New Drug Target Discovered for Multiple Sclerosis

A recent research shows that preventing a molecule that interrupts the immune system lead to 50% decrease of multiple sclerosis in a mouse model of the disease.

Reporting in the Annals of Neurology, investigators from the University of Montreal, explain how they identified a molecule known as MCAM (Melanoma Cell Adhesion Molecule) enables white blood cells to cross the blood-brain barrier and get into the central nervous system where they are free to cause the nerve destruction seen in multiple sclerosis.

In their paper the scientists explain promising outcomes in lab tests and a mouse model of the condition where they obstructed MCAM. They say a drug that does this in human could postpone beginning of multiple sclerosis and considerably slow its development.

Lead author Alexandre Prat, states that:

“We think we have discovered the initial therapy that will affect the quality of life of individuals with multiple sclerosis by substantially decreasing the impairment and the disease’s progression.”

There is no cure available for this autoimmune disease, it is a progressive, disabling neurological disease that results in paralysis, loss of vision, numb feeling and difficulties with balance and walking.

In many nations, MS is the major cause of nontraumatic disability in young people. While some individuals with MS experience little impairment during their life-time, as much as 60% may be having difficulties to walk unaided 20 years after onset.

It is approximated that roughly 2.2 million people worldwide are impacted by MS. In Canada, where the research took place, the disease affects more than 70,000 individuals.

Obstructing MCAM prevents immune cells crossing blood-brain barrier into the CNS

MS is an autoimmune disease, where the immune system attacks the body’s own tissue. In MS, the immune system strikes tissue in the CNS, which consists of the brain, spinal cord and the optic nerve.

Generally, the blood-brain barrier defends the CNS from attack by WBCs of the immune system. In MS, on the other hand, the blood-brain barrier leaks, enabling two types of white blood cell – CD4 and CD8 – to go over into the CNS.

These white blood cells strike the myelin sheath – the defensive insulating coating that is all around nerve cells and prevents their electrical signals leaking out. The outcome is weakened capability to transmit nerve impulses and develop of plaque along the nerve fiber.

Building on previously work, Prof. Prat and his co-workers show that CD4 and CD8 cells use MCAM like a “passport” to obtain access to the central nervous system via the blood-brain barrier.

In different tests in the laboratory and with mice, they identified if they obstructed the interaction of MCAM with the protein that it usually binds to, they could decrease the disease’s activity, as Prof. Prat describes:

“We noticed reduce of roughly 50% of the disease in mice with experimental autoimmune encephalomyelitis (EAE), the most commonly used animal design of MS. What is particularly important is that we can stop the condition from the initial symptoms in addition to having an effect on its development, which is a first.”

For the research, Prof. Prat’s team worked with a private organization known as Prothena Biosciences. The organization has developed a drug known as PRX003 that is developed to block MCAM and thus stop the dangerous white blood cells crossing the blood-brain barrier.

Prothena is planning to begin clinical studies of its experimental drug in healthy people by the end of June this year. They also wish to start another research, in individuals with psoriasis, coming year.