FDA-approved hypertension drug guanabenz prevents myelin loss and improves multiple sclerosis (MS) in lab animals.

This discovery was announced yesterday by scientists from the University of Chicago on the pages of Nature Communications..

They say that guanabenz activates a natural cellular mechanism that protects myelin-producing cells from the negative effects of the inflammatory process in MS..

“Guanabenz seems to affect the cell's own defense mechanism, slowing down the loss of myelin, the basis of the pathological process in multiple sclerosis.. Scientists have made many attempts to stimulate myelin repair, but this is a completely unique approach.. You don't have to focus on restoring myelin if the loss of myelin isn't already 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, the substance that coats nerve fibers.. Multiple sclerosis today affects more than 2.3 million people worldwide, and doctors still cannot cure this disease..

Professor Popko and colleagues have previously demonstrated that oligodendrocytes, the brain cells that produce myelin, have a natural defense mechanism that is activated in response to inflammation.. Cells temporarily almost completely stop the synthesis of normal proteins in order to selectively increase the synthesis of protective proteins. When this mechanism does not work or is already overloaded (for example, in chronic inflammation), oligodendrocytes die and demyelination continues..

A recent study showed that guanabenz enhances the cellular response to inflammatory stress.. Mechanisms of action of the drug, not related to its antihypertensive effect, are responsible for this effect.. To test the possibility of using guanabenz in the treatment of MS, Prof. Popko's group exposed a cell culture of oligodendrocytes to interferon gamma, causing inflammation, loss of myelin, and cell death..

The use of guanabenz prevented the loss of myelin and helped cells survive in aggressive conditions.. At the same time, guanabenz had no effect on oligodendrocytes that were not treated with interferon gamma.. This suggests that the drug will only work if inflammation is present..

The researchers then tested the drug in mice with multiple sclerosis.. Guanabenz protected against demyelination in genetically modified mice with increased levels of gamma-interferon in the brain. After the course of treatment, their brains had several times more myelin than their sick relatives from the control group who did not receive the drug..

For further study, Chicago scientists immunized healthy mice with a component of myelin, causing them to have an immune response to their own myelin that resembles multiple sclerosis in humans.. If such mice were given guanabenz one week after immunization, the symptoms of MS developed with a significant delay, and were less pronounced.. What’s more, 20% of the rodents showed no symptoms at all..

For the next experiment, the scientists took mice with symptoms of relapsing-remitting multiple sclerosis, and began to give them guanabenz for exacerbations of the disease.. Such therapy led to a decrease in the severity of symptoms by an average of 50% at the next exacerbation..

Researchers have confirmed that guanabenz temporarily blocks the reactivation of a protein called eukaryotic translation activating factor 2 (eIF2? When eIF2 is deactivated? initiates a cellular response to stress. If its reactivation is blocked, then it is possible to provide a long-term protective response of the cell to inflammatory stress and protect it from death..

The authors of the work say that the results of recent experiments, as well as a good safety profile of guanabenz, give hope that it can become a new therapeutic option for multiple sclerosis.. The Myelin Repair Foundation, which funded this work, will partner with the National Institutes of Health (NIH) to push for faster development and clinical trials of guanabenz in patients with relapsing-remitting MS..

“Probably, guanabenz will not be used as a monotherapy, but we hope that it will become one of the components of a new effective combination therapy.. Some of the drugs used today to treat MS have dangerous side effects, including on the brain.. There is an urgent need to create more effective and safer treatment for patients,” says Popko..

medbe. en.