lovastatin and attention-deficit hyperactivity disorder (ADHD) .

William Wagner · medicine forum Guru Joined: 29 Apr 2005 Posts: 809

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Common drug cures learning disability

€ 17:00 07 November 2005
€ NewScientist.com news service
€ Gaia Vince

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.

Above average
Silva says finding the drug ³was the researcher¹s equivalent of finding
a suitcase stuffed with a million dollars². 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.
Fatty anchors
³We 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.²
The statin works by blocking certain fats that Ras needs in order to
function, Silva explains: ³Ras 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.²
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 world¹s population has a learning disability of some
type and Silva claims that statins could potentially treat some of them,
too. ³The 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."
Journal reference: Current Biology (vol 15, p1961)

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