed the over-production of Ras and repaired the cell-to-cell communication deficits, curing the mice's learning disabilities.
In one experiment, the mice had to follow a blinking light to get a food reward. The mice with the disorder showed a 30% improvement in their ability to pay attention when given the statin.
Another experiment showed that NF1 mice given the drug were able to out-perform normal mice in spatial memory tasks. The findings demonstrate that, contrary to current thinking, the cognitive deficits associated with NF1 are not irreversible developmental defects.
“We think we have a real, fundamental reason to be optimistic," Silva says. "This is a drug that affects a key learning and memory pathway, and completely rescues the most common genetic cause for learning disabilities.”
The statin works by blocking certain fats that Ras needs in order to function, Silva explains: “Ras needs lipids to be attached to the cell membrane where it acts – the lipids are like anchors. Lovastatin and other statins lower the lipids and, without anchors, Ras floats away from the membrane and becomes ineffective.”
Lovastatin already has a proven safety record, having been used by millions of people over extended periods during the last 20 years. The US Food and Drug Administration has approved the use of the drug in three clinical trials on children and adults born with NF1.
About 5% of the world’s population has a learning disability of some type and Silva claims that statins could potentially treat some of them, too. “The Ras pathway is central to memory and learning and I believe Ras is connected to either the problem or the solution in many other learning disabilities, directly or indirectly."
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