A new study recently published in the journal Annals of Neurology revealed a potential new therapeutic strategy to halt multiple sclerosis (MS) disease progression. The study is entitled “Melanoma cell adhesion molecule–positive CD8 T lymphocytes mediate central nervous system inflammation” and was led by researchers at the Canadian Université de Montreal, the Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), and the Centre Hospitalier de l’Université de Montréal (CHUM)–Notre Dame Hospital.
MS is a progressive neurodegenerative autoimmune disorder that results from an attack on the central nervous system by the body’s own immune system, causing inflammation and damage to the myelin layer that covers and protects nerve fibers. Myelin loss leads to impairment in signal transmission along the nerve fibers, affecting motor function (like coordination, balance, speech and vision), causing irreversible neurological disability and paralysis. It is estimated that more than 2.3 million people in the world suffer from the disease. In Canada, nearly 75,000 people have MS, and in the US, it is estimated that up to 400,000 people have the disease.
The blood brain barrier protects the brain from external attacks, and it can prevent the entry of immune cells such as lymphocytes (a type of white blood cell) into the central nervous system. However, in MS patients, the blood brain barrier protection is often leaky, allowing the passage of two types of lymphocytes into the nervous system, CD4 and CD8. These lymphocytes destroy the myelin layer leading to a decrease in nerve impulse transmission.
The research team had previously discovered a cell adhesion molecule known as MCAM (melanoma cell adhesion molecule) that was found to play a key role in the deregulation of the immune system seen in MS patients. Now, using human samples and mice models, researchers discovered that the blockade of MCAM expression in lymphocytes could lead to a delay in disease onset and significantly slow disease progression.
“Our studies have shown that MCAM is necessary for the migration of CD4 and CD8 across the blood-brain barrier. If we block the interaction of MCAM with the protein to which it normally binds, we decrease the disease’s activity,” said the study’s lead author Dr. Alexandre Prat in a news release. “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.”
The team concluded that MCAM could be considered a biomarker of MS disease activity and a therapeutic target. “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,” concluded Dr. Prat.
In related news, the biotechnology company Prothena Corporation PLC also discovered new insights concerning MCAM, leading to the establishment of an ongoing collaboration between the CRCHUM and Prothena. The company developed a disease-modifying antibody (PRX003) to inhibit MCAM function and therefore prevent the migration of harmful lymphocytes into the neural tissue. Prothena plans to initiate clinical trials on PRX003 in healthy volunteers by the end of June.
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