Study: Testosterone-linked molecule protects against MS in mice

January 31, 2018
A new study finds that a testosterone-induced molecule reverses harmful immune response and eliminates disease symptoms in female mice. Until now, scientists haven't understood how the hormone provides protection. The discovery may offer a new target for MS therapy for women.

Scientists at Northwestern Medicine used a mouse model of MS to identify a guardian molecule – triggered by testosterone – that appears to protect males from disease. When female mice with disease were treated with this protective molecule, their symptoms were eliminated. The discovery stemmed from an earlier lucky mistake in the lab in which male mice were used instead of female mice. 

Northwestern scientists showed that testosterone caused mast cells, a type of immune cell, to produce the guardian molecule, cytokine IL-33, in male mice. The guardian molecule triggers a cascade of chemicals that prevents the development of another type of immune cell, Th17 cells. These Th17 cells can directly attack and destroy the myelin. In the mouse-model of MS, females develop more of the disease-causing Th17 immune response than males. But that damaging response was reversed in females by treatment with IL-33.

Limited clinical trials in male MS patients have shown that testosterone treatment over 12 months can partially reverse evidence of myelin- and nerve-degeneration and alleviate symptoms. However, short-term testosterone administration is not a viable therapy for either men or women because of the many undesirable side effects.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers said the findings have identified new and more specific cellular and molecular targets for immune intervention that they hope will lead to better therapies.

The findings were published in the Proceedings of the National Academy of Sciences.

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