Females are about three times more likely than males to develop relapsing-remitting multiple sclerosis. Yet males who develop MS tend to experience faster neurodegeneration and accumulation of disability.
Why?
A new published study led by Accelerated Cure Project for MS (ACP) Chief Scientific Officer Stephanie Buxhoeveden, PhD, and a team of collaborators is exploring some of the biology that may help explain these differences.
Published in Biological Research for Nursing, the study examined microRNAs, or miRNAs — tiny molecules that help regulate the activity of genes involved in processes including immune responses and nervous system function.
Using blood samples from the ACP Repository, the team compared miRNA activity in males and females with newly diagnosed, untreated relapsing-remitting MS, as well as males and females without MS.
Looking for biological clues
Buxhoeveden and her fellow researchers found distinct patterns of miRNA activity in males and females with MS, including differences involving molecules associated with immune regulation and inflammation.
But one of the most interesting findings came from looking at people without MS.
Some of the immune-related differences between males and females were already present in the healthy control group. That suggests these biological differences may exist before MS develops, and that changes associated with MS may interact with underlying differences in how the immune systems of men and women are regulated.
The team also identified potential new avenues for investigation. Among them was miR-941, a microRNA that has received little attention in MS research but showed a consistent pattern in females with MS.
Because this was a small exploratory study, the findings will need to be validated in larger and more diverse groups. But they add to growing evidence that biological sex is an important variable in MS research and could ultimately help researchers develop better biomarkers and more personalized approaches to understanding and treating the disease.
Building on a larger body of research
The new study is part of a broader line of research by Buxhoeveden and her collaborators investigating the biological mechanisms that may contribute to differences in MS between males and females.
In an earlier review of the field, the team examined evidence involving genetics, hormones, environmental exposures and epigenetics — changes that affect how genes work without changing the underlying DNA sequence. That work highlighted miRNAs as particularly promising because they may help connect genetic, hormonal and environmental influences with the inflammatory and neurodegenerative processes involved in MS.
The review also identified studying miRNAs alongside messenger RNA, or mRNA, as an important next step. Additional work by Buxhoeveden and her collaborators examining mRNA is coming soon, continuing to build a more complete picture of the biological pathways that may contribute to sex differences in MS.
A research resource built for questions we haven’t asked yet
More than two decades ago, ACP launched the Repository, inviting people affected by MS and related conditions to contribute biological samples and health information that could support research for years to come.
Today, those contributions are still making an impact.
For the newly published miRNA study, Buxhoeveden and her collaborators were able to identify Repository samples from men and women with MS who were newly diagnosed and had not yet begun disease-modifying treatment. That gave the team a valuable opportunity to study early disease biology without the potential influence of MS medications.
When participants contributed those samples, they couldn’t have known all the questions researchers might someday use them to explore. That’s part of the lasting value of a biorepository: samples collected years ago can take on new scientific value as technologies advance and researchers ask new questions.
ACP continues to make Repository samples and linked data available to researchers investigating emerging questions in MS, extending the impact of contributions made by research participants years ago — and enabling new discoveries today and beyond.
Read the new study →
Read the earlier review →
Explore ACP resources for researchers →
