A team of researchers led by individuals at Baylor College of Medicine (BCM) discovered a mutation in a gene involved with cholesterol synthesis with a Rett Syndrome mouse model. Rett Syndrome is a neurological disorder with autism symptoms. The BCM research team discovered a treatment with a cholesterol-lowering statin drug that has the ability to lengthen the lifespan and improved some symptoms of this syndrome in mice.
According to Dr. Monica Justice, professor of molecular and human genetics at BCM, “Treatments that affect cholesterol levels may have a role in treatment of patients with Rett Syndrome.”
The defective protein MECP2 affects mostly young female infants between the age of 6 to 18 months. These infants begin to regress and their growth development begins to slow. Abnormal hand motions develop such as wringing, movement becomes difficult and they lose the ability to speak. Autism-like symptoms also begin to develop. The mouse model without MECP2 shows similar symptoms.
These researchers identified 5 suppressor genes, however, one gene in particular that codes for squalene epoxidase stood out. This enzyme initiates the committed cholesterol pathway.
Justice reports that, “This stop codon mutation in squalene epoxidase down regulates the cholesterol pathway.” This stop codon prevents the message in RNA from being translated into protein. They also discovered that the mutation in this gene disturbs the synthesis of cholesterol in the brain initially and then eventually disrupts the whole system. According to Justice, “This stop codon mutation in squalene epoxidase down regulates the cholesterol pathway.”
Statin drugs generally have side effects. Individuals often experience memory loss as well as other problems. As a result, these drugs have not been demonstrated to to be beneficial in Alzheimer’s disease. However, Justice and her colleagues may have found a use for statin drugs in relation to the Rett Syndrome issue.
It turns out that if a person’s body has too much cholesterol, it will store it as fat. The brain contains high concentrations of cholesterol, but if it has too much, the brain stops production. Dr. Justice and her team of researchers believe that the mutation in squalene epoxidase and the statins keep the cholesterol pathway from peaking, creating a shutdown.
Justice goes on further to say, “The brain has to turn over the old cholesterol to the body’s periphery (outside the brain). When it does, it ‘talks’ to the liver and gut and tells them what is going on with cholesterol in the brain. We found that these mice were building up lipids (fats) in the liver.” Under normal conditions, the body stores fat in adipose tissue, not the liver. Justice also reports that, administering statin improve motor symptoms in mice as well as reducing cholesterol levels in the body. However, statin is not a cure. Statin doesn’t have the ability to affect breathing problems or the characteristic behavior of being startled in response to sound.
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