A new study shows that blocking a molecule that disrupts the immune system led to 50% reduction of multiple sclerosis in a mouse model of the disease.
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.
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.
In various tests in the lab and with mice, they found if they blocked the interaction of MCAM with the protein that it normally binds to, they could decrease the disease’s activity, as Prof. Prat explains:
“We observed a decrease of approximately 50% of the disease in mice with experimental autoimmune encephalomyelitis (EAE), the most widely used animal model of MS. What is especially significant is that we can stop the disease from the first symptoms in addition to having an impact on its progression, which is a first.”
For the study, Prof. Prat’s team collaborated with a private company called Prothena Biosciences, based in San Francisco, CA. The company has developed a drug called PRX003 that is designed to block MCAM and thus stop the destructive white blood cells traversing the blood-brain barrier.
Prothena is planning to start clinical trials of its experimental drug in healthy volunteers by the end of June this year. They also hope to start another trial, in patients with psoriasis, next year.
Meanwhile, Medical News Today recently reported another study, published in the journal Nature, where researchers found drugs for athlete’s foot and eczema may reverse MS.
Led by Case Western University, Cleveland, OH, the study suggests two nonprescription medications – miconazole and clobetasol – may hold the key to reversing the nerve damage sustained in patients with MS.