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Scientists discover new drug target for halting multiple sclerosis

May 20, 2015

Writing in the Annals of Neurology, researchers from the University of Montreal in Canada describe how they discovered a molecule called MCAM (Melanoma Cell Adhesion Molecule) allows white blood cells to cross the blood-brain barrier and enter the central nervous system where they are free to cause the nerve damage seen in multiple sclerosis.

In their paper the researchers describe promising results in lab tests and a mouse model of the disease where they blocked MCAM. They say a drug that does this in humans could delay onset of multiple sclerosis and significantly slow its progression.

Lead author Alexandre Prat, a neurosciences professor at Montreal, says: "We believe we have identified the first therapy that will impact the quality of life of people with multiple sclerosis by significantly reducing the disability and the disease's progression." There is no cure for multiple sclerosis (MS), a progressive, disabling neurological disease that leads to paralysis, loss of vision, numbness and difficulty with balance and walking.

In many countries, MS is the leading cause of nontraumatic disability in young adults. While some people with MS experience little disability during their lifetime, as many as 60% may be struggling to walk unaided 20 years after onset. It is estimated that as many as 2.3 million people worldwide are affected by MS. In Canada, where the study took place, the disease affects nearly 75,000 people. Blocking MCAM stops immune cells crossing blood-brain barrier into the nervous system.

MS is an autoimmune disease, where the immune system attacks the body's own tissue. In the case of MS, the immune system attacks tissue in the central nervous system, which includes the brain, spinal cord and the optic nerve. Normally, the blood-brain barrier protects the central nervous system from attack by white blood cells of the immune system. In the case of MS, however, the blood-brain barrier leaks, allowing two types of white blood cell - CD4 and CD8 - to travel over into the central nervous system.

These white blood cells attack the myelin sheath - the protective insulating coating that surrounds nerve cells and stops their electrical signals leaking out. The result is weakened ability to transmit nerve impulses and build up of plaque along the nerve fiber. Building on earlier work, Prof. Prat and his colleagues show that CD4 and CD8 cells use MCAM like a "passport" to gain entry to the central nervous system via the blood-brain barrier.

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