A hypertension medication may prevent myelin loss and alleviate clinical symptoms of multiple sclerosis (MS) based on a study in animal models, according to newly published research in the journal Nature Communications.
In prior research, Brian Popko, PhD, of the University of Chicago, and colleagues found that oligodendrocytes respond to stressors like inflammation and temporarily shut down nearly all normal protein production in the cell and increase the production of protective proteins in a discerning manner. Oligodendrocyte death and demyelination is significantly increased when this mechanism is faulty by chronic inflammation seen in diseases such as MS. The hypertension drug guanabenz has shown to enhance the stress response pathway independent of its anti-hypertension mechanism of action.
The researchers first exposed cultured oligodendrocyte cells to interferon gamma, which led to greatly increased myelin loss and cell death. This loss was prevented when the cells were treated with guanabenz and the cell survival was restored to near normal levels. Oligodendrocytes not exposed to interferon gamma were not impacted by guanabenz, which suggests that it enhances only an active stress response pathway. Mice that were genetically engineered to produce high levels of interferon gamma and treated with guanabenz were protected against oligodendrocyte and myelin loss; they also retained more myelination and oligodendrocytes vs. untreated mice.
After mice were immunized with a component of myelin, an immune response against myelin similar to MS in humans was triggered. While clinical symptoms developed, guanabenz significantly delayed the onset of symptoms when administered a week following immunization and reduced peak severity. Guanabenz also reduced the risk of any symptom development by about 20%. When guanabenz was administered immediately after symptoms peaked, severity during the next relapse cycle was lowered by nearly 50%.
Guanabenz is a centrally acting beta-2 adrenergic agonist indicated for treatment of hypertension. The authors suggest that guanabenz stimulates a “protective cascade” that leads to a decreased inflammatory response and myelin level preservation.
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