Compartmentalized Inflammation in MS – A Focus on Fibroblasts
Funding Amount
$600,000
Affiliation(s)
University of Toronto
Geographic Region(s) / Province(s)
Ontario
Researcher(s)
Hot Topic(s)
Progressive MS
Research Priorities
Progressive MS
Impact Goal(s)
Understand and Halt Disease Progression
Summary:
This project aims to uncover novel mediators of ‘compartmentalized inflammation’, a process thought to contribute to disability progression in MS. Dr. Gommerman and team will examine a type of cell called fibroblasts and their interaction with specific immune cells termed Tertiary Lymphoid Tissues (TLT) in driving the process of ‘compartmentalized inflammation’ in the central nervous system (CNS). This research will further our understanding of underlying processes involved in MS progression and aims to identify new therapeutic targets that could potentially halt progression in MS.
Investigators:
Dr. Jennifer Gommerman, University of Toronto
Dr. Alexandre Prat, Centre de Recherche du CHUM
Project Description:
Further research is needed to understand the potential role of chronic compartmentalized inflammation in driving disability progression in MS. This type of inflammation takes place behind the protective blood brain barrier in the central nervous system (CNS), where it is difficult to treat with current disease-modifying therapies. Compartmentalized inflammation is thought to play a key role in the processes underlying progressive forms of MS.
This project aims to advance our understanding of the mechanisms involved in progressive MS and compartmentalized inflammation. Specifically, this project will examine the interaction between fibroblasts and immune cell aggregates termed Tertiary Lymphoid Tissues (TLT). TLTs are found near areas of nerve fibre coating damage called demyelination, and are thought to be associated with accelerated disease progression. Studies from other autoimmune diseases have shown that fibroblasts are involved in TLT formation, maturation, and maintenance. However, little is known on how fibroblasts support TLT formation in the MS brain, which the team plans to investigate.
The team will use high dimensional techniques to look at brain tissue from human MS brains and from MS-like animal models to identify molecular interactions between immune cells and fibroblasts associated with the establishment and maintenance of TLT. It will also validate the molecular targets identified, and then use blocking agents to known and novel pathways to determine their effect on eliminating TLT in animal models.
Potential Impact: Currently there are no therapeutics that can effectively stop MS progression. Increasing evidence points towards ‘compartmentalized inflammation’ as a major mechanism driving progression in MS. Further understanding of molecular mediators that cause and promote compartmentalized inflammation will be important in uncovering new therapeutic targets that can potentially stop MS progression.
Project Status: In Progress
*This research is funded in partnership with the National MS Society (US). MS Canada and the National MS Society (US) are providing $300,000 USD each, for a total of $600,000 USD in support of this research.