Unraveling Immune cell - Microglial interactions in Progressive MS
Year Awarded: 2019
Term: 5 years
Funding Amount: $1,000,000
Affiliation(s): University of Toronto
Researcher(s): Dr. Jennifer Gommerman
- Dr. Jennifer Gommerman (University of Toronto)
- Dr. Alexandre Prat (University of Montreal)
This project aims to shed light on how most people with relapsing-remitting multiple sclerosis (MS) (RRMS) transition to a secondary progressive phase of MS (SPMS) and will help explain why many of the current MS drugs are unable to effectively treat SPMS.
While there are 14 therapeutic options for individuals with RRMS, there is only one treatment conditionally approved for adults with early primary progressive MS (PPMS), and limited and less effective treatments available for active forms of SPMS. Many treatments fail to effectively treat progressive forms of MS because the systems and factors that govern MS progression from RRMS to SPMS remain unclear. For instance, current MS treatments modulate the immune system but have not been shown to be effective in treating SPMS. Researchers speculate that the failure of these drugs in the treatment of SPMS may be due to: (1) the transition of the disease from RRMS to SPMS is controlled by the central nervous system (CNS) rather than the immune system, or (2) cells from the immune system continue to contribute to SPMS disease activity, but these cells are now part of the CNS.
Dr. Gommerman and team believe that the immune system and CNS are linked and that the interaction between the two systems is what drives progression in MS. This research study will utilize multiple innovative techniques to identify immune cells in the CNS and examine how they interact with other cells in the CNS. Recent research indicates that immune cell activity in SPMS may occur in the meninges, the envelope of cerebral spinal fluid that surrounds the CNS.In this study, researchers will investigate and compare brain tissue samples from autopsies of people with SPMS and those with other forms of inflammation to pinpoint the unique characteristics, such as the composition of the immune cells and their related factors and whether they are able to penetrate the cortex, the surface of the brain. They will also assess whether the immune cells and their by-products (or signals) activate key resident cells in the brain called microglia.
In collaboration with the International Progressive MS Alliance Collaborative award recipient, Dr. Francisco Quintana from the Harvard Medical School, the team will identify and further explore the abundance of different cell types, and by-products (or molecular signals) produced within fresh MS brain tissue. These experiments will provide a comprehensive understanding of the factors activating microglia throughout the transition from RRMS to SPMS. Furthering our understanding of immune cells and their by-products can be used to identify new potential therapeutic drug targets to treat progressive forms of MS.
Project Status: In Progress