New Study Explains why MS Affects more Women
MS affects women almost four times more often than it affects men. The reasons are unclear, but a new study is the first to associate a sex difference in the brain with MS. The newly identified difference between the brains of women and men with multiple sclerosis (MS) offer not only insight into why, but also may offer a course of treatment.
Looking at mice and people that have MS, 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, MD, PhD. “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.”
For those unfamiliar with MS it is a autoimmune disorder that causes the myelin sheath [the coating around nerves] to be destroyed which leads to scarring and inflammation. MS can flare, at certain times a person might seem normal and at other times might have problems with mobility, vision, strength and balance. More than 2 million people worldwide have the condition.
In the new research, Klein studied the 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, then they looked at regions the disorder typically does not cause any damage.
Then they identified 20 genes that were active at different levels in vulnerable female brain regions. [It is interesting to note that scientists don’t know what 16 of these genes do.] Out of the remaining genes, the increased activity of S1PR2 stood out because researchers knew from previous studies that the protein regulates how easy it is for cells and molecules to pass through the walls of blood vessels.
Additional experiments showed that S1PR2 opens up the blood-brain barrier [or the BBB], a structure in the brain’s blood vessels that tightly regulates the materials that cross into the brain and spinal fluid [the BBB makes it equally difficult for medicines to cross over and be effective in treatments, which can sometimes hinder a drugs effectiveness].
This barrier normally blocks potentially harmful substances from entering the brain. Opening it up likely allows the inflammatory cells that cause MS to get into the central nervous system.
So what’s next? Researchers plan on designing a tracer that will allow them to monitor the S1PR2 levels in the brains of people while they are living. She hopes that this will lead to a better understanding of how S1PR2 effects people with MS and even possibly develop a better targeted treatment for people suffering from MS.
Already know that the hippocampus is more than just where hippos go to school? You probably want the full study, which can be found — here!
Cruz-Orengo L., Daniels B.P., Dorsey D., Basak S.A., Grajales-Reyes J.G., McCandless E.E., Piccio L., Schmidt R.E., Cross A.H. & Crosby S.D. & (2014). Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility, Journal of Clinical Investigation, DOI: 10.1172/JCI73408DS1