DICAM is a Novel Driver of Myeloid Cell Migration into the Central Nervous System in MS
- DICAM is a type of cell adhesion molecule that plays a central role in allowing the entry of pro-inflammatory immune cells into the central nervous system.
- This research aims to demonstrate that DICAM is an important therapeutic target for the treatment of relapsing and progressive forms of MS.
- The research team aims to develop humanized antibodies in order to block DICAM activity and reduce inflammation/lesion formation in MS.
Normally, the brain is not easily accessible to cells of the immune system because it is protected by the blood-brain barrier (BBB) that prevents passage of cells. However, in MS, a large number of immune cells known as monocytes and dendritic cells readily cross the BBB to infiltrate the brain which eventually leads to the formation of lesions. The movement of such aggressive immune cells from the blood to the brain is orchestrated by many factors, including cell adhesion molecules (CAMs). Dr. Alexander Prat and team have identified DICAM as a novel factor present in activated monocytes, macrophages and dendritic cells. DICAM plays a central role in allowing immune cells that can cause inflammation to cross the BBB. This research will utilize animal models of MS as well as patient-derived blood and tissue samples to show that DICAM is essential in mediating the entry of myeloid cells, which are important contributors of lesion formation in relapsing-remitting and progressive forms of MS, into the central nervous system. The team will also develop and validate a humanized antibody that targets DICAM to block its activity in order to reduce tissue damage in all forms of MS. This research aims to identify attractive treatment targets for the development of novel therapies for MS and other inflammatory diseases.
This research will provide proof of concept that DICAM is an important pharmacological target to reduce inflammation in the central nervous system and disease progression in MS. Results from this work will pave the way for new therapeutics with potential to target both relapsing-remitting and progressive forms of MS.
Project Status: Ongoing