Discovering Sex Differences in Multiple Sclerosis
From an early age, Dr. Shannon Dunn was struck by the fact that multiple sclerosis (MS) was a disease that preferentially affects women. Her mother and four other women she knew from her hometown of Sudbury in Northern Ontario were diagnosed with the disease.
Now, as a newly named Sex and Gender Science Chair supported by the Canadian Institutes of Health Research, Dunn will have the opportunity to study how sex impacts the immune system and development of autoimmune diseases like MS.
Dunn is an associate professor of immunology at the University of Toronto and a scientist in the Keenan Research Centre for Biomedical Science at Unity Health Toronto. She recently spoke with writer Ciara Parsons about her research.
How did you become interested in research on the causes of MS?
I got involved in this research because my mom was affected by MS. She suffered from this disease before effective treatments were available. As a youth, I knew several other women diagnosed with MS, but only one man. So, it seemed to me, even before I became a scientist, that MS affected women at a higher rate than men. Being a child of an MS patient, I also knew that I was at greater risk of developing MS, so naturally I was interested in learning more about why this disease affects some people but not others.
When I completed my PhD studies, I began looking for postdoctoral opportunities and decided to pursue a position with Dr. Larry Steinman at Stanford University. At the time, he was making discoveries that were leading to new MS therapies and I was really attracted to how he modeled the disease process in the lab and was able to translate these findings to new MS therapies.
MS is a chronic illness that affects the central nervous system, but what role can an autoimmune response play in its development?
MS is considered to be autoimmune disease where the immune system attacks and destroys myelin, the fatty substance that protects nerve fibres in the brain. Although we still do not yet understand how MS gets started in individual people, past research has identified a number of risk factors that operate at the population level to increase MS. By better understanding how these MS risk factors alter autoimmune processes, we can get a better understanding of how the disease gets started. This is where my work comes in.
Can you tell us a bit about the new CIHR funding and the work it will support?
The agency has provided $700,000 over a four-year term to investigate the sex differences related to MS, through a series of studies. The first study will examine how the onset of puberty changes the immune system and how this can accelerate the development of an MS-like disease in mice.
In the second study, we will be examining how the immune system is different in a female and male after puberty and how this contributes to sex differences in the development of this disease. In a third study, we will specifically evaluate the effect of ovarian function in women on the immune system. This latter study will be collaboration with Dr. Gillian Einstein, who has been studying possible effects on cognition among women who have opted to remove their fallopian tubes and ovaries to limit their genetic risk for cancer. Together, these studies will provide important insights into how the immune system is different between a male and female and how sex and ovarian functioning alter the immune system in a way to make a disease like MS initiate more readily in a female.
Are there specific differences in how MS manifests in women and men?
MS does look the same in male and female patients, but men typically reach certain disability landmarks, such as needing a cane or requiring a wheelchair, more quickly than women. Therefore, although men are less vulnerable to acquiring MS, they may be on a more severe trajectory for the disease. We don’t quite understand yet how or why this happens. We are conducting exploratory studies using immune samples that we have collected from female and male patients to support immune studies to get insights into why males may acquire a more aggressive form of this disease.
Canada has some of the highest rates of MS in the world, and some research hypothesizes that environmental factors may be a factor here. Will your research look at that possibility?
One of the factors that may contribute to Canada’s high rates of MS is that we live at a higher latitude and therefore are exposed to lower levels of sunlight and make less vitamin D than those living closer to the equator. Other researchers have looked at the interaction of sex with vitamin D metabolism and found vitamin D is a protective factor against MS. Research in lab models has shown that vitamin D has a protective effect against autoimmunity more so in females. So, lower levels of vitamin D may be one factor that accounts for the high rates of MS in Canadian women.
Another potential environmental risk factor is the development of adolescent obesity. In my research in lab models of MS, I’ve found that adolescent obesity enhances an MS-like disease especially in females. In the obese state, myelin reactive T cells are more pro inflammatory and cause more severe tissue damage in females compared to males. Therefore, the rising incidence of childhood obesity could be an additional reason for why the incidence of MS is rising in North America and in Europe.
What do you hope to accomplish with the new funding from CIHR?
This Chair will fund these projects and a new cohort of trainees who will specifically work in this important area. The ultimate goal of this research is to provide important new insights into the underlying reasons for sex differences immunity and autoimmunity. This Chair will also provide me with a platform to educate researchers in the general public about the importance of studying biology in both males and females. I hope to convince researchers that you can sometimes learn twice as much by studying the similarities, or alternatively, the differences, between the sexes.
