Multiple sclerosis (MS) is a disease of the central nervous system (CNS) which causes circulating immune cells, called T cells, to gain access to the CNS across the blood-brain barrier. This causes inflammation, myelin destruction, and neuronal damage. MS affects over 2.5 million people world-wide and is the leading cause of disability in young adults.This disease prevents nerves from conducting the proper signals, resulting in deficiencies in movement and cognitive function. It is extremely debilitating, and at this time there is no effective treatment.
Yet, there is hope. Researchers at McGill and the University of Alberta have made a discovery that could one day be used to prevent the symptoms and progression of the disease. While examining donated human brain tissues, scientists discovered that the brains of MS patients have a high content of a protein called calnexin. Compared to the brains of healthy patients, this protein is involved in controlling the blood-brain barrier’s functioning and protein quality control. The calnexin cycle is also a McGill discovery, which was defined and collaborated on by Dr. David Thomson and Dr. John Bergeron.
The blood-brain barrier plays a critical role in many CNS diseases, including MS. This is because the barrier restricts the transfer of cells and molecules to the CNS. When certain cells like T cells, which destroy the protective covering of neurons called myelin, permeate the blood-brain barrier, it disrupts the function of the nervous system and can compromise neuronal functioning. High calnexin levels increase the ability of T cells to access the brain. These cells permeate the blood-brain barrier and attack neurons, causing brain and spinal cord inflammation and nerve damage.
The high abundance of calnexin in MS brain tissue has led scientists to believe that it must play a role in the development of the disease. Researchers induced mice with experimental autoimmune encephalomyelitis (EAE). In a breakthrough in MS research, they found that mice lacking calnexin were resistant to EAE. Luis Agellon, professor at the McGill School of Human Nutrition and one of the researchers of this study, discussed the work’s potential in creating new therapies for the disease.
“We find that mice that are lacking calnexin show complete resistance to the consequences of EAE, which by extension suggests that they don’t get MS,” Agellon said in an interview with The McGill Tribune. “This has opened the area of investigation that can produce ideas and therapies in preventing […] and treating the disease.”
Agellon also discussed the future directions that MS research can take to manipulate calnexin in order to strengthen the blood-brain barrier.
“Now that we know that calnexin is involved in the pathogenesis of MS, we can see calnexin is necessary for T cell migration into the CNS,” Agellon explained. “Removing calnexin strengthens the integrity of the barrier, which breaks down when there is MS. This allows T cells to gain access. The next step is to see how the loss of calnexin manages to strengthen the blood brain barrier.”
The prevalence of MS is two to three times higher in women than in men. Agellon highlighted research questions that could develop from this observation.
“Women are three times as likely as [men] to get MS,” Agellon said. “[Is] there something special about how cells are configured in females? Is calnexin overactive in women [permitting] the [disease’s] progression?”
Evidently, Agellon’s research is very promising. Canada has one of the highest rates of MS in the world, with one in every 330 citizens living with the disease. Research, like that conducted by McGill and the University of Alberta brings medical advancements gradually closer to developing an effective treatment for this debilitating disease.
