A newly identified difference between the brains of women and men with multiple sclerosis (MS) may help explain why so many more women than men get the disease, researchers at Washington University School of Medicine in St. Louis report.
In recent years, the diagnosis of MS has increased more rapidly among women, who get the disorder nearly four times more than men. The reasons are unclear, but the new study is the first to associate a sex difference in the brain with MS.
The findings appear in The Journal of Clinical Investigation.
Studying mice and people, the researchers found that females susceptible to MS produce higher levels of a blood vessel receptor protein, S1PR2, than males and that the protein is present at even higher levels in the brain areas that MS typically damages.
“It was a ‘Bingo!’ moment– our genetic studies led us right to this receptor,” said senior author Robyn Klein. “When we looked at its function in mice, we found that it can determine whether immune cells cross blood vessels into the brain. These cells cause the inflammation that leads to MS.”
An investigational MS drug currently in clinical trials blocks other receptors in the same protein family but does not affect S1PR2. Klein recommended that researchers work to develop a drug that disables S1PR2.
MS is highly unpredictable, flaring and fading at irregular intervals and producing a hodgepodge of symptoms that includes problems with mobility, vision, strength and balance. More than 2 million people worldwide have the condition.
In MS, inflammation caused by misdirected immune cells damages a protective coating that surrounds the branches of nerve cells in the brain and spinal column. This leads the branches to malfunction and sometimes causes them to wither away, disrupting nerve cell communication necessary for normal brain functions such as movement and coordination.
For the new research, Klein studied a mouse model of MS in which the females get the disease more often than the males. The scientists compared levels of gene activity in male and female brains. They also looked at gene activity in the regions of the female brain that MS damages and in other regions the disorder typically does not harm.