Commonly used to lower “bad” cholesterol, statins are also effective at reversing learning disabilities caused by a genetic mutation, according to a new mouse trial.
Noonan syndrome is a developmental disorder that causes unusual facial features, stunted growth and heart problems. About half of all people with Noonan also have learning deficits.
The syndrome affects 1 in 2,000 people, and no treatment currently exists.
The new study, published in Nature Neuroscience and conducted by researchers at the University of California-Los Angeles (UCLA), claims to identify not only the mechanism causing the disease, but also a treatment for it.
A variety of genetic factors contribute to Noonan syndrome, but a single gene – which encodes for a protein that regulates the protein Ras – causes about half of all cases.
The UCLA team found that the mutated gene implicated in Noonan syndrome creates hyperactive Ras. Because Ras regulates communication between brain cells, this surplus Ras has a disruptive effect on brain cell communication, damaging the learning process.
“The act of learning creates physical changes in the brain, much like grooves on a record,” explains principal investigator Alcino Silva, professor of neurobiology, psychiatry and psychology at the David Geffen School of Medicine at UCLA. “Surplus 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.”
“An overabundance of Ras prematurely alters the brain’s synapses, leaving no place for the brain to record the changes necessary for learning,” adds first author Young-Seok Lee.
- In some patients with Noonan syndrome, growth hormone has been used successfully to treat the short height characteristic of the condition
- Other physical symptoms include down-slanting or wide-set eyes, low-set or unusually shaped ears, sagging eyelids, small penis and undescended testicles in males, sunken chest shape and webbed or short-appearing neck
- Noonan syndrome is an autosomal dominant condition, which means only one parent has to pass down the mutated gene for their child to have the syndrome.
In a mouse model genetically engineered to have Noonan syndrome, Silva and colleagues attempted to reverse this communication disruption. Basing their approach on Silva’s previous work in the Ras-linked disease neurofibromatosis 1, the team treated the mice with the common statin drug lovastatin.
Silva explains the thinking that led the team to statins:
“Noonan syndrome interferes with the changes in brain cells needed for learning, which results in learning deficits. 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.”
The researchers used mazes and objects to test the memory and cognitive ability of the mice. They found that the mice who had been treated with lovastatin had a drop in Ras activity and a corresponding improvement in their ability to navigate mazes and remember objects.
Silva says that the team was “amazed” to see cognitive function in the adult mice restored to normal, as “science assumes that therapy needs to start in the fetal stage to be effective.”
Therefore, the team’s findings suggest that the gene mutation not only affects development, but it also continues to impair adult brain function.
Next, the team will conduct clinical trials of lovastatin as a treatment for Noonan syndrome.