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New treatment blocks progression of mutliple sclerosis in animal model.

A drug that could halt the progression of multiple sclerosis may soon be developed thanks to a discovery by a team at the CHUM Research Centre and the University of Montreal. The researchers have identified a molecule called MCAM and shown that blocking this molecule could delay the onset of the disease and significantly slow its progression.  The team state that they 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.  These encouraging results from in vitro tests in humans and in vivo tests in mice are published in the journal Annals of Neurology.

The researchers explain that Multiple sclerosis (MS) is a neurological disease that is characterized by paralysis, numbness, loss of vision, and gait and balance deficits that lead to chronic disability. In Canada, nearly 75,000 people have MS and there is no effective cure. They go on to add that the brain is normally protected from attacks by the blood-brain barrier. The blood-brain barrier prevents immune cells, lymphocytes, from entering the central nervous system. In people with MS, there is often leakage. Two types of lymphocytes, CD4 and CD8, find a way to cross this protective barrier. They attack the brain by destroying the myelin sheath that protects neurons, resulting in decreased transmission of nerve impulses, and plaque formation.

In 2008 the team identified a cell adhesion molecule, called MCAM (Melanoma Cell Adhesion Molecule), which plays a crucial role in dysregulation of the immune system observed in multiple sclerosis.  The previous studies showed that MCAM is necessary for the migration of CD4 and CD8 across the blood-brain barrier. It was these data finding which gave the researchers the idea to block the interaction of MCAM with the protein to which it normally binds to decrease the disease’s activity. The lab note that independently, the biotechnology company Prothena Corporation have also discovered complementary data regarding MCAM, which led to an ongoing collaboration between the CRCHUM and Prothena.

The current study 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 the disease was stopped from the first symptoms in addition to having an impact on its progression, which is a first.

MS develops in most patients in two phases, state the team. They go on to add that for 10 to 15 years, there are outbreaks of symptoms interspersed with remissions. Later, the diseases progresses and the disability worsens, leading to the use of a cane or wheelchair. Currently, none of the drugs available on the market affect the disease’s progression.

Prothena has developed a potentially disease-modifying antibody, called PRX003, which is designed to inhibit MCAM function and thus prevent migration of destructive lymphocytes into tissue. Prothena expects to initiate clinical trials of PRX003 in healthy volunteers by the end of June.

Source:  Centre hospitalier de l’Université de Montréal Research Centre (CRCHUM)

 

Cells and inflammatory mediators involved in demyelination.  Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone.  Smrtka et al 2013.
Cells and inflammatory mediators involved in demyelination. Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone. Smrtka et al 2013.

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