Targeting DICAM, a novel mediator of neuroinflammation, to treat MS

Principal Investigator: Dr. Alexandre Prat

Affiliation: Centre de Recherche du Centre Hospitalier de l’Université de Montréal

Year awarded: 2018-2019

Amount Awarded: $360,000

Keywords: Blood-Brain Barrier, DICAM, biomarker

Summary:

  • The blood-brain barrier (BBB) is a network of cells that line all the blood vessels in the brain, preventing harmful substances such as bacteria and toxins from entering the brain and spinal cord. The BBB is compromised and becomes leaky in multiple sclerosis (MS), allowing white blood cells from the immune system to pass through the barrier and enter the Central Nervous System (CNS).
  • Targeting molecular players regulating the BBB in MS can potentially halt MS in its tracks.
  • The research team will:
    • Characterize a molecule (DICAM) that regulates migration of immune cells across BBB
    • Identify the interactions between DICAM and immune cells associated with MS
    • Establish anti-DICAM as a biomarker of inflammatory immune cells in MS

Project Description:

The brain is not easily accessible to cells of the immune system, as it is surrounded by a relatively impenetrable wall of cells called the BBB. However, in MS, a large number of immune cells are able to cross this barrier, leading to the formation of brain lesions. In his previous grant, also supported by the MS Society, Dr. Alexandre Prat and his team identified a molecule, called DICAM, that regulates the migration of cells across the BBB and is increased in people with relapsing-remitting MS compared to healthy donors. Furthermore, the data revealed that DICAM is expressed on a type of white blood cells called T helper 17 cells (Th17), which are the leading agents of inflammation in the central nervous system. In order to target DICAM as a potential intervention in people with MS, it is pivotal to also understand whether DICAM plays a role in the migration of other pathogenic immune cells – forming the basis Dr. Prat’s newly funded project. In this project, Dr. Prat hopes to advance the understanding of how pathogenic immune cells enter the CNS and cause inflammation leading to lesion formation and establish a new target pathway for pharmacological intervention in MS and other inflammatory autoimmune diseases. As such this research can lead to the development of a novel treatment to halt lesion formation and thus disease progression.

Potential Impact: Develop a novel treatment that prevents harmful immune cells from crossing into the brain and spinal cord thereby halting MS disease progression.

Project Status: In Progress

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