How testosterone protects men from multiple sclerosis
Multiple sclerosis (MS) is a devastating degenerative disease with no known cure. A big mystery surrounding the disease is why it seems to affect women more than men, but new research from Northwestern Medicine may have finally discovered the reason. A guardian molecule has been found to protect against the disease, and it turns out it's triggered by testosterone.
MS is three to four times more likely to develop in women than men and while scientists have for some time suspected testosterone is a major factor, they haven't understood the underlying mechanisms. The new discovery began, like many wonderful research revelations, with a laboratory mistake. A graduate student accidentally used male mice in an experiment instead of female mice.
MS is an autoimmune disease where the immune system overproduces a type of immune cell called Th17, which attacks a membrane called the myelin sheath. The membrane protects the nerve axons found in the brain and spinal cord and when it's damaged, major irreversible symptoms such as cognitive deficits and a loss of motor function result.
In the new Northwestern study the researchers found that, in male mice, testosterone was resulting in the production of a molecule called cytokine IL-33, which was seen to trigger a pathway that prevented the production of Th17. When the researchers treated female mice with IL-33 the damaging effect of Th17 on the myelin sheath was effectively reversed.
"Because testosterone levels are seven-to-eight times lower in adult women compared to men, we speculate there are insufficient levels in females to activate this protective pathway," says Melissa Brown, lead author on the study. "But we showed we can activate the pathway with the guardian molecule, IL-33."
Interestingly enough, the researchers note that although the disease has been shown to develop in women at a young age, the development of the disease in men tends to correspond with an age-related decline in testosterone levels. Small human trials have also shown that testosterone treatment in men does partially alleviate symptoms, but there are significant side effects for both men and women, meaning it isn't particularly viable as a treatment.
The hope Northwestern researchers now have is that discovering this new specific pathway will allow more targeted therapies to be developed. It's also suggested that this testosterone-driven protective pathway could be a culprit in other autoimmune diseases that are seen more prominently in women over men.
The research was published in the journal Proceedings of the National Academy of Sciences.