A protein “gatekeeper” that decides what gets past the blood-brain barrier is more prevalent in women than in men.

A newly discovered difference between male and female brains might hold the key to why more women than men are diagnosed with multiple sclerosis (MS).

Researchers at the Washington University School of Medicine in St. Louis noticed that a protein called S1PR2, which controls the permeability of the blood-brain barrier (BBB), is more prevalent in those with MS. Further exploration on both mice and humans revealed that, among people diagnosed with MS, women produced far more of this protein than men.

It’s a fact that more women than men are diagnosed with MS, but the reason why has left scientists scratching their heads. According to the National Multiple Sclerosis Society, “MS is at least two to three times more common in women than in men, suggesting that hormones may also play a significant role in determining susceptibility to MS. And some recent studies have suggested that the female to male ratio may be as high as three or four to one.”

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This study is the first to reveal a physical difference between the brains of male and female MS patients, but hormones did not appear to play a role in their findings, said senior author Dr. Robyn Klein, in an interview with Healthline. “In our animal studies, estradiol (a sex hormone) did not change levels of S1PR2,” she said. “However, there are more studies to be done.”

Klein and her team studied mice with a disease that resembles MS. Like MS, this disease affects female mice more frequently than it does males. Their study examined gene activity in the regions of the brain typically damaged by MS and compared it with areas normally untouched by the disease.

They identified 20 genes that are active in the disease. The function of 16 of those genes is still unknown. Of the remaining four, S1PR2 stood out. In earlier experiments, they had observed that the protein controlled how easily cells or molecules passed through the BBB.

“It was a ‘Bingo!’ moment—our genetic studies led us right to this receptor,” said Klein in a press release. “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.”

“The BBB has proteins that zip up all intercellular junctions,” Klein told Healthline. “S1PR2 causes junctional proteins to unzip,” allowing immune cells to pass through in MS. Once across the BBB, the immune cells are free to damage the myelin coating of nerves in the brain and spinal cord.

For their study, Klein’s team used donated brain tissue from MS patients who had passed away. For obvious reasons, examining the brains of live patients presents a unique challenge.

In order to further her research, Klein is working with chemists to design a “tracer” that can attach to S1PR2 and identify it using positron emission tomography, or PET scans. That way, living MS volunteers can undergo these scans and the tracer will light up areas where S1PR2 is active.

By examining S1PR2 in living patients, Klein hopes her team can better understand the protein’s role in MS. This could lead to new and better ways to treat the disease. If you can control the “gatekeeper” of the BBB, immune cells might not be able to cross over and do damage.

None of the current MS therapies on the market target this particular protein.