Molecule could be targeted to slow MS progression
By identifying a molecule that plays a role in multiple sclerosis, Canadian researchers have paved the way for new therapies to treat this autoimmune disease.
Multiple sclerosis (MS) can cause symptoms such as extreme fatigue, lack of coordination, vision problems, cognitive impairment and mood changes. 60% of adults with MS are between the ages of 20 and 49 and women are three times more likely than men to be diagnosed with the disease. The cause remains unknown and there is presently no cure.
The good news is that researchers at the University of Montreal Hospital Research Centre (CRCHUM) have identified a molecule named ALCAM, which, once blocked, delays the progression of the disease. Their results, obtained from in vitro human and in vivo mouse studies and published in the journal Science Translational Medicine, could lead to the development of a new generation of therapies.
Under normal conditions, the blood–brain barrier protects our brain from exposure to harmful elements; for example, it prevents cells of the immune system such as lymphocytes from invading our central nervous system. However, in people with MS this barrier is permeable; thus, a large number of lymphocytes (white blood cells) manage to migrate into the brain and deteriorate its tissues via destruction of the myelin sheath that protects the neurons and enables the transmission of nerve impulses.
Lymphocytes known as B cells have already been shown to contribute to the progressive phase of MS; certain medications, commonly known as anti-B-cell drugs, reduce its progression and the resulting disability. Now, the CRCHUM researchers have shown that the molecule ALCAM (Activated Leukocyte Cell Adhesion Molecule), expressed by B cells, controls their entry into the brain via blood vessels.
“It allows them to migrate to the other side of the blood–brain barrier in mice and humans,” said CRCHUM researcher Dr Alexandre Prat. “By blocking this molecule in mice, we were able to reduce the flow of B cells into their brains and, as a result, slow the progression of the disease.
“The molecule ALCAM is expressed at higher levels on the B cells of people with multiple sclerosis,” Dr Prat continued. “By specifically targeting this molecule, we will now be able to explore other therapeutic avenues for the treatment of this disease.”
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