MS affects women two to three times more often than men. Pregnancy has a temporary beneficial effect on MS disease activity in women. Exploring these and other gender-related aspects and differences is bringing new insights about the course of MS and may lead to new therapies.
In 1998, the National MS Society targeted this area to fuel its potential for unraveling the mysteries of MS and developing new therapeutic strategies. In 2003, the initiative was declared to be a success in attracting investigators into this previously underserved area, in generating new data and in resulting in the expenditure of nearly $10 million in new research and training focused on sex-based issues that impact MS.
The Society’s gender initiative, which was funded by a special campaign, generated new information on sex differences in disease course, the immune system, brain tissues, hormonal influences, and response to infection, and significantly increased the body of scientists pursuing these questions in MS.
Here is a sample of studies recently funded by the National MS Society on this now-mainstreamed area of gender research:
- In the first effort of its kind in MS, Rhonda Voskuhl, MD (University of California, Los Angeles) is leading a team of investigators at 15 medical centers to conduct a two-year, controlled clinical trial of the oral sex hormone estriol added to standard therapy to treat MS. This study is based on a previous, smaller trial funded by the Society’s gender research initiative. Investigators are administering estriol along with glatiramer acetate or glatiramer acetate plus inactive placebo to 150 women with relapsing-remitting MS. If successful, this clinical trial could lay the groundwork for a larger, definitive trial that could lead to a new treatment option for women with MS. This study is being funded by the National MS Society in partnership with the Society’s Southern California chapter and the National Institute of Neurological Disorders and Stroke.
- Elizabeth P. Blankenhorn, PhD (Drexel University) is seeking to identify genes that are responsible for gender differences. Her team is taking a unique approach to try to separate the influences of genes versus hormones in mice with the MS-like disease EAE. Because of the similarities between the genetic material of mice and humans, the genes identified through this study will be directly testable in terms of their possible involvement in human MS. Previous research funded by the Society’s gender initiative identified a variation in a gene that controls a powerful immune messenger chemical called interferon (IFN) gamma. IFN gamma has been linked to immune attacks in MS, and these findings suggest that men have the gene variant that causes high levels of interferon gamma less often than women.
- Patrizia Casaccia, MD, PhD (UMDNJ-Robert Wood Johnson Medical School) is exploring how gender differences may impact the development of a novel strategy to repair tissue lost in MS. Because MS can destroy the insulating myelin that wraps nerve fibers and the nerve fibers as well, finding ways to repair myelin and protect the nerve fibers is crucial to recovery of normal neurologic function. One possibility is to find ways to stimulate adult stem cells that reside in the brain to repair damaged tissues. In her studies of mice, Dr. Casaccia has discovered that the number of stem cells in the brain is regulated by the function of a gene called p53 and is also differentially regulated by sex hormones and gender. Among her team’s experiments are attempts to enhance the ability of transplanted adult stem cells to survive and form myelin in the two sexes. If Dr. Casaccia-Bonnefil’s efforts are successful, it will provide potential ways to enhance myelin repair in MS and offer new information on why MS may have a very different disease course in men and women.
- Robert P. Skoff, PhD (Wayne State University) is defining differences in the cells that make myelin in males and females. Myelin insulates nerve fibers and is a prime target in MS. He hopes to determine whether differences in these cells, such as their response to sex hormones and capacity for rebuilding damaged myelin, play a role in why women are more susceptible to MS than men, and experience differences in disease course.