A drug normally used to treat hypertension reduced the symptoms of multiple sclerosis in mice models of the disease.
Multiple sclerosis (MS) in animal models can be alleviated using a US Food and Drug Administration (FDA) approved medication for high blood pressure, according to research published in Nature Communications.
The high blood pressure drug, guanabenz, was found to prevent myelin loss and to reduce the clinical symptoms of MS in the animal models, according to the researchers from the University of Chicago Medical Center who conducted the investigation. The drug seemed to enhance the innate cellular mechanism that protects myelin producing cells against inflammatory stress, which the researchers believe can blaze the path to new therapeutics to combat MS.
“Guanabenz appears to enhance the cell's own protective machinery to diminish the loss of myelin, which is the major hallmark of MS,” explained senior study author Brian Popko, PhD, in a press release. “While there have been many efforts to stimulate remyelination, 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.”
Prior research conducted by the team has demonstrated that oligodendrocytes, the brain cells that in tasked with producing myelin, respond to inflammation by shutting down normal protein production and selectively increasing the production of protective proteins. In MS, there is chronic inflammation due to the oligodendrocyte death. Then, demyelination is significantly increased.
Guanabenz, which is approved by the FDA for oral administration in the treatment for hypertension, enhanced the stress response outside of its anti hypertension functions. The authors of the study tested cultured oligodendrocyte cells when they were exposed to interferon gamma (a molecule which increases inflammation). The results showed greatly increased myelin loss and cell death. However, when the oligodendrocyte cells which were not exposed to interferon gamma were treated with guanabenz, myelin loss was prevented and cell survival was restored to normal levels. The oligodendrocyte cells not exposed to interferon gamma were unaffected by treatment with guanabenz, which the researchers hypothesized indicated that it enhances only an active stress response pathway.
When the researchers tested the effects of guanabenz on mouse models of MS which had relapsed, they found a nearly 50 percent reduction in severity during the following relapse cycle.
“Guanabenz will probably not be a standalone drug, but we hope that it can be developed for use in combination with other medications,” Popko concluded. “Some current treatments can have severe side effects — for example dangerous infections in the brain. It would be of tremendous benefit for patients to have effective, less risky therapies.”