March 13, 2015
An FDA-approved drug for high blood pressure, guanabenz, prevents myelin loss and alleviates clinical symptoms of multiple sclerosis (MS) in animal models, according to a new study. The drug appears to enhance an innate cellular mechanism that protects myelin-producing cells against inflammatory stress. These findings point to promising avenues for the development of new therapeutics against MS, report scientists from the University of Chicago in Nature Communications on Mar. 13.
“Guanabenz appears to enhance the cell’s own protective machinery to diminish the loss of myelin, which is the major hallmark of MS,” said senior study author Brian Popko, PhD, Jack Miller Professor of Neurological Disorders at the University of Chicago “While there have been many efforts to stimulate re-myelination, this now represents a unique protective approach. You don’t have to repair the myelin if you don’t lose it in the first place.”
Multiple sclerosis is characterized by an abnormal immune response that leads to inflammation in the brain and the destruction of myelin – a fatty sheath that protects and insulates nerve fibers. MS is thought to affect more than 2.3 million people worldwide and has no known cure.
Popko and his colleagues have previously shown that oligodendrocytes, the brain cells which produce myelin, possess an innate mechanism that responds to stressors such as inflammation. It temporarily shuts down almost all normal protein production in the cell and selectively increases the production of protective proteins. When this mechanism is malfunctioning or overloaded – by the chronic inflammation seen in MS, for example – oligodendrocyte death and demyelination is significantly increased.
A recent study found evidence that guanabenz, a drug approved for oral administration for hypertension, enhances this stress response pathway independent of its anti-hypertension actions. To test the suitability of guanabenz as a potential treatment for MS, Popko and his team exposed cultured oligodendrocyte cells to interferon gamma – a molecule that increases inflammation – resulting in greatly increased myelin loss and cell death.
Treating these cells with guanabenz prevented myelin loss and restored cell survival to near normal levels. Oligodendrocytes that were not exposed to interferon gamma were unaffected by guanabenz, suggesting that it enhances only an active stress response pathway.
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