Multiple sclerosis (MS), believed to be an immune-mediated disorder, is the most common disabling condition of the central nervous system (CNS) affecting young adults. Infiltration of leukocytes into the brain, helped by upregulation of matrix metalloproteinases (MMPs) which cleave components of the extracellular matrix, plays a significant role in causing the demyelination and axonal degeneration associated with MS.
Synthesis of MMPs is regulated by extracellular matrix metalloproteinase inducer (EMMPRIN, CD147), a multifunctional member of the immunoglobulin superfamily, and researchers at the Hotchkiss Brain Institute, University of Calgary have shown that EMMPRIN levels are significantly increased in the brain of MS patients, particularly in plaque-containing regions. The team also showed that EMMPRIN levels are increased in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EMMPRIN was upregulated on peripheral leukocytes before the appearance of MS-like symptoms and on infiltrating leukocytes and resident cells within the CNS once clinical symptoms had developed. Treating the mice with an anti-EMMPRIN antibody reduced MMP activity, infiltration of leukocytes into the CNS, and the severity of MS-like symptoms. To be effective, the antibody had to be administered at the onset of clinical signs, a time that is typically associated with significant infiltration of leukocytes into the CNS.
The study, which is published in the Journal of Neuroscience, suggests that blocking the activity of EMMPRIN may be a novel way to treat MS.